Deoxycholic acid

Deoxycholic Acid: A Comprehensive Encyclopedic Reference

1. Identity: Chemical Names, Structure, Natural Sources, and Forms

1.1 Chemical Identity

Deoxycholic acid is a bile acid. It is one of the secondary bile acids, which are metabolic byproducts of intestinal bacteria. Its formal systematic name is (4R)-4-[(3R,5R,8R,9S,10S,12S,13R,14S,17R)-3,12-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoic acid, and it is also known as 3α,12α-dihydroxy-5β-cholan-24-oic acid or, in older literature, as 3,12-dihydroxycholanic acid. The older designation "3,12-dihydroxycholanic acid" appears in early twentieth-century chemical literature, reflecting the positions of its two hydroxyl groups on the steroidal ring system. Its abbreviation in the scientific literature is DCA, and its sodium salt form is referred to as sodium deoxycholate or deoxycholate. The molecular formula is C₂₄H₄₀O₄ and the molecular weight is 392.57 g/mol.

Deoxycholate is soluble to 333 mg/mL in water, sparingly soluble in alcohol, and is even less soluble in acetone and glacial acetic acid. Reversible formation of micelles may occur with sodium deoxycholate concentrations above the critical micelle concentration of approximately 2.4 mg/mL at neutral pH.

1.2 Natural Sources and Biosynthesis

Deoxycholic acid (DCA) is a secondary bile acid produced when intestinal bacteria metabolize the primary bile acid cholic acid. The two primary bile acids secreted by the liver are cholic acid and chenodeoxycholic acid. The pathway that generates endogenous DCA is well characterized: deoxycholate biosynthesis begins with the enzymatic oxidation, isomerization, and reduction of cholesterol in the liver to form cholic acid, a bile acid structurally similar to its cholesterol parent. In the liver, cholic acid is then chemically linked to one of two amino acids (taurine or glycine) to form the conjugated cholic acids (i.e., L-glycocholate and taurocholate). These conjugated cholic acids are then stored in the gallbladder until food consumption. After food consumption, bile solution is released from the gallbladder into the intestine, where the conjugated cholic acid molecules are subject to two additional chemical modifications mediated by enzymes produced by intestinal microflora. First, conjugated cholic acid is dehydroxylated to form conjugated deoxycholate. Conjugated deoxycholate is then deconjugated to form free deoxycholate, which participates, along with the other bile acids, in the solubilization of dietary lipids.

The total bile acid pool in humans varies between 2 and 4 g normally, and the mean of its components consist of 40 percent chenodeoxycholic acid, 28 percent cholic acid, and 27 percent deoxycholic acid. The remaining 5 percent is composed largely of lithocholic acid and the 7-beta isomer of chenodeoxycholic acid, ursodeoxycholate. DCA is thus one of the most quantitatively significant bile acids in the human body.

From the small intestine, cholic acid travels to the large intestine, where specific species of gut bacteria convert it into deoxycholic acid through an eight-step chemical process. Researchers have identified six bacterial enzymes responsible for this conversion. During the process, the bacteria temporarily reshape part of the bile acid's molecular structure, using it as an energy source for their own chemistry before producing the final product.

1.3 Commercial and Pharmaceutical Sources

DCA was first isolated from ox bile in the late 1800s, then identified as a naturally occurring digestive compound in the human body. Modern cosmetic versions are produced through controlled chemical synthesis or by converting another bile acid, cholic acid, with the help of safe laboratory bacteria. The commercial injectable product Kybella is a patented formulation of a pure, nonanimal-derived version of deoxycholic acid, which is an endogenous molecule that aids in the breakdown of dietary fat. Deoxycholic acid from animals in New Zealand has historically been a source of bile acids for human use under US regulatory regimes.

1.4 Common Forms and Preparations

Deoxycholic acid is encountered in several distinct forms depending on its application:

• Endogenous free acid: The unconjugated secondary bile acid present in the human intestine and enterohepatic circulation.
• Sodium deoxycholate: The sodium salt of deoxycholic acid, often used as a biological detergent to lyse cells and solubilise cellular and membrane components.
• Injectable solution (ATX-101 / Kybella / Belkyra): A 10 mg/mL injectable formulation supplied as a clear, colorless, sterile solution in 2 mL vials intended for single patient use. Each milliliter of the solution contains 10 mg of deoxycholic acid.
• Research/laboratory reagent: In research, deoxycholic acid is used as a mild detergent for the isolation of membrane-associated proteins.

2. Historical and Traditional Use

2.1 Discovery and Early Isolation

DCA was first isolated from human fecal samples in 1911 by Fischer, though subsequent investigations focused on cholic acid and rather ignored DCA. Its structural relationship to other bile acids and steroids attracted increasing scientific attention in the first half of the twentieth century. Interest in DCA was revived in the 1940s, when it was identified as a precursor for the synthesis of corticosteroids.

2.2 Role in the Cortisone Era (1940s)

DCA achieved considerable historical significance in mid-twentieth century pharmaceutical chemistry. When it was recognized that cortisone had a C-11 oxygen atom, it was logical to use deoxycholic acid (DCA), possessing a C-12 hydroxyl group, as a chemical precursor for the synthesis of corticosteroids. DCA was easily isolated from bovine bile or synthesized from cholic acid, and it was not too difficult for a talented chemist to move the oxygen from C-12 to C-11. In 1946, H. Sarett at the Merck Company reported a complex synthesis (37 steps) of cortisone from DCA, and this led to its commercial production on a small scale. This work ultimately enabled the process research department at Merck, under the direction of Max Tishler, to perform the 37-step conversion of deoxycholic acid to cortisone on a scale that made the initial clinical trials possible. The low efficiency of converting deoxycholic acid into cortisone led to a cost of US$200 per gram in 1947. Russell Marker, at Syntex, subsequently discovered a much cheaper and more convenient starting material, diosgenin from wild Mexican yams, which eventually supplanted DCA as the principal industrial steroid precursor.

2.3 Early Medical and Food Applications

Deoxycholic acid has been used since its discovery in various fields of human medicine. In the human body, deoxycholic acid is used in the emulsification of fats for absorption in the intestine. It has, in some countries (including Switzerland), been licensed as an emulsifier in the food industry, but it is no longer common. Outside the body, it has been used on an experimental basis as a component of cholagogues and is also used to prevent and dissolve gallstones.

Since its isolation, the acid has been widely used in bacteriological media. The concept of "mesotherapy"—the use of injectables for local medical and cosmetic conditions—was originally conceived in Europe in the 1950s and was traditionally employed for pain relief, though its cosmetic applications, particularly fat and cellulite removal, later received attention.

2.4 Relationship to Traditional Medicine and Bear Bile

While deoxycholic acid itself was not isolated or specifically identified as a constituent in ancient medical traditions, the bile acids of which it is a member were present in animal-derived medicinal preparations used historically. Bear bile, containing the closely related compound ursodeoxycholic acid (UDCA), has been used in traditional Chinese medicine since the seventh century. DCA is a constituent of human and many other mammalian biles, and animal bile preparations in historical medicine would have contained DCA alongside other bile acids, though it was not specifically distinguished at those times.

3. Key Constituents, Chemistry, and Mechanisms of Action

3.1 Structure and Chemical Class

Deoxycholic acid is a C24 steroid acid belonging to the secondary bile acid family. It is distinguished from its parent molecule, cholic acid (a trihydroxy bile acid), by the absence of a hydroxyl group at the 7α position. This structural feature makes DCA more hydrophobic than cholic acid, with important consequences for its biological activity. DCA is a secondary bile acid produced when intestinal bacteria metabolize the primary bile acid cholic acid.

3.2 Role in Fat Digestion: Emulsification and Micelle Formation

In the digestive system, deoxycholic acid serves as a critical component of bile, secreted into the small intestine to aid in the emulsification of dietary fats. By breaking down large fat globules into smaller micelles, deoxycholic acid increases the surface area available for pancreatic lipases to act upon, enhancing the digestion and absorption of fats and fat-soluble vitamins. Without this emulsification step, the body would struggle to absorb fat-soluble nutrients like vitamins A, D, E, and K. Deoxycholic acid is one of several bile acids performing this job, but it is among the most abundant in the human bile acid pool.

3.3 Adipocytolytic (Cell-Lytic) Mechanism

When administered exogenously as an injectable, DCA exerts a distinct and powerful cytolytic mechanism. Synthetically derived deoxycholic acid, when injected, stimulates a targeted breakdown of adipose cells by disrupting the cell membrane and causing adipocytolysis. The mechanism by which deoxycholic acid induces adipocyte destruction is primarily through its detergent-like properties. By integrating into the lipid bilayer of the adipocyte membrane, deoxycholic acid disrupts the membrane's integrity, leading to cell rupture and death. This process not only reduces the number of fat cells in the treated area but also prevents their ability to store fat in the future.

When injected into subcutaneous fat, deoxycholic acid physically disrupts adipocyte cell membranes, leading to local adipocytolysis, cell death, and a mild, local inflammatory reaction consisting of macrophage infiltration and fibroblast recruitment. At Day 28 post-injection, inflammation largely resolves, and key histologic features include fibrotic septal thickening, neovascularization, and atrophy of fat lobules.

An important pharmacological property explains its relative tissue selectivity: physiological concentrations of albumin or protein-rich tissues decrease the ability of DC to lyse cells. Deoxycholate injected into fat tissue degrades fat cells via a cytolytic mechanism. Because deoxycholate injected into fat is rapidly inactivated by exposure to protein and then rapidly returns to the intestinal contents, its effects are spatially contained.

3.4 Receptor-Mediated Signaling: FXR and TGR5

Beyond its mechanical/detergent actions, DCA participates in complex intracellular signaling through two major bile acid receptor systems. The intestinal epithelium prominently expresses two key bile acid receptors—the farnesoid X receptor (FXR) and G protein-coupled bile acid receptor 1 (TGR5)—which play indispensable roles in maintaining bile acid homeostasis and intestinal barrier function. Next to their role in digestion of dietary fats, bile salts function as signaling molecules for bile salt receptors such as Farnesoid X receptor (FXR) and G protein-coupled bile acid receptor (TGR5). Complementary to their role in metabolism, FXR and TGR5 are shown to play a role in intestinal homeostasis and immune regulation.

In-depth mechanistic studies reveal that DCA primarily activates the Takeda G protein-coupled receptor 5 (TGR5) on the surface of intestinal epithelial and immune cells, triggering the NF-κB signaling pathway and inducing the release of pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α, while simultaneously inducing ROS bursts that lead to DNA damage.

3.5 DNA Damage and Genotoxic Potential

Deoxycholate and other secondary bile acids cause DNA damage. The molecular mechanisms underlying this property have been characterized: DCA initiates DNA damage by reactive oxygen species (ROS), production of hydroxyl radicals, and degradation of p53, triggering Poly(ADP-ribose) polymerase (PARP)-mediated DNA repair signals. The gut microbiota plays a crucial role in mediating the metabolism of primary into secondary bile acids, and recent studies have shown the DNA-damaging effect of DCA through reactive oxygen species production.

3.6 Immunomodulatory Properties

Some publications point towards the effect of deoxycholic acid as an immunostimulant of the innate immune system, activating its main actors, the macrophages. According to these publications, a sufficient amount of deoxycholic acid in the human body would correspond with a good immune reaction of the non-specific immune system. Clinical studies conducted in the 1970s and 1980s confirm the expectation that deoxycholic acid is involved in the natural healing processes of local inflammations, different types of herpes, and possibly cancer. These older findings require cautious interpretation given the limitations of studies from that era and the more complex picture that has since emerged regarding DCA's dual pro-inflammatory and carcinogenic potential.

4. Scientific Evidence by Area of Use

4.1 Submental Fat Reduction (Injectable Adipocytolysis) — Strong Clinical Evidence

This is the application for which the most rigorous human clinical evidence exists. Deoxycholic Acid (DCA) is an endogenous secondary bile acid involved in the emulsification of dietary fat before subsequent absorption in the gastrointestinal system. ATX-101 is the non-commercial name for the synthetic form of DCA and gained FDA approval in 2015 as an injectable drug for the treatment of moderate to severe submental convexity or fullness associated with submental fat. It is marketed as Kybella in the United States and Belkyra in Europe, Canada, and Australia.

Pivotal Trials: The safety and effectiveness of Kybella for treatment of submental fat were established in two clinical trials involving 1,022 adults with moderate or severe submental fat who were randomly assigned to receive either Kybella or placebo for up to six treatments. These two pivotal Phase III clinical trials were designated REFINE-1 and REFINE-2.

Outcomes: In both trials, at 12 weeks after the last treatment, 13% to 19% of patients who received Kybella had at least a two-grade improvement on both the Clinician-Reported Submental Fat Rating Scale and the Patient-Reported Submental Fat Rating Scale compared with 3% of patients who received placebo. At least 70% of patients who received Kybella had at least a one-grade improvement. The agency stated both efficacy measures were statistically significant. Kybella also led to statistically significant improvement on two secondary endpoints: magnetic resonance imaging scans of fat reduction and a patient-rated overall appearance scale.

Study Population and Protocol: The trials enrolled healthy adults (ages 19 to 65, BMI ≤ 40 kg/m²) with moderate or severe convexity or fullness associated with submental fat (grade 2 or 3 on 5-point grading scales), as judged by both clinician and subject ratings. Subjects received up to 6 treatments with Kybella (N=514, combined trials) or placebo (N=508, combined trials) at no less than 1 month intervals.

Dosing: Injection volume was 0.2 mL per injection site, spaced 1 cm apart into the submental fat tissue, also expressed as 2 mg/cm². In Phase 3 trials, doses of deoxycholic acid of 1 mg/cm² and 2 mg/cm² were evaluated. Subjects were treated with a maximum of four treatment sessions, spaced approximately 28 days apart, and follow-up was performed at 12 weeks. At each treatment session, patients were treated with a maximum of 50 injections. The maximum deoxycholic acid per injection was 0.2 mL, for a total maximum dose of 10 mL per treatment session.

Evidence Strength: Evidence for submental fat reduction is strong: two large, randomized, double-blind, placebo-controlled Phase III trials with a combined enrollment of over 1,000 adults, followed by regulatory approval. In April 2015, deoxycholic acid was approved by the FDA for the treatment of submental fat to improve aesthetic appearance and reduce facial fullness or convexity. It is marketed under the brand name Kybella by Kythera Biopharma and is the first pharmacological agent available for submental fat reduction, allowing for a safer and less invasive alternative than surgical procedures.

4.2 Lipoma Reduction (Off-Label Injection) — Preliminary Evidence

Sodium deoxycholate, mixed with phosphatidylcholine, is used in mesotherapy injections to produce lipolysis, and has been used as an alternative to surgical excision in the treatment of lipomas. Intralesional injections of deoxycholic acid are currently approved by the FDA for the removal of excessive submental fat, and the use of this compound for the treatment of lipomas is mainly off-label, with only a handful of cases documenting such use having been reported in the literature. One published case report documented the successful use of intralesional deoxycholic acid in a facial lipoma measuring 2.0 × 1.8 × 0.7 cm: the patient received—at intervals of 3 to 8 weeks—a total of 6 injections, reaching a total cumulative dose of 1 mL. During each treatment, 0.1 mL or 0.2 mL of a 10 mg/mL solution was evenly injected into the middle of the tumor using a 30-gauge needle. Follow-up evaluation at week 32 after treatment showed significant clinical improvement, with the lesion measuring 0.6 × 0.8 × 0.1 cm. Evidence for lipoma treatment is currently limited to case reports and small series, and cannot be considered clinically established.

4.3 Broader Localized Fat Reduction (Off-Label and Investigational)

A prospective study conducted in 2017 evaluated the efficacy and safety of a 1.25% sodium deoxycholate solution in 221 patients with various forms and degrees of localized fat. Injections were administered into the adipose tissue at 6-week intervals and continued until clinical results were achieved. Outcomes were assessed using before-and-after photographs and patient satisfaction questionnaires. Among 185 patients eligible for final evaluation, the mean treatment efficacy score reported by patients was 7.4, and medical assessment indicated treatment success in 93.5% of cases. Adverse events were mainly mild and localized at the injection site, with the incidence of severe complications being very rare. However, using Kybella for the treatment of fat outside of the submental area is not approved and is not recommended by the FDA.

4.4 Gastrointestinal and Carcinogenic Associations — Active Research Area

A substantial body of preclinical and epidemiological research has examined elevated DCA levels in relation to colorectal cancer risk. Deoxycholic acid (DCA), a microbial-derived secondary bile acid, plays a multifunctional role in gastrointestinal carcinogenesis through various molecular and cellular mechanisms. Mechanistically, DCA causes disruption of epithelial barrier function by occludin downregulation, claudin-5 disruption, and ERK signaling disruption, increasing permeability and inflammation. DCA triggers pro-oncogenic signaling such as β-catenin, M3 muscarinic receptor (M3R) transactivation of Epidermal Growth Factor Receptor (EGFR), and Nuclear factor kappa B (NF-κB), promoting cell proliferation, synthesis of Mucin 2 (MUC2), and pro-inflammatory cytokine release.

It has been reported that interplay between bile acids and gut microbiota could mediate the malignant transformation of colorectal adenomas, and the elevated levels of secondary bile acids, especially deoxycholic acid (DCA), play a critical role in this process. Gut bacterial metabolites, such as deoxycholic acid, contribute to the development of hepatocellular carcinoma and colon cancer by factors such as inflammation and oxidative DNA damage.

Deoxycholic acid (DCA) promotes inflammation and tumor progression by activating the NF-κB signaling pathway at low-to-moderate concentrations, whereas it induces apoptosis at high concentrations. Microbiota-mediated deconjugation, dehydroxylation, and epimerization of primary bile acids generate cytotoxic species such as deoxycholic acid (DCA) and lithocholic acid (LCA), which can trigger oxidative stress, lipid peroxidation, and DNA double-strand breaks (DSBs) via reactive oxygen species (ROS) accumulation.

Evidence Strength: The association between elevated DCA and gastrointestinal cancer risk is well-supported by in vitro experiments, animal studies, and epidemiological data, but causal inference in humans remains challenging. Most mechanistic data come from cell culture and rodent models. Clinical intervention data targeting the DCA-cancer axis in humans are limited.

4.5 Immune System Stimulation — Weak and Preliminary Evidence

Some publications point towards the effect of deoxycholic acid as an immunostimulant of the innate immune system, activating macrophages. According to these publications, a sufficient amount of deoxycholic acid in the human body would correspond with a good immune reaction of the non-specific immune system. Clinical studies conducted in the 1970s and 1980s are cited in support of this view, implicating DCA in natural healing processes of local inflammations, different types of herpes, and possibly cancer. This area of investigation is outdated in its study design and the claims cannot be considered substantiated by contemporary standards of clinical evidence. No modern controlled trials have validated DCA as an immunotherapeutic agent.

4.6 Corticosteroid Precursor — Historical Pharmaceutical Use (Discontinued)

Interest in DCA was revived in the 1940s when it was identified as a precursor for the synthesis of corticosteroids. Cortisone was a particularly promising new treatment against rheumatoid arthritis, and commercial production boomed after Sarett determined a process for synthesizing cortisone from DCA (1946). Since then, other precursors have been used for this application, but DCA still serves in several medical applications. This historical pharmaceutical role represents an industrial chemical use of DCA, not a direct therapeutic or supplementary use of the compound itself.

5. Body Systems and Health Areas Associated with Deoxycholic Acid

5.1 Gastrointestinal System

DCA is a principal actor in the digestive system, serving as a critical component of bile secreted into the small intestine to aid in the emulsification of dietary fats, increasing the surface area available for pancreatic lipases, and enhancing the digestion and absorption of fats and fat-soluble vitamins. Bile acids are perpetually recycled via enterohepatic circulation and are biotransformed by gut microbiota, making bile acid metabolism a critical regulator of intestinal homeostasis. Elevated DCA, however, is associated with increased intestinal permeability and pro-inflammatory signaling in the colonic mucosa.

5.2 Gut Microbiome

DCA is both a product of and a modulator of the gut microbiome. Changes in bile salt pool and composition due to changes in gut microbial composition contribute to the pathogenesis of inflammatory bowel disease and metabolic disease, possibly through altered activation of TGR5 and FXR. Dietary or genetic obesity has been shown to induce alterations in gut microbiota, thereby increasing the levels of DCA.

5.3 Hepatobiliary System

DCA participates in enterohepatic circulation, being absorbed in the distal ileum and returned to the liver. Deoxycholic acid is a secondary bile acid that increases the lithogenicity of bile. Water-soluble fiber found in fruits, vegetables, pectin, oat bran, and guar gum can bind this acid and may be helpful in preventing and treating gallstones. Elevated levels of hydrophobic bile acids including DCA can be hepatotoxic.

5.4 Adipose Tissue and Cosmetic/Aesthetic Medicine

When injected into subcutaneous fat, deoxycholic acid physically disrupts adipocyte cell membranes, leading to local adipocytolysis, cell death, and a mild, local inflammatory reaction consisting of macrophage infiltration and fibroblast recruitment. At Day 28 post-injection, inflammation largely resolves, and key histologic features include fibrotic septal thickening, neovascularization, and atrophy of fat lobules.

5.5 Immune and Inflammatory System

DCA plays an important role in many physiological processes including gut homeostasis, immune cell function, and inflammation. Synthetically derived deoxycholic acid, when injected, stimulates a targeted breakdown of adipose cells by disrupting the cell membrane and causing adipocytolysis. This results in an inflammatory reaction and clearing of the adipose tissue remnants by macrophages.

5.6 Oncology (Research Context)

The impact on host health is complex, as some secondary bile acids can be cytotoxic, contributing to oxidative stress, membrane damage, and colonic carcinogenesis, while others may exhibit anti-inflammatory and protective properties. The relationship between elevated colonic DCA concentrations and colorectal cancer risk is an active research area, with DCA currently viewed as a biologically plausible contributor to carcinogenesis in the context of high-fat diets and gut dysbiosis, rather than as a therapeutic agent in this domain.

6. Dosage Forms and Dosages Reported in Studies

As DCA is principally encountered in clinical/pharmaceutical contexts as a prescription injectable (not an oral supplement), dosage information refers specifically to studied pharmaceutical formulations:

• Approved injectable concentration: 10 mg/mL solution, supplied as a clear, colorless, sterile solution in 2 mL vials for single patient use. Each milliliter of the solution contains 10 mg of deoxycholic acid.
• Per-injection site dose: 0.2 mL per injection site, spaced 1 cm apart into the submental fat tissue, expressed as 2 mg/cm².
• Maximum per-session dose: At each treatment session, patients were treated with a maximum of 50 injections. The maximum deoxycholic acid per injection was 0.2 mL, for a total maximum dose of 10 mL per treatment session.
• Treatment interval and maximum sessions: Subjects received up to 6 treatments with Kybella or placebo at no less than 1 month intervals in the pivotal trials.
• Phase 3 dose levels studied: In Phase 3 trials, doses of deoxycholic acid 1 mg/cm² and 2 mg/cm² were evaluated.
• Off-label sodium deoxycholate (prospective study): A 1.25% sodium deoxycholate solution was evaluated in 221 patients with various forms and degrees of localized fat. Injections were administered into the adipose tissue at 6-week intervals and continued until clinical results were achieved.
• Lipoma case report dosing: A patient received a total of 6 injections at intervals of 3 to 8 weeks, reaching a total cumulative dose of 1 mL. During each treatment, 0.1 mL or 0.2 mL of a 10 mg/mL solution was evenly injected into the middle of the tumor using a 30-gauge needle.

Oral dosage forms of DCA as a dietary supplement are not well studied in controlled human trials, and no established oral supplemental dosage exists in the peer-reviewed literature reviewed here.

7. Safety Considerations and Interactions

7.1 Injection-Site Adverse Effects

Injection site reactions are very common (occurring in 96% of patients in clinical trials), and include edema/swelling (87%), hematoma/bruising (72%), pain (70%), numbness (66%), erythema (27%), induration (23%), paresthesia (14%), nodule (13%), and pruritus (12%). Bruising, itching, warmth, hardness, tingling or burning sensation, skin tightness, hair loss, open sores (ulcers), damage, and tissue cell-death (necrosis) around the injection site are other possible side effects.

7.2 Neurological Risk: Marginal Mandibular Nerve Injury

Marginal mandibular nerve injury, manifested as an asymmetric smile or facial muscle weakness (paresis), were reported during clinical trials. All marginal mandibular nerve injuries reported from trials resolved spontaneously. Temporary marginal mandibular nerve paresis has been reported in 2–4% of patients. Kybella can cause serious side effects, including nerve injury in the jaw that can cause an uneven smile or facial muscle weakness, and trouble swallowing.

7.3 Non-Selective Cytolysis Risk

Kybella is a cytolytic drug that destroys the cell membrane when injected into tissue. When properly injected into the fat tissue in the submental area, the drug destroys fat cells; however, it can also destroy other types of cells, such as skin cells, if it is inadvertently injected into the skin. The risk of non-selective tissue destruction is a fundamental pharmacological property of DCA and necessitates precise injection technique. A reported fatal case in the literature involved off-label cosmetic use: a case of a five-fold administration of a direct lipolytic phosphatidylcholine/deoxycholic acid formulation for cosmetic purposes resulted in widespread septal panniculitis, systemic inflammatory reaction, secondary myositis, thrombotic microangiopathic syndrome, fatty necrosis of the pancreatic head, necrotic nephrosis, and multiple organ failure, which led to the death of the patient.

7.4 Dysphagia

Difficulty swallowing (dysphagia) occurred in clinical trials in the setting of administration site reactions such as pain, swelling, and induration of the submental area; current or prior history of dysphagia may exacerbate the condition. Oropharyngeal pain, nausea, and dysphagia each occur in 1–10% of patients.

7.5 Drug Interactions: Anticoagulants and Antiplatelets

Patients using an antiplatelet medicine (e.g., aspirin) or a blood thinner (e.g., warfarin) should inform their prescribing physician, as these medicines may increase the risk of bleeding or bruising in the treatment area. Injection site hematoma/bruising was reported in 72% of patients treated; caution is warranted in patients with bleeding abnormalities or who are currently being treated with antiplatelet or anticoagulant therapy, as excessive bleeding or bruising in the treatment area may occur.

7.6 Contraindications

Kybella is contraindicated in the presence of infection at the injection sites. Caution should also be used in patients who have had prior surgical or aesthetic treatment of the submental area.

7.7 Special Populations

Although appropriate studies on the relationship of age to the effects of deoxycholic acid have not been performed in the geriatric population, no geriatric-specific problems have been documented to date. However, elderly patients are more likely to have age-related kidney, liver, or heart problems, which may require caution. There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. The clinical trials of Kybella did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.

7.8 Genotoxicity Testing

Long-term studies in animals have not been performed to evaluate the carcinogenic potential of Kybella injection. Kybella was negative in a battery of in vitro (Ames test and chromosomal aberration assay in human lymphocytes) and in vivo (rat erythrocyte micronucleus assay) genetic toxicology assays. It should be noted that the genotoxic potential described in the oncology literature (Section 4.4) refers to endogenous DCA at elevated colonic concentrations, a context distinct from the pharmacological injectable formulation.

7.9 Endogenous DCA and Gallstone Lithogenicity

In the context of endogenous physiology rather than injected pharmaceuticals, deoxycholic acid is a secondary bile acid that increases the lithogenicity of bile. Water-soluble fiber found in fruits, vegetables, pectin, oat bran, and guar gum can bind this acid and may be helpful in preventing and treating gallstones.

8. Research and Laboratory Applications

In research, deoxycholic acid is used as a mild detergent for the isolation of membrane-associated proteins. The critical micelle concentration for deoxycholic acid is approximately 2.4–4 mM. Sodium deoxycholate, the sodium salt of deoxycholic acid, is often used as a biological detergent to lyse cells and solubilise cellular and membrane components. Deoxycholates and bile acid derivatives in general are actively being studied as structures for incorporation in nanotechnology. They have also found application in microlithography as photoresistant components. Unconjugated bile salts including deoxycholic acid at their minimum inhibitory concentration have been shown to kill S. aureus, associated with increased membrane disruption and leakage of cellular contents, though this antimicrobial property has not been developed into a clinical treatment.

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