IngredientsCypionic acid, also known as cyclopentylpropionic acid, is an aliphatic carboxylic acid with the molecular formula C8H14O2. Its salts and esters are known as cypionates or cipionates. The compound's preferred IUPAC name is 3-cyclopentylpropanoic acid; it is also registered under the synonyms cyclopentanepropionic acid, cyclopentanepropaanoic acid, and 3-cyclopentylpropionic acid. Its CAS Registry Number is 140-77-2 and its EINECS number is 205-433-0.
According to ChEBI, cypionic acid is a monocarboxylic acid that is propionic acid in which one of the methyl hydrogens is substituted by a cyclopentyl group. Structurally, it consists of a five-membered carbocyclic (cyclopentyl) ring attached via a two-carbon methylene bridge (–CH2–CH2–) to a terminal carboxylic acid group (–COOH). Its canonical SMILES notation is C1CCC(C1)CCC(=O)O and its InChIKey is ZRPLANDPDWYOMZ-UHFFFAOYSA-N.
Physical data for cypionic acid include: molecular formula C8H14O2, molar mass 142.2 g/mol, density 0.996 g/mL at 25 °C, melting point 131 °C, boiling point 130–132 °C at 12 mmHg, flash point 116 °F, and the compound is insoluble in water.
The presence of the cyclopentyl ring imparts unique steric and electronic properties that differentiate it from other similar compounds. Its specific branching at the propionic position allows for distinct reactivity patterns not observed in linear or differently substituted fatty acids.
The NIH Office of Dietary Supplements' Dietary Supplement Label Database (DSLD) lists cypionic acid under the ingredient category "Non-nutrient/non-botanical," with the related label term "Cypionate ester," and notes no scientific resources (N/A) for the ingredient. This classification is significant: it means cypionic acid does not belong to the established categories of dietary nutrients (such as vitamins, minerals, amino acids, or fatty acids) nor to botanical (plant-derived) ingredients as understood by U.S. dietary supplement regulation. Its presence on some supplement labels reflects its role as a chemical modifier rather than a primary nutritional agent.
Cypionic acid is a synthetic organic compound produced by industrial chemical synthesis. No peer-reviewed literature, government database, or authoritative pharmacopeial source identifies cypionic acid as naturally occurring in plants, fungi, animals, or other biological sources. It is not extracted from botanical materials and has no documented history as a naturally occurring food constituent or phytochemical.
The synthesis of 3-cyclopentylpropionic acid typically involves the following methods: from cyclopentanone, one efficient method involves reacting cyclopentanone with alkali metal hydroxides at elevated temperatures (200–350 °C), yielding high purity and yield rates often exceeding 70%; from cyclopentanol, a similar two-step reaction involving alkali metal hydroxide under controlled temperature conditions is also employed.
A documented industrial preparation method is characterized by converting cyclopentanone or cyclopentanol in succession, in two different temperature ranges, with molten alkali hydroxide — with the temperature of the first area at 200 to 270 °C and the temperature of the second area at 290 to 350 °C — and then transferring the resulting alkali salt to cypionic acid in the free-acid form.
Additional synthesis routes in the chemical literature include alkylation of malonic acid with cyclopentyl bromide followed by decarboxylation, and hydrolysis of the corresponding cypionic acid ester.
A thorough search of authoritative sources — including WHO monographs, ESCOP monographs, German Commission E publications, the NIH National Center for Complementary and Integrative Health (NCCIH), the European Medicines Agency (EMA) herbal medicine committee (HMPC), and peer-reviewed historical pharmacognosy literature — reveals no documented traditional or historical use of cypionic acid as a dietary ingredient, herbal remedy, or folk medicine in any culture or time period.
This absence is consistent with cypionic acid's identity as an industrially synthesized compound. It should be noted that some commercial supplement marketing copy asserts a history of traditional herbal use for cypionic acid; however, such claims are unverifiable against any primary, peer-reviewed, or government sources, and they cannot be cited as credible evidence in an evidence-based reference.
The pharmaceutical relevance of cypionic acid — via its ester derivatives — dates to the mid-twentieth century, when steroid esterification chemistry was being actively developed to prolong the action of injectable hormones. This pharmaceutical history is addressed in Section 4.
The primary use of cypionic acid is in pharmaceutical formulations. Specifically, it functions as the acid component in a class of steroid ester prodrugs. Cypionic acid is used to prepare ester prodrugs which have increased half-lives relative to the parent compound.
The lipophilicity of the cypionate group allows the prodrug to be sequestered in fat depots after intramuscular injection. The ester group is slowly hydrolyzed by metabolic enzymes, releasing steady doses of the active ingredient.
The pharmacokinetic principle underlying all cypionate ester prodrugs is the same: by esterifying a hydroxyl group on the parent drug molecule with cypionic acid, the polarity of the molecule is dramatically reduced, increasing its solubility in oil vehicles and its affinity for lipid-rich tissues. Testosterone esters are less polar than free testosterone; testosterone esters in oil injected intramuscularly are absorbed slowly from the lipid phase, thus allowing testosterone cypionate to be given at intervals of two to four weeks.
Unmodified testosterone has a half-life of 10 minutes; to overcome this limitation, testosterone is esterified and then dissolved in oil to allow for sustained release into the circulation after injection. These oily solutions contain a testosterone ester dissolved in vegetable oil (usually sesame seed, tea seed, castor seed, or cottonseed oil) with some benzyl alcohol.
The slow release dynamics have been characterized pharmacokinetically. The slow release of estradiol cypionate from the tissue depot is caused by the high lipophilicity of the estradiol ester, which in turn is due to its long fatty acid cypionic acid ester moiety. Upon intramuscular injection of estradiol cypionate in an oil solution, the solvent (i.e., oil) is absorbed, and a primary microcrystalline depot is formed within the muscle at the site of injection. In addition, a secondary depot may be formed in adipose tissue.
Once the ester is released from the depot into interstitial fluid, enzymatic hydrolysis cleaves the ester bond, liberating free cypionic acid and the active parent drug. The cypionic acid moiety itself is not pharmacologically active in this context; it is a disposable chemical handle that modulates the pharmacokinetics of the active steroid.
Examples of pharmaceutical compounds prepared as cypionate esters include testosterone cypionate, estradiol cypionate, hydrocortisone cypionate, oxabolone cipionate, and mesterolone cypionate.
The mechanistic utility of cypionic acid in prodrug chemistry derives from three interrelated physicochemical properties:
Structurally, the cypionate ester group is intermediate in chain length among the commonly used steroid esters. Estradiol cypionate has a more extensive fatty acid chain and is comparatively more lipophilic than shorter-chain esters. For a given estradiol ester, the longer or more extensive the fatty acid chain is, the more lipophilic, longer-lasting, and more uniform/plateau-like the resultant levels.
It is essential to distinguish between the clinical evidence for cypionic acid itself as a dietary supplement ingredient and the extensive clinical evidence for the pharmaceutical drugs that use it as an esterification agent. No published, peer-reviewed clinical trials exist that study cypionic acid as an isolated dietary supplement ingredient in human subjects. All human clinical evidence relates to its role as a chemical component of approved pharmaceutical products.
Evidence level: Strong (for the parent pharmaceutical drug; not for cypionic acid as a supplement ingredient).
Testosterone cypionate is a synthetic androgen and anabolic steroid and hence is an agonist of the androgen receptor (AR), the biological target of androgens like testosterone and dihydrotestosterone (DHT). Testosterone cypionate is converted by the body to testosterone that has both androgenic effects and anabolic effects, which make it useful for producing masculinization and suitable for androgen replacement therapy.
Testosterone cypionate injection is indicated for replacement therapy in males associated with symptoms of deficiency or absence of endogenous testosterone, including primary hypogonadism (congenital or acquired) due to testicular failure from cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome, or orchidectomy; and hypogonadotropic hypogonadism due to gonadotropin or luteinizing hormone-releasing hormone (LHRH) deficiency, or pituitary-hypothalamic injury from tumors, trauma, or radiation.
A randomized, double-blind clinical trial was conducted to investigate long-term effects of testosterone cypionate. Thirty-one healthy men were randomized into dose groups of 100, 250, or 500 mg/week and received 14 weekly injections of testosterone cypionate. A pharmacokinetic/pharmacodynamic (PK/PD) model was developed to characterize testosterone concentrations and link exposure to changes in luteinizing hormone and spermatogenesis.
The pharmacokinetics of testosterone cypionate via depot intramuscular injection, including its elimination half-life and duration of action, are said to be extremely comparable to and hence essentially the same as those of testosterone enanthate. Other testosterone esters (cypionate, cyclohexane carboxylate) include similar pharmacokinetics, making them pharmacologically equivalent to testosterone enanthate.
Safety and efficacy of testosterone cypionate in men with "age-related hypogonadism" (also referred to as "late-onset hypogonadism") have not been established.
Evidence level: Established for the pharmaceutical compound; not studied for cypionic acid as an isolated supplement ingredient.
Estradiol esters like estradiol cypionate and estradiol valerate, when given as an injection of oil solution or microcrystalline aqueous suspension, have a relatively long duration due to the formation of an intramuscular depot from which they are slowly released and absorbed. Estradiol cypionate in combination with medroxyprogesterone acetate has been developed as a monthly injectable combined hormonal contraceptive.
No randomized controlled trials, observational cohort studies, or pharmacokinetic studies have been published in the peer-reviewed scientific literature examining cypionic acid (3-cyclopentylpropionic acid, CAS 140-77-2) administered as a standalone dietary supplement ingredient in humans. No systematic reviews, Cochrane reviews, NIH NCCIH summaries, or official monographs (WHO, ESCOP, German Commission E) address cypionic acid as a dietary supplement. The NIH DSLD entry confirms this absence by listing "Scientific Resources: N/A." Any claims of benefit for cypionic acid as a standalone supplement ingredient are not supported by verifiable scientific evidence.
Because cypionic acid has no independent clinical evidence base as a supplement ingredient, the only dosage information available in authoritative sources pertains to the pharmaceutical ester-prodrug formulations in which it participates.
No dosages for cypionic acid as an isolated oral or other dietary supplement form are reported in authoritative sources.
Given that cypionic acid's documented physiological relevance derives entirely from its role in steroid ester pharmaceuticals, the body systems implicated are those affected by the parent steroid drugs:
Safety data for cypionic acid as a standalone dietary supplement ingredient do not exist in the peer-reviewed or regulatory literature. All documented safety information pertains to the pharmaceutical prodrug formulations. The following safety considerations, drawn from authoritative FDA-approved labeling and published clinical literature, apply to cypionate ester drugs, not to cypionic acid as an independent supplement.
Side effects of testosterone cypionate include symptoms of masculinization like acne, increased hair growth, voice changes, and increased sexual desire. Testosterone supplementation is also known to reduce the threshold for aggressive behavior in men.
Prolonged use of high doses of androgens (principally the 17-alpha-alkyl-androgens) has been associated with development of hepatic adenomas, hepatocellular carcinoma, and peliosis hepatis — all potentially life-threatening complications.
Geriatric patients treated with androgens may be at an increased risk of developing prostatic hypertrophy and prostatic carcinoma, although conclusive evidence to support this concept is lacking.
There have been postmarketing reports of venous thromboembolic events, including deep vein thrombosis (DVT) and pulmonary embolism (PE), in patients using testosterone products, such as testosterone cypionate. Patients presenting with symptoms of pain, edema, warmth, and erythema in the lower extremity should be evaluated for DVT, and those presenting with acute shortness of breath should be evaluated for PE.
Androgens may increase sensitivity to oral anticoagulants; dosage of the anticoagulant may require reduction in order to maintain satisfactory therapeutic hypoprothrombinemia.
Concomitant use of corticosteroids with testosterone cypionate injection may result in increased fluid retention.
Serum cholesterol may increase during androgen therapy.
The NIH DSLD classifies cypionic acid as a "Non-nutrient/non-botanical" ingredient with no associated scientific resources. Cypionic acid has no established Dietary Reference Intake (DRI), no Daily Value (DV), no Tolerable Upper Intake Level (UL), and is not recognized as an essential nutrient by any regulatory authority including the FDA, NIH, WHO, EFSA, or EMA.
Cypionic acid's only regulatory history is as a pharmaceutical excipient and intermediate in the synthesis of FDA-regulated drug products such as testosterone cypionate (approved prior to January 1, 1982, per FDA records) and estradiol cypionate.
The evidence landscape for cypionic acid as a dietary supplement ingredient can be summarized as follows:
The overall conclusion from an evidence-based perspective is that cypionic acid, when listed as a dietary supplement ingredient on product labels, lacks any independent clinical evidence base. Its appearance in supplement labeling appears to derive from its recognized role as a chemical component of pharmaceutical ester prodrugs, but that pharmaceutical role does not translate into established efficacy or safety as a standalone dietary supplement ingredient.
Health conditions that Cypionic acid may help support.
Body systems that Cypionic acid may help support.
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