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Caffeine is a naturally occurring xanthine derivative used as a CNS and respiratory stimulant, or as a mild diuretic. Other xanthine derivatives include the bronchodilator theophylline and theobromine, a compound found in cocoa and chocolate. Caffeine is found in many beverages and soft drinks. Caffeine is often combined with analgesics or with ergot alkaloids for the treatment of migraine and other types of headache. Caffeine is also sold without a prescription in products marketed to treat drowsiness, or in products for mild water-weight gain. Caffeine was first approved by the FDA for use in a drug product in 1938. Clinically, it is used both orally and parenterally as a respiratory stimulant in neonates with apnea of prematurity. Caffeine reduces the frequency of apneic episodes by 30—50% within 24 hours of administration.1 Caffeine is preferred over theophylline in neonates due to the ease of once per day administration, reliable oral absorption, and a wide therapeutic window. A commercial preparation of parenteral caffeine, Cafcit®, was FDA approved for the treatment of apnea of prematurity in October 1999, after years of availability only under orphan drug status (e.g., Neocaf). The FDA has continued the orphan drug status of the approved prescription formulation.


L-theanine is a water-soluble amino acid that can be found in mushrooms and green tea. Purified L-theanine is marketed as an oral dietary supplement with purported antioxidant and sedative properties. Numerous investigations conducted on animals and in vitro reveal that the compounds have lipid-lowering,  neuroprotective, antiobesity, and anticancer effects. Other laboratory research suggests L-theanine may influence neurotransmitter levels, reduce cognitive impairment brought on by beta-amyloid, and lengthen life expectancy in C. elegans.
There have been a few studies done on humans as well. Although there were good effects on sleep, there were no significant effects on anxiety in a double-blind trial of supplementary L-theanine for generalized anxiety disorder. Although bigger, well-designed trials are required, several small studies in patients with other illnesses point to benefits in sleep quality as well as a potential reduction in depression, anxiety, and cognitive deficits. Although effects seen with caffeine alone in one study were lost with concurrent L-theanine, some studies testing L-theanine with caffeine suggest increases in cognitive performance. L-theanine helped schizophrenia patients sleep better and with less anxiety when used in conjunction with antipsychotic medication.
Epidemiological evidence suggests drinking green tea may help prevent strokes, but it's not obvious if L-theanine by itself can have this effect.
According to preclinical research, doxorubicin and idarubicin's chemotherapeutic effectiveness are enhanced by L-theanine, and their side effects are reduced. However, since these effects are not supported by clinical research and epigallocatechin-3-gallate (EGCG), a compound found in green tea, decreases the efficacy of the chemotherapy medicine bortezomib, patients receiving chemotherapy should talk with their doctors before using L-theanine. 2


Dehydroepiandrosterone (DHEA) is a C19 steroid also known as 5-androsten-3 beta-ol-17-one. DHEA and DHEAS (an active, sulfated form of DHEA), are endogenous hormones secreted by the adrenal cortex in primates and a few non-primate species in response to ACTH. DHEA is a steroid precursor of both androgens and estrogens, and thus is often called 'the mother hormone'. Endogenous DHEA is thought to be important in several endocrine processes, but current medical use of DHEA is limited to controlled clinical trials. In 1997, Pharmadigm, Inc. received an orphan drug designation to enroll patients with thermal burns who require skin-grafting into trials using injectable DHEAS, known as PB-005. Researchers continue to investigate the role of both endogenous and exogenous DHEA in CNS, psychiatric, endocrine, gynecologic and obstetric, immune, and cardiovascular functions.3 GeneLabs Technologies, Inc., submitted an NDA in September 2000 for its proprietary DHEA product, called prasterone (Prestara™, formerly known Aslera™ or GL-701). Prasterone appears to attentuate some symptoms of mild-to-moderate systemic lupus erythematosus (SLE) and may increase bone density based on evidence from two phase III studies in women; studies in men with SLE are ongoing. The FDA placed Prestara™ under a 6-month priority review status in October 2000; on April 19, 2001 the FDA stated that although the drug showed advantages over placebo in one study, the advantages were not statistically significant. Additional data were submitted to the FDA following a 'not approvable' letter on June 26, 2001. On September 2, 2002, the FDA issued an 'approvable' letter for the Prestara™ product, but the agency has asked for additional clinical trial data regarding the drug's effects on bone mineral density before granting final approval for SLE. The manufacturer began a confirmatory phase III trial in early 2003; the primary endpoint will be measurement of bone mineral density of the lumbar spine; the trial is targeted for completion at the end of 2003. In October 2004, the manufacturer released information that Prestara™ therapy did not meet the primary end point in the confirmatory trial. In August 2003, Paladin Labs Inc., received orphan drug designation from the FDA for prasterone, dehydroepiandrosterone, DHEA, under the brand name Fidelin™, for adrenal insufficiency.

Exogenously administered DHEA is sold as a nutritional supplement in health and drug stores and many older individuals are using it to 'maintain the vitality of their youth'. There is currently no objective, well-controlled, large-scale, scientific evidence to back claims that taking DHEA combats the signs or symptoms of aging, diabetes, neurologic disease, sexual dysfunction, or heart disease.4 Some athletes abuse DHEA believing that it can enhance the body's synthesis of testosterone; the potential action of DHEA as an anabolic steroid has lead to the prohibition of supplementation in competitive sport, even though evidence of anabolic effects in athletes is lacking.5 DHEA is also abused by athletes in an attempt to normalize the testosterone:epitestosterone ratio. However, the sensitivity and specificity of currently available testing for athletic 'doping' can readily identify the presence of banned substances, including testosterone. Because of DHEA's complex physiologic actions, more than 500 scientific articles investigating it have been published since 1993. Many of the short-term trials of DHEA to date have lacked the rigor and statistical applications needed to support therapeutic claims. Most claims will need to be confirmed by large-scale, properly conducted, and controlled studies. In 1984, the FDA banned the non-prescription (OTC) sale of exogenous DHEA due to concern over hepatotoxicity (hepatitis and hepatic tumors) as noted in animal studies. The FDA formally relegated DHEA to a Category II OTC ingredient at that time (i.e., not generally recognized as safe and effective). However in 1994, the passage of the US Dietary Supplement Health and Education Act (DSHEA) allowed DHEA to be marketed as a nutritional or dietary supplement.


Inositol is a family of cyclic sugar alcohols consisting of nine stereoisomers of hexahydroxycyclohexane. The stereoisomers of the inositol family are myo-, scyllo-, muco-, neo-, allo-, epi-, cis-, and the enantiomers L- and D-chiro-inositol. Of these, myo-inositol and D-chiro-inositol are among the most abundant biologically active forms. The enzyme epimerase converts myo-inositol to the D-chiro-inositol isomer, maintaining organ-specific ratios of the two isomers. Physiologically, the concentration of myo-inositol is several times higher than D-chiro-inositol in most tissues.6

The myo-inositol derivative phosphatidylinositol is an important component of the lipid bilayer of cell membranes. Phosphatidylinositol and its phosphorylated forms act as second messengers that are involved in a host of cellular functions including membrane trafficking, autophagy, cell migration, and survival. Disruption of phosphoinositide lipid signaling is implicated in cancer, diabetes, and cardiovascular disorders.7

Inositol has shown clinical benefits in treating disorders associated with metabolic syndrome. Inositol supplementation has been effectively used to accelerate weight loss, reduce fat mass,8 improve serum lipid profiles and upregulate the expression of genes involved in lipid metabolism and insulin sensitivity9 in women with polycystic ovarian syndrome. Myo-inositol alone or in combination with D-chiro-inositol significantly reduced weight, BMI, and waist-hip circumference ratios in overweight/obese women with PCOS. Weight loss, reduction in fat mass and increase in lean mass were accelerated when inositol supplementation was accompanied by a low-calorie diet.10 In addition, inositol supplementation was associated with lower rate of gestational diabetes and preterm delivery in pregnant women.8 Currently, research is being performed to assess whether inositol may be used in treating various cancers.


Methionine is a sulfur-containing branched-chain amino acid. A precursor for cellular methylation reactions, methionine plays an important role in lipid metabolism, polyamine synthesis, immune function, heavy metal chelation, and maintenance of redox balance.11 Conversely, dietary methionine restriction in rodents increased energy expenditure, improved insulin resistance, and enhanced lipolysis and fatty acid oxidation in adipose tissue.12

The lipotropic effects of methionine may be attributed to its metabolite S-adenosyl methionine (SAM). SAM is synthesized from methionine via an energy-consuming reaction. SAM administered orally or by injection has been investigated as a treatment for liver diseases, osteoarthritis, and depression.13 The benefits bestowed by SAM may be due to its role as a methyl donor in biochemical processes governing lipid homeostasis, DNA stability, gene expression, and neurotransmitter release.141516


Methylcobalamin, or vitamin B12, is a B-vitamin. It is found in a variety of foods such as fish, shellfish, meats, and dairy products. Although methylcobalamin and vitamin B12 are terms used interchangeably, vitamin B12 is also available as hydroxocobalamin, a less commonly prescribed drug product (see Hydroxocobalamin monograph), and methylcobalamin. Methylcobalamin is used to treat pernicious anemia and vitamin B12 deficiency, as well as to determine vitamin B12 absorption in the Schilling test. Vitamin B12 is an essential vitamin found in the foods such as meat, eggs, and dairy products. Deficiency in healthy individuals is rare; the elderly, strict vegetarians (i.e., vegan), and patients with malabsorption problems are more likely to become deficient. If vitamin B12 deficiency is not treated with a vitamin B12 supplement, then anemia, intestinal problems, and irreversible nerve damage may occur.

The most chemically complex of all the vitamins, methylcobalamin is a water-soluble, organometallic compound with a trivalent cobalt ion bound inside a corrin ring which, although similar to the porphyrin ring found in heme, chlorophyll, and cytochrome, has two of the pyrrole rings directly bonded. The central metal ion is Co (cobalt). Methylcobalamin cannot be made by plants or by animals; the only type of organisms that have the enzymes required for the synthesis of methylcobalamin are bacteria and archaea. Higher plants do not concentrate methylcobalamin from the soil, making them a poor source of the substance as compared with animal tissues.

Naltrexone HCl

Naltrexone is an oral opiate receptor antagonist. It is derived from thebaine and is very similar in structure to oxymorphone. Like parenteral naloxone, naltrexone is a pure antagonist (i.e., agonist actions are not apparent), but naltrexone has better oral bioavailability and a much longer duration of action than naloxone. Clinically, naltrexone is used to help maintain an opiate-free state in patients who are known opiate abusers. Naltrexone is of greatest benefit in patients who take the drug as part of a comprehensive occupational rehabilitative program or other compliance-enhancing program. Unlike methadone or LAAM, naltrexone does not reinforce medication compliance and will not prevent withdrawal. Naltrexone has been used as part of rapid and ultrarapid detoxification techniques. These techniques are designed to precipitate withdrawal by administering opiate antagonists. These approaches are thought to minimize the risk of relapse and allow quick initiation of naltrexone maintenance and psychosocial supports. Ultrarapid detoxification is performed under general anesthesia or heavy sedation. While numerous studies have been performed examining the role of these detoxification techniques, a standardized procedure including appropriate medications and dose, safety, and effectiveness have not been determined in relation to standard detoxification techniques.17 Naltrexone supports abstinence, prevents relapse, and decreases alcohol consumption in patients treated for alcoholism. Naltrexone is not beneficial in all alcoholic patients and may only provide a small improvement in outcome when added to conventional therapy. The FDA approved naltrexone in 1984 for the adjuvant treatment of patients dependent on opiate agonists. FDA approval of naltrexone for the treatment of alcoholism was granted January 1995. The FDA approved Vivitrol, a once-monthly intramuscular naltrexone formulation used to help control cravings for alcohol in April 2006, and then in October 2010, the FDA approved Vivitrol for the prevention of relapse to opioid dependence after opioid detoxification.

Phentermine HCl

Phentermine is an oral sympathomimetic amine used as an adjunct for short-term (e.g., 8—12 weeks) treatment of exogenous obesity. The pharmacologic effects of phentermine are similar to amphetamines. Phentermine resin complex was approved by the FDA in 1959, but is no longer marketed in the US. Phentermine hydrochloride was FDA approved in 1973. In the mid-90s, there was renewed interest in phentermine in combination with another anorectic, fenfluramine, for the treatment of obesity and substance abuse, however, little scientific data support this practice. On July 8, 1997, the FDA issued a 'Dear Health Care Professional' letter warning physicians about the development of valvular heart disease and pulmonary hypertension in women receiving the combination of fenfluramine and phentermine; fenfluramine was subsequently withdrawn from the US market in fall of 1997. Use of phentermine with other anorectic agents for obesity has not been evaluated and is not recommended. In May 2011, the FDA approved a phentermine hydrochloride orally disintegrating tablet (Suprenza) for the treatment of exogenous obesity.18

Yohimbine HCl

Yohimbine is an oral alpha-2 blocker that is chemically related to reserpine. It is an alkaloid found in the bark of Rubiaceae and related trees, but can also be found in Rauwolfia serpentina. Yohimbine has been proposed as a treatment for erectile dysfunction (ED), however only limited evidence exist. According to ED treatment guidelines, only one small study in the published literature used acceptable efficacy outcome measures; therefore, conclusions about the clinical efficacy of yohimbine have not been established and its use in the treatment of ED is not recommended. Further, associated adverse events such as elevations of blood pressure and heart rate, increased motor activity, irritability, and tremor may limit its use.1920 Yohimbine has been available since before 1938.


  • Scanlon JEM, Chin KC, Morgan MEI, et al. Caffeine or theophylline for neonatal apnea? Arch Dis Child 1992;67:425-8.

  • 2.L-Theanine. Memorial Sloan Kettering Cancer Center. (n.d.). Retrieved July 8, 2022, from

  • 3.Kroboth PD, Slalek FS, Pittenger AL et al. DHEA and DHEA-S: a review. J Clin Pharmacol 1999;39:327-348.

  • 4.Skolnick AA. Medical news and perspectives-scientific verdict still out on DHEA. JAMA 1996;276:1365-1367.

  • 5.Kreider RB. Dietary supplements and the promotion of muscle growth with resistance exercise. Sports Med 1999;27:97-110.

  • 6.Kalra, B., Kalra, S. & Sharma, J. B. The inositols and polycystic ovary syndrome. Indian J. Endocrinol. Metab. 20, 720–724 (2016).

  • 7.Bizzarri, M., Fuso, A., Dinicola, S., Cucina, A. & Bevilacqua, A. Pharmacodynamics and pharmacokinetics of inositol(s) in health and disease. Expert Opinion on Drug Metabolism and Toxicology vol. 12 1181–1196 (2016).

  • 8.Donne, M. L. E., Metro, D., Alibrandi, A., Papa, M. & Benvenga, S. Effects of three treatment modalities (diet, myoinositol or myoinositol associated with D-chiro-inositol) on clinical and body composition outcomes in women with polycystic ovary syndrome. Eur. Rev. Med. Pharmacol. Sci. 23, 2293–2301 (2019).

  • 9.Shokrpour, M. et al. Comparison of myo-inositol and metformin on glycemic control, lipid profiles, and gene expression related to insulin and lipid metabolism in women with polycystic ovary syndrome: a randomized controlled clinical trial. Gynecol. Endocrinol. 35, 406–411 (2019).

  • 10.Effects of three treatment modalities (diet, myoinositol or myoinositol associated with D-chiro-inositol) on clinical and body composition outcomes in women with polycystic ovary syndrome.

  • 11.Martínez, Y. et al. The role of methionine on metabolism, oxidative stress, and diseases. Amino Acids vol. 49 2091–2098 (2017).

  • 12.Zhou, X. et al. Methionine restriction on lipid metabolism and its possible mechanisms. Amino Acids vol. 48 1533–1540 (2016).

  • 13.S-Adenosyl-L-Methionine (SAMe): In Depth | NCCIH.

  • 14.Chiang, P. K. et al. S‐Adenosylmetliionine and methylation. FASEB J. 10, 471–480 (1996).

  • 15.Obeid, R. & Herrmann, W. Homocysteine and lipids: S-Adenosyl methionine as a key intermediate. FEBS Letters vol. 583 1215–1225 (2009)

  • 16.Sharma, A. et al. S-adenosylmethionine (SAMe) for neuropsychiatric disorders: A clinician-oriented review of research. Journal of Clinical Psychiatry vol. 78 e656–e667 (2017).

  • 17.O'Connor PG, Kosten TR. Rapid and ultrarapid opioid detoxification techniques. JAMA 1998;279:229-234.

  • 18.Suprenza (phentermine hydrochloride) package insert. Cranford, NJ: Akrimax Pharmaceuticals; 2011 Oct.

  • 19.Montague DK, Jarow JP, Broderick GA, et al. Chapter 1: The management of erectile dysfunction: an AUA update. J Urol 2005;174:230-9.

  • 20.Lebret T, Herve JM, Gorny P, et al. Efficacy and safety of a novel combination of L-arginine glutamate and yohimbine hydrochloride: a new oral therapy for erectile dysfunction. Eur Urol 2002;41:608-13.

  • 21.Araneo BA, Ryu SY, Barton S, et al. Dehydroepiandrosterone reduces progressive dermal ischemia caused by thermal injury. J Surg Res 1995;59:250-262.

  • 22.Jesse Rl, Loesser K, Eich DM, et al. Dehydroepiandrosterone inhibits human platelet aggregation in vitro and in vivo. Ann N Y Acad Sci 1995;774:281-290.

  • 23.25801

  • 24.Ortmeyer, H. K. Dietary myoinositol results in lower urine glucose and in lower postprandial plasma glucose in obese insulin resistant rhesus monkeys. Obes. Res. 4, 569–575 (1996).

  • 25.Pintaudi, B., Di Vieste, G. & Bonomo, M. The Effectiveness of Myo-Inositol and D-Chiro Inositol Treatment in Type 2 Diabetes. Int. J. Endocrinol. 2016, (2016).

  • 26.Fan, C. et al. Effects of D-Chiro-Inositol on Glucose Metabolism in db/db Mice and the Associated Underlying Mechanisms. Front. Pharmacol. 11, 354 (2020).

  • 27.Bevilacqua, A. & Bizzarri, M. Inositols in insulin signaling and glucose metabolism. International Journal of Endocrinology vol. 2018 (2018).

  • 28.Kenney, J. L. & Carlberg, K. A. The effect of choline and myo-inositol on liver and carcass fat levels in aerobically trained rats. Int. J. Sports Med. 16, 114–116 (1995).

  • 29.Andersen, D. B. & Holub, B. J. The relative response of hepatic lipids in the rat to graded levels of dietary myo-inositol and other lipotropes. J. Nutr. 110, 496–504 (1980).

  • 30.Shimada, M., Hibino, M. & Takeshita, A. Dietary supplementation with myo-inositol reduces hepatic triglyceride accumulation and expression of both fructolytic and lipogenic genes in rats fed a high-fructose diet. Nutr. Res. 47, 21–27 (2017).

  • 31.Mato, J. M., Martínez-Chantar, M. L. & Lu, S. C. S-adenosylmethionine metabolism and liver disease. Annals of Hepatology vol. 12 183–189 (2013).

  • 32.Elshorbagy, A. K. et al. S-Adenosylmethionine Is Associated with Fat Mass and Truncal Adiposity in Older Adults. J. Nutr. 143, 1982–1988 (2013).

  • 33.Yue, T., Fang, Q., Yin, J., Li, D. & Li, W. S-adenosylmethionine stimulates fatty acid metabolism-linked gene expression in porcine muscle satellite cells. Mol. Biol. Rep. 37, 3143–3149 (2010).

  • 34.Da Silva, R. P., Nissim, I., Brosnan, M. E., Brosnan, J. T. & Labrador, C. ; Creatine synthesis: hepatic metabolism of guanidinoacetate and creatine in the rat in vitro and in vivo. Am J Physiol Endocrinol Metab 296, 256–261 (2009).

  • 35.Adipex-P (phentermine hydrochloride tablets and capsules) package insert. Sellersville, PA: Teva Pharmaceuticals; 2013 Jan.

  • 36.Zolkowska D, Rothman RB, Baumann MH. Amphetamine analogs increase plasma serotonin: implications for cardiac and pulmonary disease. J Pharmacol Exp Ther. 2006;318:604-610.

  • 37.Cafcit (caffeine citrate) package insert. Eatontown, NJ: West-Ward Pharmaceuticals; 2019 Dec.

  • 38.Charles BG, Townsend SR, Steer PA, et al. Caffeine citrate treatment for extremelypremature infants with apnea: population pharmacokinetics, absolute bioavailability, and implications for therapeutic drug monitoring. Ther Drug Monit 2008; 30:709–16

  • 39.Sawynok J, Yaksh T. Caffeine as an Analgesic Adjuvant: A Review of Pharmacology and Mechanisms of Action. Pharmacol Rev 1993; 45(1): 43 - 85.

  • 40.Hansten PD, Horn JR. Cytochrome P450 Enzymes and Drug Interactions, Table of Cytochrome P450 Substrates, Inhibitors, Inducers and P-glycoprotein, with Footnotes. In: The Top 100 Drug Interactions - A guide to Patient Management. 2008 Edition. Freeland, WA: H&H Publications; 2008:142-157.

  • 41.Spitzer AR. Evidence-Based Methylxanthine Use in the NICU. Clin Perinatol 2012. 39: 127-148.

  • 42.Aldridge A, Aranda JV, Neims AH. Caffeine metabolism in the newborn. Clin Pharmacol Ther; 1979 25(4):447-53.

  • 43.Al-Alaiyan S, Al-Rawithi S, Raines D et al. Caffeine Metabolism in Premature Infants. Journal of Clinical Pharmacology; 2001 41(6): 620-7.

  • 44.Lee T, Charles B, Steer P, et al. Population pharmacokinetics of intra-venous caffeine in neonates with apnea of prematurity. Clin Pharmacol Ther. 1997;61:628–640.

  • 45.Pearlman SA, Duran C, Wood MA, et al. Caffeine pharmacokinetics in preterm infants older than 2 weeks. Dev Pharmacol Ther 1989;12:65–9.

  • 46.  Scheid, L., Ellinger, S., Alteheld, B., Herholz, H., Ellinger, J., Henn, T., Helfrich, H.-P., & Stehle, P. (2012, October 24). Kinetics of L-theanine uptake and metabolism in healthy participants are comparable after ingestion of L-theanine via capsules and green tea. OUP Academic. Retrieved July 11, 2022, from

  • 47.Parasrampuria J, Schwartz K, Petesch R. Quality control of dehydroepiandrosterone dietary supplement products. JAMA 1998;280:1565.

  • 48.Dinicola, S. et al. Nutritional and acquired deficiencies in inositol bioavailability. Correlations with metabolic disorders. International Journal of Molecular Sciences vol. 18 (2017).

  • 49.DAUGHADAY, W. H. & LARNER, J. The renal excretion of inositol in normal and diabetic human beings. J. Clin. Invest. 33, 326–332 (1954).

  • 50.Phelps, D. L. et al. Safety and pharmacokinetics of multiple dose myo-inositol in preterm infants. Pediatr. Res. 80, 209–217 (2016).

  • 51.Kuang, Y., Wang, F., Corn, D. J., Tian, H. & Lee, Z. In vitro characterization of uptake mechanism of L-[methyl- 3H]-methionine in hepatocellular carcinoma. Mol. Imaging Biol. 16, 459–468 (2014).

  • 52.Parkhitko, A. A., Jouandin, P., Mohr, S. E. & Perrimon, N. Methionine metabolism and methyltransferases in the regulation of aging and lifespan extension across species. Aging Cell vol. 18 (2019).

  • 53.Tidwell, H. C., Slesinski, F. A. & Treadwell, C. R. Methionine Excretion. Effect of Diet and Methionine Ingestion in Normal Subjects. Exp. Biol. Med. 66, 482–485 (1947).

  • 54.Le Corre P, Parmer RJ, Kailasam MT, et al: Human sympathetic activation by alpha2-adrenergic blockade with yohimbine: Bimodal, epistatic influence of cytochrome P450-mediated drug metabolism. Clin Pharmacol Ther 2004;76(2):139-153.

  • 55.Bharucha AE, Skaar T, Andrews CN, et al. Relationship of cytochrome P450 pharmacogenetics to the effects of yohimbine on gastrointestinal transit and catecholamines in healthy subjects. Neurogastroenterol Motil 2008;20: 891–9.

  • 56.Bhatia J. Current options in the management of apnea of prematurity. Clin Pediatr 2000;39:327-36.

  • 57.Erenberg A, Leff RD, Haack DG, et al. Caffeine Citrate for the Treatment of Apnea of Prematurity: A Double-Blind, Placebo-Controlled Study. Pharmacotherapy 2000;20(6):644–652.

  • 58.Kaltenbach T, Crockett S, Gerson LB. Are lifestyle measures effective in patients with gastroesophageal reflux disease? An evidence-based approach. Arch Intern Med. 2006;166:965-971.

  • 59.Christian MS, Brent RL. Teratogen update: evaluation of the reproductive and developmental risks of caffeine. Teratology 2001;64:51-78.

  • 60.Hadeed A, Siegel S. Newborn cardiac arrhythmias associated with maternal caffeine use during pregnancy. Clin Pediatr 1993;32:45-7.

  • 61.American Academy of Pediatrics (AAP) Committee on Drugs. Transfer of drugs and other chemicals into human milk. Pediatrics 2001;108(3):776-789.

  • 62.Le Guennec JC, Billon B. Delay in caffeine elimination in breast-fed infants. Pediatrics 1987;79:264-8.

  • 63.Berlin CM, Denson HM, Daniel CH, et al. Disposition of dietary caffeine in milk, saliva, and plasma of lactating women. Pediatrics 1984;73:59-63.

  • 64.Tyrala EE, Dodson WE. Caffeine secretion into breast milk. Arch Dis Child 1979;54:787-800.

  • 65.Hill RM, Craig JP, Chaney MD, et al. Utilization of over-the-counter drugs during pregnancy. Clin Obstet Gynecol 1977;20:381-94.

  • 66.Awake (caffeine) tablet package insert. Deerfield, IL: Walgreen Co. 05/214.

  • 67.MediLexicon International. (n.d.). L-theanine: Benefits, risks, sources, and dosage. Medical News Today. Retrieved July 11, 2022, from

  • 68.Katz S, Morales AJ. Dehydroepiandrosterone (DHEA) and DHEA-sulfate (DS) as therapeutic options in menopause. Semin Reprod Endocrinol 1998;16:161-170.

  • 69.Rosenfield RL. Ovarian and adrenal function in polycystic ovary syndrome. Endocrinol Metab Clin North Am 1999;28:265-293.

  • 70.Wellman M, Shane-McWhorter L, Orlando PL et al. The role of dehydroepiandrosterone in diabetes mellitus. Pharmacotherapy 1999;19:582-591.

  • 71.Centurelli MA, Abate MA. The role of dehydroepiandrosterone in AIDS. Ann Pharmacother 1997;31:639-642.

  • 72.Naltrexone (naltrexone hydrochloride) package insert. Hazelwood, MO: Mallinckrodt, Inc. 2009 Feb.

  • 73.Vivitrol (naltrexone extended release injectable suspension) package insert. Cambridge, MA: Alkermes, Inc.; 2013 Aug.

  • 74.Revia (naltrexone hydrochloride) package insert. Pomona, NY: Duramed Pharmaceuticals, Inc. 2013 Oct.

  • 75.American Academy of Pediatrics (AAP) Committee on Drugs. Transfer of drugs and other chemicals into human milk. Pediatrics 2001;108:776-89.

  • 76.Adipex-P (phentermine hydrochloride tablets and capsules) package insert. Sellersville, PA: Teva Pharmaceuticals; 2013 Jan.

  • 77.Suprenza (phentermine hydrochloride) package insert. Cranford, NJ: Akrimax Pharmaceuticals; 2011 Oct.

  • 78.Phentermine hydrochloride package insert. Newtown, PA: KVK-Tech Inc; 2010 April.

  • 79.Steiner E, Villen T, Hallberg M, et al. Amphetamine secretion in breast milk. Eur J Clin Pharmacol 1984;27:123-4.

  • 80.Yocon (yohimbine hydrochloride, USP) package insert. Englewood, NJ: Glenwood, LLC; 2003, Jan.

  • 81.Leaf Group. (n.d.). Is L-theanine safe while pregnant? | livestrong. LIVESTRONG.COM. Retrieved July 11, 2022, from[/fn]



  • 82.Isabella, R. & Raffone, E. Does ovary need D-chiro-inositol? J. Ovarian Res. 5, 1–5 (2012).

  • 83.Rees, W. D., Wilson, F. A. & Maloney, C. A. Sulfur amino acid metabolism in pregnancy: The impact of methionine in the maternal diet. in Journal of Nutrition vol. 136 1701–1705 (American Institute of Nutrition, 2006).

  • 84. Integrative medicine. ScienceDirect. (n.d.). Retrieved July 11, 2022, from

  • 85.Vitagliano, A. et al. Inositol for the prevention of gestational diabetes: a systematic review and meta-analysis of randomized controlled trials. Archives of Gynecology and Obstetrics vol. 299 55–68 (2019).

  • 86.Nawrot P, Jordan S, Eastwood J, et al: Effects of caffeine on human health. Food Addit Contam 2003;20:1-30.

  • 87.Schmidt B, Roberts RS, Davis P, et al. Caffeine Therapy for Apnea of Prematurity. N Engl J Med 2006; 354:2112-2121.

  • 88.lane AJ, Coombs RC, et al. Effect of caffeine on neonatal splanchnic blood flow. Arch Dis Child Fetal Neonatal Ed 1999;80:F128–F129.

  • 89.Bhatt-Mehta V, Schumacher RE. Treatment of apnea of prematurity. Pediatr Drugs 2003;5:195-210.

  • 90.Caffeine tablets alertness aid supplement (product label). Woonsocket RI, CVS; 2012.

  • 91.Pollak C, Bright D. Caffeine consumption and weekly sleep patterns in US seventh-, eighth-, and ninth-graders. Pediatrics 2003;111:42-46.

  • 92.Davis R, Osorio I: Childhood caffeine tic syndrome. Pediatrics 1998;101:E4.

  • 93.Prolab Caffeine supplement product label. Chatsworth, CA Prolab Nutrition Inc; 2012.

  • 94.Integrative medicine. ScienceDirect. (n.d.). Retrieved July 11, 2022, from

  • 95.VanVollenhoven RF, Engleman EG, McGuire JL. Dehydroepiandrosterone in systemic lupus erythematosus. Arthritis Rheum 1995;38:1826-1831.

  • 96.Helzlsouer KJ, Alberg AJ, Gordon GB, et al. Serum gonadotropins and steroid hormones and the development of ovarian cancer. JAMA 1995;274:1926-1930.

  • 97.Jones JA, Nguyen A, Straub M, et al. Use of DHEA in a patient with advanced prostate cancer: a case report and a review. Urology 1997;50:784-788.

  • 98.Singh, P. (2018, October 17). Methionine drug information - indications, dosage, side effects and precautions. Medindia. Retrieved June 29, 2022, from 

  • 99.Vivitrol (naltrexone extended release injectable suspension) package insert. Waltham, MA: Alkermes, Inc.; 2021 Mar.

  • 100.Suprenza (phentermine hydrochloride) package insert. Cranford, NJ: Akrimax Pharmaceuticals; 2011 Oct.

  • 101.Phentermine hydrochloride package insert. Newtown, PA: KVK-Tech Inc; 2010 April.

  • 102.Lomaira (phentermine hydrochloride) package insert. Newton, PA: KVK-Tech, Inc.; 2016 Sept.

  • 103.Hendricks EJ, Srisurapanont M, Schmidt SL, et al. Addiction potential of phentermine prescribed during long-term treatment of obesity. Int J Obes (Lond). 2014;38:292-298.

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