IngredientsSphingomyelin (SM) is a type of sphingolipid found in animal cell membranes, especially in the membranous myelin sheath that surrounds some nerve cell axons. It usually consists of phosphocholine and ceramide, or a phosphoethanolamine head group; therefore, sphingomyelins can also be classified as sphingophospholipids. In humans, SM represents approximately 85% of all sphingolipids, and typically makes up 10–20 mol % of plasma membrane lipids.
The precise chemical structure of sphingomyelin—N-acyl-sphingosine-1-phosphorylcholine—was reported in 1927, and at the molecular level sphingomyelin comprises: (i) a C18-dominant sphingosine backbone; (ii) a saturated or monounsaturated C14–C26 fatty acyl chain linked at C2 to form ceramide; and (iii) a phosphorylcholine headgroup at C1.
Phosphosphingolipids such as sphingomyelins are formed when the head group such as phosphocholine is linked to the ceramide via a phosphodiester linkage. A ceramide is generated when a fatty acyl group is linked to the sphingoid bases through an amide-linkage. SM is a sphingolipid found in animal tissues, which consists of a phosphorylcholine head group, a long-chain fatty acyl group and a sphingosine. It predominantly colocalizes with cholesterol on the outer leaflet of the plasma membrane, lysosomal and Golgi membranes, as well as in lipoproteins.
The primary sources of polar lipids in the diet include milk, soybeans, fish and eggs. Sphingomyelins are high in animal-derived foods, such as aquatic products (2–10% of total phospholipids), meat products (5–10% of total phospholipids), eggs (approximately 1.5% of total phospholipids), and dairy products (approximately 25% of total phospholipids).
SM represents approximately 25% and 35% of the total polar lipid fractions of bovine and human milks, respectively. The total phospholipid content in human milk is 14.7–42.2 mg/100 mL (3.05–5.06 mg/g total lipid). SM is found to be the most abundant phospholipid in human breast milk (28.4–45.5% of the total phospholipid content), followed by phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and phosphatidylinositol.
Milk fat is an emulsion of natural oil and water, which mainly comprises triglycerides, phospholipids, cholesterol, and various lipids. Milk-fat globules are surrounded by the milk fat globule membrane (MFGM) derived from the membranes of mammary cells, and most MFGM products applied in studies come from bovine milk. Compared with other animal-derived phospholipids containing lower than 5% sphingomyelin or plant-derived phospholipids without sphingomyelin, MFGM extracts have received widespread attention as a potential nutrient, especially their natural phospholipid composition.
Eggs represent an alternative source of SM to milk, making up 2–3% of the polar lipid fraction, which are located almost exclusively in the yolk. The total amounts of sphingolipids in food vary considerably, from a few micromoles per kilogram (fruits) to several millimoles per kilogram in rich sources such as dairy products, eggs and soybeans. With the use of the limited data available, per capita sphingolipid consumption in the United States can be estimated to be on the order of 150–180 mmol (approximately 115–140 g) per year, or 0.3–0.4 g/day.
Unlike the widely studied milk triglycerides, which comprise most milk lipids (~98%), sphingolipids such as sphingosine, ceramide, glycosylated ceramides, and sphingomyelin represent only a minor portion of the total (typically 0.5–1%).
Sphingomyelin obtained from natural sources, such as eggs or bovine brain, contains fatty acids of various chain length. Sphingomyelin with set chain length, such as palmitoylsphingomyelin with a saturated 16 acyl chain, is available commercially.
The milk fat globule membrane (MFGM) comprises a core of triglycerides surrounded by a structural membrane composed of phospholipids, cholesterol, proteins, and glycoproteins. MFGM concentrates and powders derived from bovine whey processing are the primary commercial forms through which sphingomyelin is delivered as a functional food ingredient or dietary supplement. Sphingomyelin is contained largely in the MFGM surrounding milk fat, and concentrated fractions of which are also generated concurrently during the manufacture of dairy products. Such an SM-containing milk phospholipid concentrate (SM-MPC) is useful for investigating the benefits of dietary SM.
Sphingolipids are a greatly conserved category of lipids, which were discovered in the brain by Johann Ludwig Wilhelm Thudichum more than a century ago. He laboriously characterized and purified 140 distinct chemicals from bovine and human brains. His classic work A Treatise on the Chemical Constitution of the Brain (1884) described how he discovered and named phospholipids, cephalin, and sphingomyelin.
Sphingomyelin was first catalogued by German biochemist Johann Ludwig Wilhelm Thudichum (1829–1901) as part of his pioneering research into the chemical properties of the central nervous system. Thudichum observed that sphingomyelin, although found in all types of cells, was particularly abundant in the cell membrane sheaths insulating nerve cells. Initially, sphingomyelin was considered crucial to the cell's intricate network of communication relays, although its specific function was not defined.
During years of meticulous spectroscopic analyses, Thudichum showed that the substance then known as "protagon" was in fact a mixture of lipids in the brain: sphingomyelin, sulphatides, galactocerebrosides, ethanolamine, lecithins, and cephalins.
Evidence for the isolation of sphingolipids from the brain stems from the late 19th century (1884) by Thudichum, who introduced the name "sphingosin," named after the mythical sphinx, owing to their enigmatic nature. In later years, the chemical structure of sphingosines, the building blocks of all sphingolipids, was elucidated, followed by the discovery of different classes of complex sphingolipids, including sphingomyelins and glycosphingolipids.
Following their discovery in the brain and first description in 1884 by Thudichum, sphingolipids were largely overlooked for almost a century, perhaps due to their complexity and enigmatic nature. It was with the discovery of sphingolipidoses—a series of inherited diseases caused by mutations of enzymes involved in sphingolipid degradation—that sphingolipids returned to the limelight. The essential breakthrough came decades later in the 1990s with the discovery that sphingolipids are not just structural elements of cellular membranes, but they are also intra- and extracellular signaling molecules.
There is no historical record of sphingomyelin being used as a discrete therapeutic preparation in any traditional medicine system (Ayurveda, Traditional Chinese Medicine, European herbalism, or indigenous pharmacopeias). The compound was not isolatable from food without modern biochemical techniques, and its recognition as a bioactive dietary constituent is entirely a product of 20th- and 21st-century science. As research advanced, particularly during the quest for AIDS treatments starting in the early 1990s, scientists began to explore how sphingomyelin is linked to cell death processes.
In the endoplasmic reticulum (ER), serine palmitoyltransferase (SPT) condenses serine with palmitoyl-CoA to form 3-ketosphinganine, which is reduced to dihydrosphingosine (sphinganine). Chain-length–specific ceramide synthases (CerS1–6) then N-acylate sphinganine with saturated or monounsaturated C14–C26 fatty acids to generate dihydroceramide, which DEGS1 desaturates to ceramide. Ceramide is ferried—largely by CERT—to the Golgi, where sphingomyelin synthase (SMS1/2) transfers phosphocholine from phosphatidylcholine to ceramide, yielding sphingomyelin and diacylglycerol (DAG).
Dietary sphingomyelin (SM) is hydrolyzed by intestinal alkaline sphingomyelinase and neutral ceramidase to sphingosine, which is absorbed and converted to palmitic acid and acylated into chylomicron triglycerides. SM digestion is slow and is affected by luminal factors such as bile salts, cholesterol, and other lipids. In the gut, SM and its metabolites may influence triglyceride hydrolysis, cholesterol absorption, lipoprotein formation, and mucosal growth.
Lipid rafts are distinct plasma membrane microdomains comprised of cholesterol tightly packed with sphingolipids, in particular sphingomyelin, creating a liquid-ordered domain within the liquid-disordered bulk plasma membrane. Rafts differ in their protein and lipid composition from the surrounding membrane, housing signaling molecules including multiple glycosylphosphatidylinositol (GPI)-anchored proteins, doubly-acylated tyrosine kinases of the Src family, and transmembrane proteins. In addition, rafts serve as sites that multiple receptors translocate into or out of upon their activation, and recent evidence suggests that these translocation events are crucial for multiple signal transduction cascades.
The quasi-cylindrical geometry of sphingomyelin packs tightly with cholesterol to form lipid rafts that cluster receptors and signaling proteins—one reason sphingomyelin is central to membrane order and receptor signaling.
Acid sphingomyelinase (ASM; EC 3.1.4.12) is one member of a family of enzymes that catalyzes the breakdown of sphingomyelin by cleavage of the phosphorylcholine linkage, thereby producing ceramide. This causes reorganization of membrane lipid microdomains, or "raft" structures, and stimulates downstream signaling events. One product of sphingomyelin hydrolysis by ASM is the lipid ceramide, an important signaling molecule that is elevated in many common diseases (e.g., diabetes, fibrosis, sepsis).
SM and its metabolites, including sphingoid bases, ceramide (Cer), ceramide-1-phosphate (C1P), and sphingosine-1-phosphate (S1P), play an important role in human health. The diverse structures of sphingolipids elicit various functions in cellular membranes and signal transduction, which may affect cell growth, differentiation, apoptosis, and maintain biological activities.
SM accounts for approximately 20% of the phospholipids in human plasma lipoproteins, of which two-thirds are in LDL and VLDL. It is secreted in chylomicrons and VLDL and transferred into HDL via the ABCA1 transporter.
Natural phospholipids, especially sphingomyelin, have high affinity for cholesterol to slow the rate of luminal hydrolysis, micellar solubilization, and transfer of micellar lipids to the enterocytes. Interestingly, sphingomyelin from milk is more effective in inhibiting cholesterol absorption than that from eggs, which may be attributed to the higher degree of saturation and longer chain length of the fatty acyl group in milk sphingomyelin.
In a human crossover clinical trial (registered as ClinicalTrials.gov #NCT00328211), a specific study investigated whether dietary SM supplementation affected cholesterol absorption in human subjects. The conclusion was that in humans, 1 g/day of dietary SM does not alter the blood lipid profile except for an increased HDL-cholesterol concentration and has no effect on cholesterol absorption, synthesis and intraluminal solubilization compared to control. This finding is an important caveat to the more robust effects observed in animal models, underscoring the gap between preclinical and human evidence.
A comprehensive search was performed to retrieve randomized controlled trials conducted between 2003 and 2023 to examine the effects of dietary SM supplementation on metabolic parameters in the Cochrane Library, PubMed, Web of Science, Embase, and ClinicalTrials.gov databases. When compared to the control, SM supplementation reduced the blood total cholesterol level (MD: −12.97 mg/dL, 95% CI: −14.57 to −11.38; p < 0.00001), low-density lipoprotein cholesterol level (MD: −6.62, 95% CI: −10.74 to −2.49; p = 0.002), and diastolic blood pressure (MD: −3.31; 95% CI: −4.03 to −2.58; p < 0.00001). Overall, dietary SM supplementation had a protective effect on blood lipid profiles and insulin level, but had limited impacts on other metabolic parameters in adults without metabolic syndrome. The authors noted that more clinical trials and basic research are required. These pooled results should be interpreted cautiously because the number of eligible RCTs was small and studies varied in design and SM source.
Sphingomyelin (SM) levels in the circulation correlate positively with atherosclerosis burden. SM is a ubiquitous component of human diets, but it is unclear if dietary SM increases circulating SM levels. This distinction—between endogenous circulating SM (which is elevated in atherosclerosis) and dietary SM supplementation (which may have protective effects)—is a critical conceptual point in the literature.
Several clinical trials have highlighted the role of sphingolipids in atherosclerosis, reporting increased plasma concentrations of ceramides, sphingomyelins, sphinganine, and sphingosine in patients with coronary artery disease (CAD). In an observational study of 732 subjects undergoing coronary angiography, SM levels were significantly correlated with triglyceride levels (r = 0.10, p = 0.005), apoB (r = 0.13, p = 0.001), apoE (r = 0.135, p < 0.001), fibrinogen levels (r = 0.11, p = 0.006), and left ventricular ejection fraction (r = −0.201, p < 0.001).
The production of endogenous sphingomyelin is linked to pathological changes in obesity, diabetes, and atherosclerosis. However, dietary supplementations of sphingomyelin and its metabolites have been shown to maintain cholesterol homeostasis and lipid metabolism, and to prevent or treat these diseases. This distinction between endogenous overproduction and dietary intake is important: the two appear to have opposing net effects in experimental models.
In mouse studies, SM consumption did not increase circulating SM levels or atherosclerosis in high-fat–fed apoE−/− mice. Serum TMAO levels in C57BL/6 mice were low and had no effect on atherosclerosis lesion development. Dietary SM supplementation significantly reduced atherosclerotic lesion area in the aortic arch of chow-fed apoE−/− mice. This study established that dietary SM does not affect circulating SM levels or increase atherosclerosis in high-fat–fed apoE−/− mice, but it is anti-atherogenic in chow-fed apoE−/− mice. These findings are preclinical and cannot be directly applied to humans without further RCT confirmation.
Sphingomyelin (SM) supports brain myelination, a process closely associated with cognitive maturation. The presence of SM in breast milk suggests a role in infant nutrition. SM is the most abundant sphingolipid that plays a vital role as a structural component found in mammalian cell membranes. Sphingomyelin content in mammals ranges from 2 to 15% in most tissues, with higher concentrations found in nerve tissues, red blood cells, and the ocular lenses.
Researchers investigated the link between early life dietary SM, later cognitive development, and myelination using an exploratory observational study of neurotypical children. SM levels were quantified in infant nutrition products fed in the first three months of life and associated with myelin content (brain MRI) as well as cognitive development (Mullen scales of early learning; MSEL).
Cross-sectional findings showed a correlation between sphingomyelin levels present in the infant nutrition products and brain myelin water fraction in multiple brain regions at 12–24 months of age. Specifically, higher levels of sphingomyelin in the products were correlated with higher levels of myelin in these brain regions. Higher levels of SM were significantly associated with higher rates of change in verbal development in the first two years of life (r = 0.65, p < 0.001), as well as higher levels of myelin content at 12–24 months.
Only one dietary intervention study had evaluated the effect of SM supplementation on cognition in human infants at that time of the 2019 publication. In a sample of low-birth weight infants, the feeding of SM-fortified infant formula (20% vs. 13% of total milk phospholipids) in the first eight weeks of life resulted in increased plasma and erythrocyte SM levels at four, six, and eight weeks of life. In addition, the same study reported improved behavior rating scores, better novelty preference scores, lower latency of visual evoked potentials, and increased sustained attention scores at 12 and/or 18 months of age; no differences were found for overall neurodevelopment scores.
In vitro data showed SM treatment resulted in increased proliferation, maturation, and differentiation of oligodendrocyte precursor cells (OPCs), as well as increased axon myelination. These findings indicate an impact of dietary SM on cognitive development in healthy children, potentially modulated by oligodendrocytes and increased axon myelination.
Children who received infant formula with added MFGM showed improved myelination in motor-related areas (motor cortices, internal capsule, and cerebellum) and improved MSEL gross and fine motor scores. No significant differences in verbal or overall cognitive ability scores were noted. These results support the importance of phospholipids, sphingolipids, and sphingomyelin in promoting brain myelination and cognitive development.
Evidence strength assessment: Future research should include randomized controlled trials to substantiate the efficacy of SM for cognitive benefits, together with preclinical studies examining SM bioavailability and brain uptake. Current human evidence in this area ranges from observational to very small interventional studies; the evidence is promising but remains preliminary.
Sphingomyelin (SM) hydrolysis generates biologically active products regulating cell growth, differentiation, and apoptosis. Dietary SM has been found to inhibit colonic tumorigenesis. Alkaline sphingomyelinase (alk-SMase) is the key enzyme responsible for sphingomyelin digestion in the gut. Dietary SM inhibited tumorigenesis and increased the alk-SMase activity in the colon by 65%, and the increased activity was associated with increased enzyme protein and mRNA expression (in carcinogen-challenged ICR mice fed SM at 0.5 g/kg in diet for 22 weeks).
Marked reductions of alkaline sphingomyelinase enzyme activity have been found in sporadic colorectal carcinomas and in both adenomas and flat mucosa of patients with familial adenomatous polyposis, indicating an anti-proliferative role in colonic cell growth. Alkaline SMase, at doses that induce SM hydrolysis, inhibits growth of colon cancer cells. The inhibition is attributed to an anti-proliferative effect rather than an apoptotic effect.
Evidence strength assessment: Evidence for sphingomyelin's role in colorectal cancer prevention is derived almost entirely from animal models and cell lines. No human clinical trials have directly tested dietary SM supplementation for colorectal cancer prevention or treatment.
Enhanced levels of SM, ceramide, sphingosine-1-phosphate, and ceramide-1-phosphate and decreased levels of cerebrosides and gangliosides were found in rodent studies of dextran sulfate sodium colitis. Moreover, high levels of SM and ceramide have been detected in ilea of Crohn's disease patients. The relationship between sphingolipid levels and intestinal inflammation is complex and has not yet been translated into clinical interventional evidence with dietary SM specifically.
Ceramides are among the lipids that make up sphingomyelin, which is a major component of the lipid bilayer that forms cell membranes of cells in the stratum corneum. Thus, ceramides are lipophilic and likely to be absorbed into the skin. However, they are expected to remain in the stratum corneum and not penetrate any deeper.
Data from several animal studies and clinical trials have shown the benefits of consumption of food-derived sphingomyelin and its metabolites on skin health, including those derived from plants, animals, and marine species. In comparison to control mice, supplementation of sphingomyelin (146 mg/kg body weight/day) considerably reduced covalently bound ω-hydroxy ceramides and significantly attenuated an increase in transepidermal water loss (TEWL).
In a double-blind, placebo-controlled, randomized trial examining oral sphingomyelin supplementation and skin condition: Ninety-six healthy subjects aged 20 to 39 years with low skin hydration were randomly assigned to three groups: a high-SM group supplemented with SM-containing milk phospholipid concentrate (SM-MPC) at a dose equivalent to 10 mg/day of SM, a low-SM group supplemented with SM-MPC equivalent to 5 mg/day of SM, and a placebo group. During daily supplementation for 12 weeks, parameters related to the condition of skin were evaluated at baseline and every 3 weeks. This trial represents the type of human evidence available for the skin health benefit; however, it used a full milk phospholipid concentrate rather than isolated SM, making it difficult to attribute effects to SM alone. Evidence in this area is early-stage.
Bovine milk sphingolipids have received attention in basic research and clinical science because of their ability to modulate microbial and host metabolism and physiology, including hypolipidemic effects on circulating and hepatic lipids, anti-inflammatory actions, the ability to modulate the microbiome to protect against gut dysbiosis, and even the potential to improve neurobehavioral development in human infants.
Dietary supplementation with egg SM reduces plasma cholesterol and triglyceride levels in hyperlipidemic APOE*3 Leiden mice. It also decreases hepatic steatosis in Zucker fatty rats. A high-fat diet supplemented with SM dose-dependently reduces hepatic steatosis in C57BL/6 mice. These findings are limited to animal models.
The underlying mechanism of dietary SM's effect on atherosclerosis is not fully clear, but circulating lipid and TMAO levels were not affected by SM supplementation, suggesting that dietary SM may modulate gut flora composition. A recent study reported that 4 weeks of dietary supplementation with 0.25% (wt/wt) SM selectively increases the abundance of Bifidobacterium and attenuates obesity, metabolic syndrome, and macrophage activation in C57BL/6 mice. Human microbiome research in this context is not yet available.
There is no official recommended daily allowance or upper safe limit for sphingomyelin.
The following are dosages specifically reported in peer-reviewed studies:
Supplement products supplying MFGM typically deliver sphingomyelin within a broader phospholipid matrix. Isolated SM capsules or powders are not subject to any formal pharmacopeial dosage standards.
There is no known nutritional requirement for sphingolipids; nonetheless, they are hydrolyzed throughout the gastrointestinal tract to the same categories of bioactive metabolites. Dietary sphingomyelin at food-relevant quantities is a normal constituent of the human diet and has been consumed throughout human evolutionary history.
Topical use of ceramide as supplementation is mostly considered safe for short- and long-term use, as most ceramides were reported to have no acute toxicity, be non-irritant and non-mutagenic, with overall little to no observable adverse effects. Both oral and dermal doses to avoid acute toxicity from ceramide supplementation were found to be reasonably high.
Sphingomyelin is particularly notable for its involvement in Niemann-Pick disease, which arises from its accumulation in the liver, spleen, or lungs of newborns. This genetic disorder (Niemann-Pick types A and B) results from deficiency of acid sphingomyelinase; it is not caused or worsened by dietary SM intake, but represents a critical safety concern if patients with such disorders were to use concentrated SM supplements. Acid sphingomyelinase catalyzes the breakdown of sphingomyelin by cleavage of the phosphorylcholine linkage, thereby producing ceramide.
Dietary choline increases atherosclerosis by raising circulating trimethylamine N-oxide (TMAO) levels in mice and humans. As SM has a choline head group, the question arises as to whether dietary SM accelerates atherosclerotic lesion development by increasing circulating SM and TMAO levels. However, mouse model evidence suggests that unlike free choline, SM consumption did not increase circulating SM levels or atherosclerosis in high-fat–fed apoE−/− mice, and serum TMAO levels in C57BL/6 mice were low and had no effect on atherosclerosis lesion development. Whether this finding generalizes to humans has not yet been definitively established in clinical studies.
Endogenous SM is involved in metabolic syndrome, while dietary SM supplementation may maintain lipid metabolism and prevent or alleviate metabolic syndrome. This apparent paradox—elevated circulating SM is a cardiovascular biomarker of risk, yet dietary SM supplementation appears protective in some models—is an active area of investigation and means that individuals with established dyslipidemia or cardiovascular disease should approach high-dose SM supplementation with caution pending further human evidence.
The majority of commercial sphingomyelin supplements and MFGM concentrates are derived from bovine milk; individuals with milk protein allergies should exercise caution. The avian egg yolk (including chicken, duck, goose, turkey, and quail) contains abundant phospholipids, and egg-derived SM would be contraindicated in individuals with egg allergy.
No formal drug interaction studies on dietary sphingomyelin have been identified in the peer-reviewed literature as of the available sources. The choline-containing head group theoretically places SM in a class of nutrients that may interact with the gut-flora pathways governing TMAO production, though the available mouse data suggest SM produces less TMAO than equivalent free choline. Individuals taking lipid-modifying agents (such as statins or bile acid sequestrants) may experience altered interactions with dietary SM through shared lipid absorption pathways; however, no clinical drug-interaction data were identified in the searched literature.
Health conditions that Sphingomyelin may help support.
Body systems that Sphingomyelin may help support.
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