Cetyl Myristate and Cetyl Myristoleate: A Comprehensive Reference Article
Nomenclature, Identity, and Scope
The terms cetyl myristate and cetyl myristoleate refer to two closely related but chemically distinct fatty acid esters belonging to the family of cetylated fatty acids (CFAs). Both compounds are prominent components of commercial supplement preparations, and they are frequently discussed together in the scientific literature. This article covers both compounds, with emphasis on cetyl myristoleate (CMO), the member with the most documented research history, and addresses cetyl myristate as it appears in formulations and regulatory assessments.
Cetyl myristoleate (CMO) is a fatty acid ester, or more specifically, a cetylated fatty acid (CFA); it is the cetyl ester of myristoleic acid. It is more formally known as cis-9-cetyl myristoleate. It is chemically designated as hexadecyl (Z)-tetradec-9-enoate, with the molecular formula C₃₀H₅₈O₂. Myristoleic acid is technically known as 9-cis-tetradecenoic acid, a 14-carbon monounsaturated omega-5 fatty acid.
Cetyl myristate is the saturated analogue: the cetyl ester of myristic acid, carrying the molecular formula C₃₀H₆₀O₂ (PubChem CID 75779). Cetylated fatty acids are fatty acids esterified with the long-chain (C16) aliphatic, saturated, primary alcohol cetyl alcohol (1-hexadecanol, palmityl alcohol); the oil's major components in commercial preparations are the esters cetyl (palmityl) myristate and cetyl (palmityl) myristoleate, each about 40% of the oil.
In the case of CMO, the alcohol component is cetyl alcohol and the acid is myristoleic acid. CMO belongs to a chemical group of cetylated fatty acids, which also includes cetyl myristate, cetyl laurate, cetyl oleate, cetyl palmitate, and cetyl palmitoleate.
Natural Sources
Cetylated fatty acids are a group of naturally occurring fats of plant and/or animal origin. Cetyl myristoleate is found in certain animals, including cows, whales, beavers, and mice. Myristoleic acid has undetermined biological significance in humans. It is a natural component of the fat of whales, beavers, and bovines, and its cetylated form, cetyl myristoleate, is found in a particular species of laboratory mouse.
Natural cetylated fatty acids are rare. Dietary foods such as fish oils, beef tallow, and full-fat dairy contain only trace amounts. Commercially, Cetyl Myristoleate Complex (CMC) powder consists of 50% of cetylated fatty acids (CFA, including 20% of cetyl myristoleate), 48% of corn starch, and 2% of silicon dioxide; CMC is produced in an industrial process where a fatty acid mixture extracted from beef tallow is esterified with cetyl alcohol obtained from palm oil.
Until 1999, all commercial cetyl myristoleate was based on a mixture of bovine straight-chain fatty acids containing mainly two 14-carbon, straight-chain fatty acids, myristic and myristoleic. The commercial source was beef tallow, a by-product of the beef rendering industry. The beef tallow (a triglyceride) is split to produce free fatty acids and glycerine, which are then fractionated by distillation, yielding a high myristoleic acid-containing stream; esterification of these fatty acids with cetyl alcohol forms cetyl myristoleate and cetyl myristate.
An alternative, plant-derived source also exists. Celadrin is a patented combination of cetylated, esterified fatty acids containing cetyl myristoleate, cetyl myristate, cetyl palmitoleate, cetyl laurate, cetyl palmitate, and cetyl oleate extracted from plant-based sources, with oils including palm, palm kernel, olive, nutmeg, coconut, and unsaturated vegetable oils.
Common Forms and Preparations
As a nutritional supplement, cetyl myristoleate is found in a highly purified, refined form in capsules and tablets. CMO is also available in creams and lotions for topical application. A more recent novel food application concerns primarily a mixture of cetylated myristic acid and cetylated oleic acid synthesised from cetyl alcohol, myristic acid, and oleic acid, and to a lesser degree, other cetylated fatty acids and other compounds from olive oil. This novel food is a mixture of cetyl myristate and cetyl oleate blended with olive oil to give a finished product containing 70–80% cetylated fatty acids.
As CMO is not an essential nutrient, no deficiency state exists.
Historical Discovery and Background
Cetyl myristoleate was isolated for the first time by Dr. Harry Diehl at the Laboratory of Chemistry of the National Institute of Arthritis, Metabolic, and Digestive Diseases in Bethesda, Maryland. Dr. Diehl had tried to unsuccessfully induce polyarthritis in Swiss albino mice using Freund's adjuvant (heat-killed desiccated Mycobacterium butyricum) but realized that they were immune.
Further investigation revealed that cetyl myristoleate was what was causing the mice to be immune to becoming arthritic. The compound was isolated and identified using thin layer chromatography.
Cetyl myristoleate (CM), as an arthritis palliative, was discovered by Harry Diehl in 1964. Diehl's work led to the issuance of two U.S. patents on cetyl myristoleate — one in 1977 and a second in 1996. His findings were published in the Journal of Pharmaceutical Sciences in March 1994, a peer-reviewed publication of the American Pharmaceutical Association and the American Chemical Society.
Cetyl myristoleate has been prepared by an esterification reaction between myristoleic acid and cetyl alcohol, catalyzed by p-toluenesulfonic acid monohydrate.
There is no documented traditional use of cetyl myristoleate in any pre-modern cultural or herbal medical tradition. The compound was unknown before its isolation in modern laboratory conditions, and its entire history as a health-relevant substance is scientific rather than ethnobotanical. It is rated in evidence databases as receiving minimal or no scientific evidence support for traditional use; for a supplement, there is little scientific support.
Chemical Identity of Key Constituents
Commercial preparations typically contain a mixture of CFAs rather than isolated cetyl myristoleate alone. The key constituents include:
- Cetyl myristoleate (CMO): A naturally occurring wax ester and fatty acid derivative, chemically designated as hexadecyl (Z)-tetradec-9-enoate, molecular formula C₃₀H₅₈O₂.
- Cetyl myristate: The fully saturated analogue, molecular formula C₃₀H₆₀O₂ (PubChem CID 75779), differing from CMO by the absence of the double bond.
- Other cetylated fatty acids: CMO belongs to a chemical group that also includes cetyl laurate, cetyl oleate, cetyl palmitate, and cetyl palmitoleate.
In animal studies, related esters like cetyl oleate offered only partial protection against arthritis, while cetyl myristate and cetyl elaidate were ineffective, highlighting cetyl myristoleate's specific activity.
Proposed Mechanisms of Action
The precise mechanisms by which cetyl myristoleate exerts its biological effects remain incompletely characterized. Multiple hypotheses have been advanced in the scientific literature:
Immune Modulation
It is believed to act on memory T-cells in the immune system — it may "re-program" them so they do not attack one's own connective tissues. This proposed mechanism is the basis for interest in CMO for autoimmune and inflammatory joint conditions, though direct mechanistic human evidence remains limited.
Cell Membrane Effects / Anti-inflammatory Activity
This dietary supplement is believed to work in a similar way to the essential fatty acids from fish oil, enhancing cell membrane integrity and reducing inflammation. Cetylated fatty acids might help lubricate joints and muscles, soften tissues, and increase flexibility; they also might help the immune system and reduce swelling.
Prostaglandin and Leukotriene Modulation
Cetylated fatty acids have been reported to reduce pain by decreasing the production of key mediators. Among the proposed mechanisms in the supplement literature is regulation of prostaglandin and leukotriene production, which are key inflammatory signaling molecules. However, these mechanistic claims derive primarily from in vitro and preclinical data.
In Vitro Chondrogenesis Data
One study investigated the possible mechanisms of Celadrin cetylated fatty acids action at the cellular level on inflammation-related pain relief and chondrogenesis, testing the effects of the cetylated fatty acids mixture on an in vitro scaffold-free three-dimensional mesenchymal stem cells culture model of chondrogenesis. Several clinical studies have shown that Celadrin is supportive of the lubrication of affected joints and reduces the production of IL-6.
ADME Considerations
A key unresolved question regarding mechanism involves whether CFAs are hydrolyzed in the gut before absorption or absorbed intact. From available information on absorption and distribution after oral and topical administration in rats, it appears that a small amount of CFA is absorbed intact. No information was provided on the extent of intestinal hydrolysis of the CFA after oral intake, limited information exists on the distribution of absorbed unhydrolyzed CFA, and no information was provided on the metabolism and excretion of intact CFA. An in vitro hydrolysis study demonstrated a low rate of hydrolysis of cetyl myristoleate and cetyl myristate, and regulators noted that this raised the need for adequate safety information on the unhydrolyzed esters.
Scientific Evidence by Health Area
Animal (Preclinical) Studies
In animal studies, cetyl myristoleate was first reported to block inflammation and prevent adjuvant-induced arthritis at very high doses in rats.
To validate the theory that cetyl myristoleate could prevent arthritis in rodents, Diehl injected two groups of rats with the arthritis-inducing Freund's adjuvant. After 20 days, both groups had no visible sign of arthritis. Then, a group was re-injected with the adjuvant while the other group received an injection of cetyl myristoleate followed by an injection of the adjuvant 48 hours later. After 58 days of observation, the rats that had not received cetyl myristoleate injections had developed swelling, had grown on average 5.17 times less than the other group, and were lethargic. The rats who received cetyl myristoleate injections were healthy and growing at a normal rate.
Subcutaneous administration of CM at doses of 450–500 mg/kg provided virtually complete protection against arthritis development, blocking inflammation and preventing joint involvement when given prophylactically prior to adjuvant injection.
These animal findings were foundational for subsequent human research but were conducted at very high parenteral doses. Translating these findings to oral human supplementation involves significant uncertainties in dose scaling and route of administration.
Osteoarthritis: Human Clinical Evidence
The most studied area for cetyl myristoleate and CFAs in humans is osteoarthritis (OA), particularly of the knee. The overall weight of human evidence is rated as limited by independent systematic reviewers. Limited evidence was found for cetyl myristoleate in osteoarthritis, alongside lipids from green-lipped mussels, and plant extracts from Harpagophytum procumbens.
Siemandi 1997 Trial: In 1997, a prospective randomized study conducted by H. Siemandi showed that after 32 weeks of observation, cetyl myristoleate had clearly superior efficacy in terms of reducing the frequency of arthritic episodes when compared to control groups of patients who received a mixture of natural compounds or a placebo. Siemandi conducted a multicenter, double-blind, placebo-controlled clinical trial involving 382 patients with osteoarthritis, rheumatoid arthritis, and psoriatic arthritis. One group used 90g/day CM complex containing 12% CM; a second group took the same amount of CM complex plus glucosamine hydrochloride, sea cucumber, and hydrolyzed cartilage; and the third group took a placebo. Outcome was measured by patient response, physician assessment, joint pain, swelling scores, and several measures of range of motion. According to one source, results showed 63% improvement for the cetyl myristoleate group, 87% for the cetyl myristoleate plus glucosamine group, and 15% for the placebo group. However, this trial has not been published in a major peer-reviewed journal and its full methodology has not been independently reproduced.
Hesslink et al. 2002 (Journal of Rheumatology): The Hesslink 2002 study examined patients with knee OA (mean age 56.8 years) in a single-blind parallel study (n = 66) over 68 days. The cetyl myristoleate arm received 350 mg cetyl myristoleate, 50 mg soy lecithin, and 75 mg fish oil; the placebo group received soy lecithin 500 mg. Knee flexion improved +10.1 degrees in the cetyl myristoleate group versus +1.1 degrees in the placebo group (p < 0.001). The study was single-blind, limiting the strength of its conclusions. Taking a specific blend of cetylated fatty acids (Celadrin) combined with soy lecithin and fish oil by mouth seems to decrease pain and improve knee range of motion and function in people with knee osteoarthritis.
Kraemer et al. 2004 (Journal of Rheumatology) — Topical: Kraemer WJ, Ratamess NA, Anderson JM et al. published a study on the effect of a cetylated fatty acid topical cream on functional mobility and quality of life of patients with osteoarthritis, published in the Journal of Rheumatology 2004;31:767–74.
Kraemer et al. 2005 (Journal of Strength and Conditioning Research) — Topical with Menthol: Kraemer WJ, Ratamess NA, Maresh CM et al. published findings that a cetylated fatty acid topical cream with menthol reduces pain and improves functional performance in individuals with arthritis, in the Journal of Strength and Conditioning Research 2005;19:475–80.
Ariani et al. 2018 (Archives of Rheumatology) — Topical, Multi-center: Ariani A, Parisi S, Guidelli GM et al. reported a short-term effect of topical cetylated fatty acid on early and advanced knee osteoarthritis in a multi-center study, published in Archives of Rheumatology 2018;33(4):438–442.
Mohebi et al. 2023 (Mediterranean Journal of Rheumatology) — Oral vs. Meloxicam: This study aimed to assess how effective an oral form of CFA is in improving physical function, pain, and stiffness in individuals suffering from knee OA compared to meloxicam (an NSAID). For this parallel-arm randomised clinical trial, 48 adult patients with knee OA were divided into two groups; the intervention group was prescribed 350 mg CFA capsule three times per day for 30 days, while the control group was given 15 mg of Meloxicam, one tablet daily for ten days. Patients completed the Oxford Knee Score, WOMAC, and Visual Analog Scale. Data were obtained at baseline and two, four, and eight weeks after the final dose of each intervention. Studies on oral forms of CFA in the treatment of OA have been relatively lacking.
Zodeleva et al. 2025 — Randomized Double-Blind Placebo-Controlled: A 2025 publication from the European Journal of Clinical Nutrition assessed the efficacy and safety of a CFA-based dietary supplement in patients with knee OA, described as a prevalent and difficult-to-treat condition. This represents one of the more rigorously designed trials but had not yet been fully indexed at the time of review.
Systematic Evidence Rating: Although cetyl myristoleate is sold as a dietary supplement, its possible benefits in the treatment of any medical condition are not completely established, and the Federal Trade Commission has taken legal action against supplement manufacturers for inaccurate claims. There is some clinical evidence for the benefits of CFAs, which may contain cetyl myristoleate, in arthritic patients. One pilot study found that cetyl myristoleate may be beneficial against fibromyalgia, and there have been other studies. However, these low-quality clinical trials provide only limited scientific evidence of efficacy.
Musculoskeletal Pain: Other Areas
CFAs have shown to reduce pain by decreasing the production of key mediators and have been studied in conditions including athletic pubalgia, shoulder tendinopathies, and osteoarthritis. One study aimed to investigate whether short-term supplementation of oral CFAs reduces pain and disability in patients with axial discogenic low back pain. The study included 27 patients with an average age of 57 ± 16 years diagnosed with axial discogenic low back pain, with primary outcome the Oswestry Disability Index (ODI) score and secondary outcomes including Numeric Pain Rating Scale scores and adverse events.
A real-world observational study evaluated decrease in pain after 30-day administration of a new oral CFA food supplement, assessed whether decreased pain resulted in lower consumption of oral NSAIDs, and evaluated improvement in related gastric side effects. It was described as the first study of this food supplement in a real-world setting; 120 Italian primary care physicians recruited 562 patients who were prescribed oral CFA, and patients completed the Brief Pain Inventory questionnaire at baseline and after 30 days.
Fibromyalgia
Preclinical and clinical data show potential benefits in the management of arthritis and fibromyalgia. Health conditions that have been hypothesized to benefit from cetylated fatty acid supplementation include fibromyalgia, among others. Far more scientific study is necessary to support these many claims.
Autoimmune and Rheumatic Conditions
Cetylated fatty acids are also used for other types of arthritis including rheumatoid arthritis (RA), osteoarthritis (OA), Reiter's syndrome, and ankylosing spondylitis. They are also used for diseases in which the body attacks itself (autoimmune diseases) including Sjögren's syndrome, systemic lupus erythematosus (SLE), and multiple sclerosis (MS). However, there is not enough scientific data to conclude on the effectiveness of cetylated fatty acids in the treatment of rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, Behçet's disease, Reiter's syndrome, psoriasis, fibromyalgia, emphysema, benign prostatic hyperplasia, leukemia and other cancers, as well as various types of back pain. Further scientific research is needed to evaluate the effectiveness of cetylated fatty acids in these applications.
Body Systems and Health Areas of Association
- Musculoskeletal system: The primary area of research and use. Proposed roles in joint lubrication, cartilage support, and reduction of articular inflammation. Most clinical evidence pertains to knee OA.
- Immune system: Cetylated fatty acids might help lubricate joints and muscles, soften tissues, and increase flexibility; they also might help the immune system and reduce swelling.
- Inflammatory pathways: CFAs have been reported to reduce pain by decreasing the production of key inflammatory mediators.
- Cell membranes: This dietary supplement is believed to work in a similar way to the essential fatty acids from fish oil, enhancing cell membrane integrity and reducing inflammation.
Dosage Forms and Reported Dosages
Dosages reported across the scientific and clinical literature vary considerably. There is currently no established consensus therapeutic dose.
- Generally, CMO is taken in the amount of 400 to 500 mg daily for 30 days (as cited in one general clinical reference).
- In the Hesslink 2002 trial, the cetyl myristoleate arm received 350 mg CMO, 50 mg soy lecithin, and 75 mg fish oil over 68 days.
- In the Mohebi 2023 trial, the intervention group was prescribed a 350 mg CFA capsule three times per day (i.e., 1,050 mg/day) for 30 days.
- Dosages for oral use typically range from 1,000 to 2,000 milligrams daily when taken orally, or through topical application of creams multiple times a day (as cited in EBSCO Research Starters).
- One commercial applicant suggested a daily dose of 3.3 g CMC corresponding to approximately 660 mg of cetyl myristoleate and cetyl myristate combined.
- There is currently no consensus on a standardised therapeutic dosage or optimal treatment duration for CFAs.
Safety Considerations
EFSA Regulatory History
The European Food Safety Authority (EFSA) has reviewed the safety of Cetyl Myristoleate Complex (CMC) on multiple occasions, making a series of progressively updated findings.
Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies was asked to update its opinion on the safety of 'Cetyl Myristoleate Complex' (CMC) as a novel food ingredient. In its 2010 opinion, the Panel concluded that based on the available data, the safety of CMC as an ingredient in food supplements had not been established.
The Panel's 2010 conclusion was based on the consideration that in the absence of appropriate data on absorption, distribution, metabolism, and excretion, the provided toxicological data were insufficient.
EFSA reiterated its previous conclusion from 2010 that the safety of 'Cetyl Myristoleate Complex' has not been established. The conclusion of the 2010 EFSA Opinion was that the safety of Cetyl Myristoleate Complex had not been established; in 2012, the Commission requested EFSA to review this Opinion based on new information, and on 31 May 2013, EFSA adopted a statement reiterating its view that the safety of the product could not be established.
In 2021, a new application under the EU Novel Food Regulation led to a more favorable conclusion for a different formulation. The highest dose tested in a subchronic toxicity study in rats — 4,500 mg/kg per day — was considered to be the no-observed-adverse-effect level. By applying the default uncertainty factor of 200 and considering a default body weight of 70 kg for the adult target population, this results in an intake of 1.6 g per day. The Panel concluded that the novel food, cetylated fatty acids, is safe at an intake of 1.6 g per day for the intended target population.
They concluded that CFAs are safe for the adult population at an intake of 1,600 mg per day, without major complications such as genotoxicity or subacute/chronic toxicity.
Gastrointestinal Effects
Cetyl myristoleate, often formulated as part of cetylated fatty acids or CMC, has demonstrated a generally favorable safety profile in available studies, with no serious adverse events reported in short-term human use up to 3 months. In a randomized controlled trial of 30 patients with knee osteoarthritis receiving cetylated fatty acids orally for 60 days, only 4 participants reported mild adverse events, primarily gastrointestinal discomfort such as nausea or upset stomach, with no dropouts due to safety concerns.
Topical Safety
When applied to the skin, cetylated fatty acids are possibly safe when used for up to 30 days. Some people might be sensitive to creams containing cetylated fatty acids, but they are usually well-tolerated.
Long-term Safety and Data Gaps
There is not much information on the safety of long-term use. Considering the absence of appropriate data on kinetics of hydrolysis, adequate safety information on the parent compound (i.e., CFAs), which potentially may not be hydrolyzed in the human gut and may be absorbed intact as an ester, remains relevant.
Interactions
At the time of writing, there were no well-known supplement or food interactions with this supplement. There are no known drug interactions with cetyl myristoleate based on available veterinary reference data. There is insufficient reliable information to know what an appropriate dose of cetylated fatty acids might be.
Regulatory / FTC Action
Although cetyl myristoleate is sold as a dietary supplement, its possible benefits in the treatment of any medical condition are not completely established, and the Federal Trade Commission has taken legal action against supplement manufacturers for inaccurate claims.
Summary of Evidence Strength
The overall body of evidence for cetyl myristoleate and cetylated fatty acids is characterized by a small number of human trials, most of which are of limited methodological quality (small sample sizes, single-blind designs, short durations, and use of multi-ingredient formulations that make it difficult to attribute effects to cetyl myristoleate specifically). Research indicates that cetylated fatty acids may have limited effectiveness for treating related conditions such as knee and shoulder pain, and there are ongoing discussions about their potential benefits for psoriasis and various autoimmune diseases. While some proponents claim that cetylated fatty acids can reduce inflammation and protect joint health, the scientific support for these claims remains sparse. Independent systematic reviewers classify the available evidence as "limited" for osteoarthritis specifically, and as "insufficient" for all other conditions currently claimed.
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