Myristic acid

Myristic Acid (Tetradecanoic Acid)

1. Identity and Chemical Characterization

Myristic acid (IUPAC name: tetradecanoic acid) is a common saturated fatty acid with the molecular formula CH₃(CH₂)₁₂COOH. It was discovered by Playfair L. in 1841 in the nutmeg, the seed of the tropical tree Myristica fragrans, from which its name is derived. According to the LIPID MAPS Structure Database, it belongs to the category of Fatty Acyls, class Fatty Acids and Conjugates, and sub-class of straight-chain fatty acids.

Myristic acid is defined as a 14-carbon, straight-chain saturated fatty acid found in various fats throughout the plant and animal kingdom, commonly present in human foodstuffs. It belongs to the group of saturated fatty acids, with no double bond, so its shorthand notation is 14:0. It is also a member of the group called long-chain fatty acids (LCFA), covering 14 to 18 carbon atoms.

Synonyms and Identifiers

• Common synonyms include C14:0, FA 14:0, NSC 5028, and Tetradecanoic Acid.
• Molecular weight: 228.37 g/mol; molecular formula: C₁₄H₂₈O₂; CAS registry number: 544-63-8.
• Its salts and esters are commonly referred to as myristates or tetradecanoates.
• The name of the acyl group derived from myristic acid is myristoyl or tetradecanoyl.

Physical and Chemical Properties

At room temperature, myristic acid appears as white or yellowish glossy crystals with a faint, waxy-oily odor. In purified form it is a white solid insoluble in water, with a melting point at 53.9 °C (129.02 °F; 327.05 K) and a boiling point at 250 °C (482 °F; 523.15 K) at 100 mmHg. It is not soluble in water but soluble in ethanol, ether, and chloroform.

Common Forms and Preparations

To prepare myristic acid industrially, the methyl ester of mixed fatty acids obtained from coconut oil or palm kernel oil is subject to vacuum fractionation. It is used as an ingredient in soaps and shaving creams, often in the form of the ester isopropyl myristate. Isopropyl myristate is a polar emollient and is used in cosmetic and topical pharmaceutical preparations as a penetration enhancer where skin absorption is desired. Myristic acid is used in oral and topical pharmaceutical formulations. It has been evaluated as a penetration enhancer in melatonin transdermal patches in rats and bupropion formulations on human cadaver skin, and further studies have assessed its suitability in oxymorphone formulations and clobetasol 17-propionate topical applications.

2. Natural Sources

Plant Sources

Nutmeg butter is 75% trimyristin, the triglyceride of myristic acid — myristic acid predominates in the fats of the Myristicaceae family. Among vegetable fats and oils, a particularly rich plant source is coconut oil, with about 17 g per 100 g of edible portion. In fruit, it is present in high amounts only in dried and fresh coconut, like lauric acid, at 9.5 and 5.4 g per 100 g of edible portion, respectively. Among other vegetable oils, only palm oil has concentrations that reach 1 g per 100 g of edible portion, whereas it does not exceed 0.86 g per 100 g of edible portion in margarine, and it is absent in peanut butter. It is present in small amounts in a few cereals (maize, at 0.28 g per 100 g of edible portion, is the richest cereal source), and it is absent in legumes.

Animal Sources

Dairy fat, such as butter and cow's milk, is a significant source, often containing between 8% and 14% myristic acid. Myristic acid is one of the most abundant fatty acids in milk fat, comprising above 10% of total fatty acids. It also makes up a small percentage of human milk and is even found in spermaceti, the oil historically extracted from sperm whales.

Industrial Production and Consumption

The primary dietary sources for industrial production of purified myristic acid are coconut oil and palm kernel oil, where it is present alongside lauric acid; these two oils are the main starting materials for industrial-scale manufacturing. Annual consumption of myristic acid naturally present in food has been reported at approximately 10,798,307 kg, while consumption as an added flavor is only approximately 640 kg per year, suggesting that the vast majority of consumption is from natural food sources.

3. Traditional and Historical Use

Nutmeg (Myristica fragrans) is an important ethnomedicinal resource with both dietary and therapeutic significance in traditional Asian medical systems. Its use dates back to its introduction into China around the 3rd–4th centuries CE, with classical medical texts documenting its core functions of "warming the middle jiao to promote qi flow, and astringing the intestines to relieve diarrhea."

Myristica fragrans Houtt, commonly known as nutmeg, is described in nearly every traditional medicine system: Ayurveda, Siddha, Unani, and folk systems. It has a wide range of fixed oils and essential oils, among them myristic acid, trimyristicin, myristicin, safrole, eugenol, elimicin, and meso-dihydroguaiaretic acid.

In the Ayurvedic tradition, nutmeg — the most concentrated natural source of trimyristin (the triglyceride form of myristic acid) — was described under the Sanskrit name Jatiphala (also Jaiphal). Ayurvedic preparations incorporating nutmeg included Jatiphaladi Churna (used in digestive and respiratory conditions), Dadimavaleha (used to relieve diarrhea and dysentery), and Nasika Churna (used in the treatment of chronic rhinitis, headache, and bad breath). These preparations delivered myristic acid and its associated phytochemicals as part of a complex whole-plant matrix.

The Myristicaceae family is the source of two spices — nutmeg (Jaiphal) and mace (Javitri) — used around the world, described in nearly every medicine system including Ayurveda, Siddha, Unani, and folk traditions.

Important distinction: The traditional uses documented above refer to preparations of Myristica fragrans (nutmeg) and its fixed oils as a whole. Myristic acid as an isolated compound was not available before the 19th century and was not itself the basis of traditional therapeutic use. The therapeutic actions attributed to nutmeg in these traditions were assigned to the plant as a whole, and multiple phytochemicals — not myristic acid alone — are regarded by contemporary researchers as contributors to its pharmacological effects.

4. Key Constituents and Mechanisms of Action

4.1 The Fatty Acid Itself: Structure and Biochemical Role

N-myristoylation is the attachment of myristic acid, a 14-carbon fatty acid (myristate), onto the N-terminal glycine residue of target proteins, catalysed by N-myristoyltransferase (NMT), a ubiquitous and essential enzyme in eukaryotes. Many of the target proteins of NMT are crucial components of signalling pathways, and myristoylation typically promotes membrane binding that is essential for proper protein localisation or biological function.

N-myristoylation is a ubiquitous protein lipid modification that occurs cotranslationally in eukaryotes and involves attachment of myristic acid to the N-terminal glycine (Gly) of a wide range of substrate proteins. Although N-myristoylation generally occurs cotranslationally on newly synthesised polypeptides following the removal of the initiator methionine by methionine aminopeptidase (MetAP2), there is also evidence of posttranslational myristoylation on an internal Gly exposed by caspase cleavage during apoptosis.

4.2 The Myristoyl Switch and Cell Signalling

Myristoylation is a protein lipid modification that plays vital roles in cellular signalling, protein–protein interaction, and targeting of proteins to endomembrane and plasma membrane systems. The attachment of myristic acid to the N-terminus is catalysed by the ubiquitous eukaryotic enzyme N-myristoyltransferase (NMT), a prosurvival protein which uses myristoyl-coenzyme A (CoA) as a substrate.

N-myristoylation is the addition of the 14-carbon fatty acid myristate to proteins. This plays a fundamental role in cell signalling: over 500 proteins are myristoylated, including all 9 Src Family Kinases (Src, Lyn, Lck, Hck, and Fgr), as well as c-Abl, Gα subunits, caspase-truncated (ct-)Bid and ct-PAK2, regulating cell growth and apoptosis. Human myristoylation is performed by two ubiquitously expressed N-myristoyltransferases, NMT1 and NMT2.

Myristate originates through de novo biosynthesis (e.g., in plants), from external uptake (e.g., in human tissues), or from mixed origins (e.g., in unicellular organisms). Myristate usually serves as a molecular anchor, allowing tagged proteins to be targeted to membranes and to travel across endomembrane networks in eukaryotes.

4.3 N-myristoylation in Viral and Immune Biology

Myristoylation-dependent regulation plays a key role in HIV biology. The principal targets of HIV are mostly cells that express CD4 and CCR5 or CXCR4 surface receptors. Upon entering its target cells, HIV integrates inside its host genome. Subsequently, there is production of both host and viral proteins that drive the progression of HIV to AIDS. For example, the viral protein Nef is cotranslationally modified by the host's NMT, which ensures its interaction with and downregulation of the host cell surface receptors (CD4 and MHC1). NMT also mediates the assembly and multimerisation of Gag at the plasma membrane during budding and viral release events.

4.4 Effects on Membrane Lipids and Ceramide Synthesis

Myristic acid, a free fatty acid highly abundant in copra/palmist oils, is described as a predictor of nonalcoholic steatohepatitis (NASH) and stimulates ceramide synthesis. Research has investigated the synergism between myristic acid and palmitic acid in ceramide synthesis, ER stress, lipotoxicity, and NASH. Unlike palmitic acid, myristic acid is not itself lipotoxic but potentiated palmitic acid-mediated lipoapoptosis, ER stress, caspase-3 activation, and cytochrome c release in primary mouse hepatocytes. Moreover, myristic acid kinetically sustained palmitic acid-induced total ceramide content by stimulating dehydroceramide desaturase. These findings are preclinical (cell-culture based) and require further confirmation in human models.

5. Scientific Evidence by Area

5.1 Cardiovascular Health: Plasma Lipids and Lipoproteins

Overview: The relationship between myristic acid and cardiovascular risk markers has been studied principally through controlled dietary intervention trials comparing fat substitutions, epidemiological serum biomarker analyses, and meta-analyses of saturated fatty acid intake.

LDL-raising effect: Dietary myristic acid has been shown to raise total cholesterol concentrations. Serum myristic acid, measured as molecular percentages, was shown to predict serum total cholesterol concentrations in a manner consistent with its dietary cholesterol-raising effects. In a cross-sectional analysis of a population-based survey of New Zealand adults (n = 2,732), the molecular percentage of serum myristic acid — a marker of dietary saturated and dairy fat — was positively associated with total cholesterol.

HDL effects and complexity: A clinical study in young men concluded that the intake of individual dietary saturated fatty acids may affect fasting HDL cholesterol within 24 hours, with HDL cholesterol concentration higher after myristic acid compared to stearic acid. A change in the proportions of ingested fatty acids that affects the ratio of HDL cholesterol to LDL cholesterol may be more important than simply limiting saturated fats, with both myristic and stearic acids influencing HDL cholesterol levels.

Moderate dairy fat intake studies (Dabadie et al.): A clinical interventional study compared the effects of two moderate intakes of myristic acid on plasma lipids. Twenty-five male monks without dyslipidaemia were given two isocaloric diets for 5 weeks each; in diet 1, 30% of calories came from fat (8% SFA, 0.6% myristic acid) providing 200 mg cholesterol per day. Study participants were between 35 and 88 years of age (average 61 years) with a BMI averaging 25 kg/m², and none had a history of atherosclerotic disease. A moderate intake of myristic acid from dairy products, located mainly at the sn-2 position of triglycerides, was shown to enhance long-chain omega-3 fatty acid levels (20:5 n-3 and 22:6 n-3) in plasma phospholipids. Further research indicated that myristic acid from dairy fat exerted a beneficial effect on lipid biomarkers by increasing HDL cholesterol and decreasing TAG levels, without changes in LDL cholesterol.

A further 1-year nutritional study evaluated the effects of moderate intakes of myristic acid at 1.2% and 1.8% of total energy, associated with a 0.9% total energy intake of α-linolenic acid, on lipid and fatty acid profiles and red blood cell membrane fluidity. Twenty-nine monks without dyslipidaemia were enrolled, and two experimental diets were tested for 3 months each.

CHD risk biomarker studies: Of three studies investigating circulating levels of myristic acid in relation to coronary heart disease (CHD) risk, none found evidence for an association in either direction (Khaw et al., 2012; Simon et al., 1995; Wu et al., 2011). Food sources of myristic acid include nutmeg, palm kernel, and butter, though the total contribution to dietary saturated fatty acid intake is low, reflected in the relatively small proportion in circulating fatty acids (<1%).

Evidence strength assessment: The lipid-altering effects of myristic acid at the population level are based on a combination of controlled feeding trials (generally small and short-term), cross-sectional biomarker studies, and extrapolations from broader saturated fat research. Clinical trials offer conflicting conclusions regarding the role of saturated fatty acids and the risk of ischaemic heart disease. A growing number of studies indicate that the impact of saturated fat on CVD mortality is not so much dependent on the overall amount of saturated fat but rather on its ratio to unsaturated fatty acids. A Cochrane meta-analysis showed moderate-quality evidence that replacing saturated fat with polyunsaturated fat reduces the risk of CVD events and myocardial infarction, but no effect was found for all-cause or IHD-specific mortality. Overall, the clinical evidence regarding myristic acid specifically (as opposed to saturated fat in general) is limited, mixed, and largely based on dietary substitution studies rather than isolated supplementation.

5.2 N-myristoylation: Cellular Protein Regulation

Protein N-myristoylation is a cotranslational lipidic modification specific to the alpha-amino group of an N-terminal glycine residue of many eukaryotic and viral proteins, catalysed by the ubiquitous eukaryotic enzyme N-myristoyltransferase. Attachment of a myristoyl group increases specific protein–protein interactions leading to subcellular localisation of myristoylated proteins with their signalling partners. Research over roughly three decades has led to understanding of the significance of protein myristoylation in regulating cellular signalling pathways in carcinogenesis and more recently in immune function.

This mechanistic body of knowledge is based predominantly on biochemical, cellular, and molecular biology research (in vitro and in vivo animal models). There are no clinical dietary trials directly assessing whether supplemental myristic acid alters N-myristoylation outcomes at physiologically relevant doses in healthy humans. The pharmaceutical relevance of this pathway lies primarily in NMT enzyme inhibition (not myristic acid supplementation) for therapeutic purposes.

5.3 NMT as a Drug Target: Cancer and Infectious Disease

NMT is a validated therapeutic target in opportunistic infections of humans by fungi or parasitic protozoa. Additionally, NMT is implicated in carcinogenesis, particularly colon cancer, where there is evidence for its upregulation in the early stages of tumour formation. Human N-myristoyltransferase has attracted increasing interest as a target in cancer and infectious diseases.

It is important to emphasise that this area of research concerns the therapeutic blocking of the NMT enzyme (using small-molecule inhibitors), rather than the dietary or supplemental use of myristic acid itself. The clinical relevance of myristic acid as an exogenous supplemented substrate for NMT-driven pathology has not been established in human trials.

5.4 Liver Health: NASH and Lipotoxicity

Although myristic acid is a minor plasma fatty acid, it has attracted growing attention because of clinical evidence suggesting its ability to decrease HDL plasma levels and describing it as an independent predictor of nonalcoholic steatohepatitis (NASH), the most extreme form of nonalcoholic fatty liver disease.

Research has shown that myristic acid is a predictor of NASH and stimulates ceramide synthesis. Studies investigated the synergism between myristic acid and palmitic acid in ceramide synthesis, endoplasmic reticulum stress, lipotoxicity, and NASH, using primary mouse hepatocytes. Unlike palmitic acid, myristic acid alone was not lipotoxic, but it potentiated palmitic acid-mediated lipoapoptosis, ER stress, caspase-3 activation, and cytochrome c release.

Evidence strength assessment: The evidence linking myristic acid to NASH risk is largely observational (biomarker studies) and preclinical (cell-culture and animal models). No clinical trials have been conducted using isolated myristic acid supplementation to assess NASH outcomes in humans.

5.5 Omega-3 Status and Membrane Fluidity

Dabadie, Peuchant, Bernard, Leruyet, and Mendy (2005) reported that moderate myristic acid consumption improves long-chain omega-3 fatty acid levels in plasma phospholipids, which could exert improvement of cardiovascular health parameters in humans. Another study by the same group reported that the consumption of myristic acid from dairy fat increased HDL cholesterol and decreased triacylglyceride levels, while no changes in LDL cholesterol were observed. These studies used moderate dietary levels from dairy fat matrices and involved small samples of male monks without dyslipidaemia; their findings are preliminary and not replicated at scale.

5.6 Pharmaceutical and Topical Uses (Isopropyl Myristate)

Isopropyl myristate, the ester of myristic acid, is a polar emollient used in cosmetic and topical pharmaceutical preparations as a penetration enhancer where skin absorption is desired. It is also used as a treatment for head lice. In the technical literature, isopropyl myristate is the most commonly investigated fatty acid ester as a penetration enhancer in topical and transdermal formulations. DSC studies showed a decrease in enthalpy and a negative shift in the phase transition temperatures of stratum corneum lipids, indicating integration of isopropyl myristate within the lipid bilayer, which is associated with an increase in lipid fluidity.

6. Body Systems and Health Areas

• Cardiovascular system: Myristic acid is directly involved in post-translational protein changes and mechanisms that control important metabolic processes in the human body. At the population level, it is associated with modulation of LDL, HDL, and total cholesterol, with outcomes depending on dietary context and fatty acid substitution patterns.
• Cell signalling and protein biology: Myristoylation plays vital roles in cellular signalling, protein–protein interaction, and targeting of proteins to endomembrane and plasma membrane systems.
• Immune system: Research over the past three decades has led to understanding of the significance of protein myristoylation in regulating cellular signalling pathways, especially in carcinogenesis and more recently in immune function.
• Liver (hepatic metabolism): Myristic acid has been described as an independent predictor of nonalcoholic steatohepatitis (NASH), the most extreme form of nonalcoholic fatty liver disease.
• Skin and dermal: As isopropyl myristate, the compound functions as a pharmaceutical excipient to facilitate percutaneous drug absorption. Isopropyl myristate disrupts the lipid structure of the stratum corneum, allowing for increased drug permeation into deeper skin layers.

7. Dosage and Consumption Data from Studies

There is no established supplemental dose for myristic acid as an isolated dietary supplement. Intake figures reported in specific research contexts are as follows:

• In Dabadie et al. (2005), 25 male monks received isocaloric diets for 5 weeks each; in the first diet, 30% of calories came from fat with 8% from saturated fatty acids and 0.6% of total energy from myristic acid.
• In a subsequent 1-year study by the same group involving 29 monks, two experimental diets were tested for 3 months each: diet 1 delivered myristic acid at 1.2% of total energy (TE) and diet 2 at 1.8% TE, each associated with 0.9% TE of α-linolenic acid. A control diet provided myristic acid at 1.2% TE with only 0.4% TE of α-linolenic acid.
• Because of a lack of specific toxicity data for myristic acid, an exact tolerable intake cannot be defined; however, an estimated maximum intake from flavouring use is 35.07 mg/day or 0.58 mg/kg/day.
• For the derivative isopropyl myristate as a topical penetration enhancer, it is typically used in concentrations up to a few percent; for skin penetration enhancement, concentrations around 2% have shown efficacy.

There is no recommended supplemental dose of myristic acid as an isolated ingredient. Reasonable intake is framed within total saturated fat guidance rather than per-fatty-acid targets.

8. Safety Considerations

8.1 Acute Toxicity and Mutagenicity

Myristic acid has been shown to have a low order of acute oral toxicity in rodents. It may be irritating in pure form to skin and eyes under exaggerated exposure conditions, but is not known or predicted to induce sensitisation responses. Myristic acid did not induce a mutagenic response in either bacterial or mammalian systems in vitro.

For related fatty acid analogs, a NOEL (No Observable Effect Level) of >6,000 mg/kg was reported for lauric acid (12-carbon) following dietary exposure to male rats for 18 weeks, and a NOEL of >5,000 mg/kg was reported for palmitic acid (16-carbon) following dietary exposure to rats for 150 days.

8.2 Regulatory Safety Classification

Myristic acid is used in the food industry as a flavor ingredient and is found widely distributed in fats throughout the plant and animal kingdom, including common human foodstuffs such as nutmeg. The data available indicate that at current levels of intake, food flavouring use of myristic acid does not pose a health risk to humans. It is categorised as a natural fatty acid and may be safely used in food per FDA § 172.860 (2000).

8.3 Cardiovascular Risk Considerations

Myristic acid, the 14-carbon saturated fatty acid, is associated with an increased cardiovascular disease risk. It is correlated with an increase in plasma cholesterol and mortality due to cardiovascular diseases in some studies. However, as noted in the scientific evidence section, three prospective studies found no evidence for an association between circulating myristic acid and CHD risk in either direction. The overall picture of cardiovascular risk remains dependent on the dietary matrix and what myristic acid replaces.

8.4 Liver-Related Concerns

Myristic acid, a free fatty acid highly abundant in copra/palmist oils, is described as a predictor of nonalcoholic steatohepatitis (NASH) and stimulates ceramide synthesis. The mechanistic and epidemiological links to NASH are based on cell and biomarker studies; causal human interventional data are lacking.

8.5 Topical and Excipient Safety

Isopropyl myristate, the ester derivative of myristic acid, is determined safe for use in cosmetics according to the Cosmetic Ingredient Review (CIR) panel. Isopropyl myristate is widely recognised for its low toxicity and excellent safety profile in topical applications. Acute dermal toxicity tests reveal minimal irritation and low sensitisation potential; however, when used at high concentrations or under occlusive conditions, it may cause mild irritation due to increased skin penetration of other components.

8.6 Interactions and Special Populations

While myristic acid accumulates fat in the body, its consumption also impacts cardiovascular health in ways that are largely influenced by the balance between saturated fatty acid and simple dietary carbohydrates in the diet. No direct drug–nutrient interactions for myristic acid as an isolated supplement have been established in the reviewed literature. Individuals with dyslipidaemia, hepatic disease, or cardiovascular risk should be aware that high intake of myristic acid-rich foods (coconut oil, dairy fat) can influence plasma lipid profiles. The compound is not known or predicted to induce sensitisation responses in the general population.

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