Lecithin

Lecithin

1. Identity, Chemical Nature, and Forms

Nomenclature and chemical identity. Lecithin (pronounced /ˈlɛsɪθɪn/; from Ancient Greek λέκιθος, meaning "yolk") is a generic term designating a group of yellow-brownish fatty substances occurring in animal and plant tissues which are amphiphilic — they attract both water and fatty substances — and are used for smoothing food textures, emulsifying, homogenizing liquid mixtures, and repelling sticking materials. The word lecithin originated from the Greek lekithos, referring to egg yolk.

Constituent phospholipids. Lecithins are mixtures of glycerophospholipids including phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylserine, and phosphatidic acid. Lecithin is a phospholipid mixture of acetone-insoluble phosphatides consisting mainly of phosphatidylcholine, phosphatidyl ethanolamine, phosphatidyl serine, and phosphatidyl inositol combined with various other substances, including fatty acids and carbohydrates. More broadly, lecithin is a generic term used for the description of a multi-component blend of lipids — triglycerides, fatty acids, sterols, glycolipids, and phospholipids — which are structural and functional components of a diverse range of cell membranes for plants as well as for various terrestrial and marine animals.

Composition of commercial soy lecithin. Commercial soybean lecithin commonly comprises from about 50 to about 65% by weight of phosphatides, from about 30 to about 40% triglycerides and other lipids, and smaller amounts of other components such as sugars. The phosphatides comprise mainly phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI), and phosphatidic acid (PA), each commonly present in amounts of from about 8% to about 20% by weight of the lecithin, along with smaller amounts of phosphatidylserine.

Natural sources. Common sources include egg yolk, marine foods, soybeans, milk, rapeseed, cottonseed, and sunflower oil. The most studied source of lecithin is soybean, followed by sunflower and egg yolk. Although lecithin is present in most living organisms, its chemical and physical characteristics can vary considerably, depending on the origin and the extraction process.

Extraction and preparation. Lecithin can easily be extracted chemically using solvents such as hexane, ethanol, acetone, petroleum ether, or benzene; or extraction can be done mechanically. The lecithin can be obtained by water degumming the extracted oil of seeds. For sunflower lecithin, the extraction process is typically gentler and is carried out by cold pressing rather than with chemical solvents.

Commercial forms. Lecithin can be prepared in fluid and de-oiled forms. Fluid lecithin products are blends of phospholipids and vegetable oils. Refined lecithins with high levels of phospholipids (greater than 95%), prepared by acetone and alcohol fractionation, are soft, yellow-brown powders. Dietary supplement preparations include softgel capsules, granules, liquid/oil form, and powder. Lecithin is sold as a food additive and dietary supplement, and in cooking it is sometimes used as an emulsifier and to prevent sticking.

2. Historical Discovery and Traditional Use

Discovery. Lecithin was first isolated in 1845 by the French chemist and pharmacist Théodore Gobley. In 1850, he named the phosphatidylcholine lécithine. Gobley isolated it in egg yolk and established the complete chemical formula of phosphatidylcholine through research spanning 1845–1874.

Early European research and therapeutic interest. The world's earliest research on and production of lecithin and soy lecithin was done in Europe, with first France, then Germany leading the way. Starting in the mid-1920s, at the same time that therapeutic uses of soy lecithin were attracting considerable interest, much more important research on food and industrial applications was getting underway, mostly in Germany. By 1939 more than a thousand new uses for lecithin had been discovered, and many had been patented.

Industrial-scale production. The industrial production of lecithin started in the 1920s when the Bollmann extraction process enabled large quantities of lecithin to be obtained from soybeans instead of eggs. This paved the way for the production of various lecithins of different plant origins for a wide variety of uses.

Interest in East Asia. Although lecithin was first discovered and developed in Europe, it attracted interest in East Asia at a relatively early date. The earliest reference seen was in 1897 when Hanai, a Japanese agricultural chemist, wrote a 4-page article in English titled "Physiological Observations on Lecithin," in which soybeans were said to be a good concentrated source.

Twentieth-century therapeutic claims and the health food era. Many of the early US studies on the therapeutic value of lecithin were concerned with its ability to combat arteriosclerosis and reduce serum cholesterol levels. During the early 1940s, when extensive research began, it was noted that lecithin, originally present in many traditional whole and unprocessed foods, was increasingly removed or altered by modern refining techniques. Lecithin, like many other newly discovered foods of the 1920s and 1930s, went on to become a minor "superfood craze." By the 1960s and 1970s, it was being promoted in cookbooks as a panacea for any number of widely suffered maladies. Lecithin has been proposed for use in treating liver ailments, hypercholesterolemia, and neurologic diseases.

Early human cholesterol research. In 1943, Adlersberg and Sobotka reported striking decreases in serum cholesterol levels in five human patients receiving 12–15 grams daily of unrefined soy lecithin in the diet for 2–3 months.

3. Key Constituents and Mechanisms of Action

3.1 Phosphatidylcholine as the Principal Active Component

The phospholipid phosphatidylcholine (lecithin) is the major dietary source of choline, a semiessential nutrient that is part of the B-complex vitamin family. Choline has various metabolic roles, ranging from its essential involvement in lipid metabolism and cell-membrane structure to its role as a precursor for the synthesis of the neurotransmitter acetylcholine. Phosphatidylcholine is the most abundant among phospholipids in a human body and is a major component of cell membranes.

3.2 Cholinergic Neurotransmission

Lecithin (phosphatidylcholine) is a precursor for choline. As such, it is involved in the synthesis of the neurotransmitter acetylcholine, and levels of lecithin correlate with levels of choline and acetylcholine. Consequently, one presumed mechanism of action of lecithin is the increase in the synthesis, release, and availability of acetylcholine. Choline-containing phospholipids such as phosphatidylcholine or lecithin are acetylcholine precursors that easily traverse the blood-brain barrier. They act through two separate mechanisms of action: first, as substrate for acetylcholine synthesis, which can improve cholinergic neurotransmission. They may also have significant neuroprotective benefits in addition to serving as precursors, by maintaining and supplying the membrane structure of neurons.

3.3 Membrane Structure and Cellular Signaling

Lecithin is also involved in complex intracellular processes, including the regulation of cellular membrane permeability. Lecithin plays an important role in normal metabolism, for example by forming part of membrane phospholipids; some metabolites are messengers in cells; choline derived from lecithin plays a role in brain cells in the resynthesis of new phosphatidylcholine molecules needed for cells that envelop the axons of neurones; and choline apparently has a protective role, allowing cells to die rather than to turn malignant when they undergo mutations.

3.4 Methyl Group Donation and Homocysteine Metabolism

Choline and some of its metabolites, such as betaine, can serve as a source of methyl groups that are required for proper metabolism of certain amino acids, such as homocysteine and methionine. The pathways of choline and one-carbon metabolism intersect at the formation of methionine from homocysteine. Methionine is regenerated from homocysteine in a reaction catalyzed by betaine:homocysteine methyltransferase, in which betaine, a metabolite of choline, serves as the methyl donor.

3.5 Lipid Emulsification and Bile Metabolism

Lecithin has low solubility in water but is an excellent emulsifier. In aqueous solution, its phospholipids can form either liposomes, bilayer sheets, micelles, or lamellar structures, depending on hydration and temperature, resulting in a type of surfactant that is classified as amphipathic. The emulsifying properties of lecithin in the gut are believed to facilitate lipid absorption and modify cholesterol transport through interaction with biliary metabolism.

3.6 Lecithin:Cholesterol Acyltransferase (LCAT) and Reverse Cholesterol Transport

Lecithin cholesterol acyltransferase (LCAT) plays an important role in the reverse cholesterol transport (RCT) process, contributing to the removal of surplus cholesterol from cells. LCAT cleaves the fatty acid from the sn-2 position of phosphatidylcholine and then transesterifies it to the A-ring of cholesterol, producing lysophosphatidylcholine and cholesteryl ester. The role of LCAT in cardiovascular disease has been extensively studied; although there has been much recent progress in the biochemistry of LCAT and its effect on HDL metabolism, its role in the pathogenesis of atherosclerosis is still not fully understood.

3.7 The TMAO Pathway: A Dual-Edged Mechanism

Ingested phosphatidylcholine (lecithin), the major dietary source of total choline, is acted on by intestinal lipases to form a variety of metabolic products. Recent studies in animals have shown a mechanistic link between intestinal microbial metabolism of the choline moiety in dietary phosphatidylcholine (lecithin) and coronary artery disease through the production of a proatherosclerotic metabolite, trimethylamine-N-oxide (TMAO). Compelling evidence suggests that circulating TMAO might advance atherosclerosis by disturbing the clearance of cholesterol in the liver, and higher blood TMAO concentrations have been related to an increased risk of CVD and mortality. Other putative mechanisms may involve upregulation of macrophage scavenger receptors, augmented macrophage cholesterol accumulation, and foam cell formation, which result in increased inflammation and oxidation of LDL cholesterol.

3.8 Pharmacokinetics

Little is known about the pharmacokinetics of lecithin. Following ingestion, the lipid is absorbed from the small intestine and may enter the lymph system, as well as systemic blood circulation. Among lecithins, phosphatidylcholine is hydrolysed to choline in the cytidine-5-diphosphate-choline pathway in all cells of the body.

4. Scientific Evidence by Area of Use

4.1 Cardiovascular Health and Lipid Profile

Clinical evidence. A 1986 human study by Brook, Linn, and Aviram published in Biochemical Medicine and Metabolic Biology enrolled patients with hypercholesterolemia and hypertriglyceridemia. Nine patients with type IIa hyperlipoproteinemia and nine patients with type IV hyperlipoproteinemia were given soya lecithin 12 g/day for 3 months. Plasma cholesterol and triglycerides were reduced by 15% and 23%, respectively, and HDL-cholesterol increased by 16% in the hypercholesterolemic patients. Platelet function was unchanged. In the hypertriglyceridemic patients, total cholesterol fell by 18%, triglycerides by 36%, and HDL-cholesterol increased by 14%, with a 27% reduction in platelet aggregation. In the hypertriglyceridemic patients who received increasing doses of 6, 12, and 18 g/day over one-month periods, the optimal lipoprotein-lowering effect was achieved with a daily dose of 12 g soya lecithin per day.

A 2010 human clinical study published in Cholesterol (Mourad et al.) examined soy lecithin in hypercholesterolemic patients. One soy lecithin capsule (500 mg) was administered daily. The results showed a reduction of 40.66% and 42.00% in total cholesterol and of 42.05% and 56.15% in LDL cholesterol after treatment for one and two months, respectively. A significant reduction in total cholesterol and LDL-cholesterol concentrations was observed during the first month of treatment, suggesting that the administration of soy lecithin daily may be used as a supplemental treatment in hypercholesterolemia.

Cardiovascular risk — the TMAO concern. A landmark study published in the New England Journal of Medicine (2013) investigated the intestinal microbial metabolism of phosphatidylcholine in human subjects. The investigators examined the relationship among intestinal microbiota-dependent metabolism of dietary phosphatidylcholine, TMAO levels, and adverse cardiovascular events in humans, quantifying plasma and urinary levels of TMAO after a phosphatidylcholine challenge in healthy participants before and after suppression of intestinal microbiota with oral broad-spectrum antibiotics. A prospective study of over 120,000 subjects from the Nurses' Health Study and the Health Professionals Follow-Up Study further examined dietary phosphatidylcholine intake. The evidence for an association of dietary phosphatidylcholine with CVD and mortality is described as limited. Circulating TMAO has been related to cardiovascular diseases and mortality, and previous research suggested that the relation of TMAO with CVD risk might be stronger in diabetic than in nondiabetic populations.

Strength of evidence: Some human clinical trials show favorable lipid effects, particularly reductions in LDL and triglycerides and increases in HDL. However, overall evidence is mixed, studies are generally small and of variable quality, and the TMAO pathway introduces a plausible cardiovascular risk signal from the same compound, particularly in individuals with dysbiotic gut microbiota. While studies suggest a positive correlation between increased LCAT activities, reduced LDL particle size, and elevated serum levels of triglyceride-rich lipoprotein markers in individuals at risk of ASCVD, the review acknowledges existing controversies.

4.2 Cognitive Function, Dementia, and Neurological Disease

Rationale. The cholinergic hypothesis of Alzheimer's disease predicts that supplements providing choline precursors might improve cholinergic neurotransmission. A loss of choline-containing phospholipids contributes to the development of neurodegenerative diseases such as Alzheimer's disease, multiple sclerosis, and Parkinson's disease.

Cochrane Review — dementia and cognitive impairment. A Cochrane systematic review (Higgins & Flicker, 2000) examined the evidence from all available randomized controlled trials. The Cochrane analysis selected 12 randomized trials involving patients with Alzheimer's disease (265 patients), Parkinsonian dementia (21 patients), and individual memory problems (90 patients). No trials reported any clear clinical benefit of lecithin for Alzheimer's disease or Parkinsonian dementia. Only a few trials contributed data to meta-analyses. The review concluded that evidence from randomized trials does not support the use of lecithin in the treatment of patients with dementia. A moderate effect cannot be ruled out, but results from the small trials to date do not indicate priority for a large randomized trial.

A variety of RCTs have generally failed to successfully treat Alzheimer's or cognitive aging with lecithin, phosphatidylcholine supplements, or krill oil, although one or two trials reported some minimal effect. No benefits of any kind were reported in the Alzheimer's or Parkinson's patients; some benefits were reported in the one trial with subjective memory impairment, but these effects have not been replicated. The trials, although not promising, have all been short term, and longer-term trials could theoretically allow for more benefit.

Acetylcholine precursors such as phosphatidylcholine have been shown to prolong the favorable effects of acetylcholinesterase inhibitors on cognitive and behavioral improvements in patients with Alzheimer's disease and mild to moderate vascular dementia in some studies.

Strength of evidence: The Cochrane review represents the highest-quality synthesis available and does not support lecithin as a clinically effective treatment for dementia or Alzheimer's disease. Evidence for cognitive enhancement in healthy individuals or those with subjective memory complaints is weak and not replicated.

4.3 Liver Health and Hepatoprotection

Mechanistic basis. Choline is essential for liver function, and choline deficiency is associated with the induction of fatty liver disease. As such, the maintenance of adequate choline levels likely plays a greater role in the prevention of fatty liver disease than as a therapeutic option for established disease.

Clinical use of essential phospholipids. Preparations of essential phospholipids, containing soybean-derived polyenylphosphatidylcholine, have been tested in clinical studies for patients with liver disease. Essential phospholipids are recommended in the treatment of non-alcoholic fatty liver disease (NAFLD) in Russia, China, Latvia, and Poland.

A human study involving parenteral nutrition patients reported that patients treated with normal intravenous solutions with lipid emulsions developed fatty liver and liver dysfunction. Investigators found that giving phosphatidylcholine as an oral supplement completely reversed the fatty liver, and in the people given placebo, there was no reversion of fatty livers. This was interpreted as evidence that total parenteral nutrition is not delivering enough choline, leading to deficiency.

Strength of evidence: Preclinical (animal) evidence for lecithin's hepatoprotective role is relatively robust. Essential phospholipids are widely used in several countries as a hepatoprotective agent and are generally considered safe; however, safety data in clinical studies using essential phospholipids is poorly reported, and the most commonly reported adverse events are mild gastrointestinal events. Well-controlled large human RCTs specifically for lecithin supplementation and established liver disease remain limited.

4.4 Breastfeeding and Lactation

Lecithin is a mixture of choline, choline esters, fatty acids, glycerol, glycolipids, triglycerides, phosphoric acid, and phospholipids, such as phosphatidylcholine, that are normal components of human milk. Supplemental lecithin has been recommended as a treatment for plugged milk ducts. A meta-analysis found no evidence that high doses of lecithin improved milk flow in breast-feeding mothers or infants, though it concluded that "higher maternal choline intake was likely to be associated with better child neurocognition and neurodevelopment." There is no robust, scientifically validated clinical research investigating the safety and effectiveness of high-dose lecithin supplementation in lactating women and their infants.

Strength of evidence: Evidence for lecithin's use in preventing plugged ducts or mastitis is based largely on clinical observation and extrapolated from its biochemical role in milk fat emulsification. Controlled human trial data are lacking.

4.5 Bipolar Disorder and Psychiatric Uses

Patients with bipolar disorder reveal altered membrane phospholipid metabolism, and low choline levels within the orbital frontal gray matter have been found in patients with manic symptoms. Supplementation with lecithin apparently stabilizes the membrane and changes action potential. Lecithin has historically been investigated as an adjunctive treatment in manic-depressive illness based on its cholinergic properties, but high-quality human clinical data are limited.

Strength of evidence: Preliminary and based primarily on observational and mechanistic data. No large, well-designed RCTs have demonstrated clinical efficacy for psychiatric indications.

5. Body Systems Associated with Lecithin

• Central nervous system: Precursor to acetylcholine; involved in membrane integrity of neurons; investigated in dementia, cognitive impairment, and mood disorders.
• Cardiovascular system: Involved in lipoprotein metabolism and reverse cholesterol transport via LCAT; metabolized to TMAO via gut microbiota, which may have cardiovascular implications.
• Hepatobiliary system: Essential for normal hepatic fat metabolism; choline deficiency causes hepatic steatosis; phosphatidylcholine preparations used as hepatoprotective agents in multiple countries.
• Gastrointestinal system: Emulsifying properties facilitate lipid digestion; acts as substrate for gut microbial metabolism affecting systemic lipid levels.
• Reproductive/Lactation: Present in human milk; proposed role in preventing plugged ducts in breastfeeding.
• Cellular membranes (all tissues): Lecithin is required for proper biological function and is a common compound found in cells of all living organisms.

6. Dosage Forms and Doses Reported in Studies

Lecithin is commercially available in multiple forms for supplemental use:

• Granules (de-oiled): Typically added to food or beverages.
• Softgel capsules: A common dietary supplement form.
• Liquid/oil form: Used as a food additive and supplement.
• Powder: Refined lecithins with high levels of phospholipids (greater than 95%), prepared by acetone and alcohol fractionation, are soft, yellow-brown powders.

Doses reported in clinical and research contexts:

• Nine patients with type IIa and type IV hyperlipoproteinemia were given soya lecithin 12 g/day for 3 months in one published human study.
• Seventeen hypertriglyceridemic patients subsequently received increasing doses of soya lecithin for 1-month periods: 6, 12, and 18 g/day.
• One soy lecithin capsule (500 mg) was administered daily in the Mourad et al. (2010) hypercholesterolemia study.
• In 1943, Adlersberg and Sobotka reported administering 12–15 grams daily of unrefined soy lecithin in the diet for 2–3 months in five human patients.
• Lecithin has been described as being orally administered in amounts of between about 0.1 and 100 g/day in one patent reference noting therapeutic applications.

7. Safety Considerations and Interactions

7.1 Regulatory Safety Assessment

The EFSA ANS Panel concluded that there was no need for a numerical Acceptable Daily Intake (ADI) for lecithins (E 322) and that there was no safety concern for the general population from more than 1 year of age at the refined exposure assessment for the reported uses of lecithins (E 322) as a food additive. The Panel further concluded that there is no safety concern for the exposure to choline from lecithins (E 322) as a food additive at use and use levels reported by industry. Similarly, the UN Joint FAO/WHO Expert Committee on Food Additives (JECFA) had previously designated an ADI of "not limited" for lecithin, indicating a high margin of safety at food-use levels.

7.2 Gastrointestinal Effects

Oral phosphatidylcholine has generally not been associated with serious adverse events, though some minor events have been reported including excessive sweating and gastrointestinal events. Safety data in clinical studies using essential phospholipids is poorly reported, but the most commonly reported adverse events are mild gastrointestinal events.

7.3 Soy Allergy and Allergenicity

Soy lecithin does not contain enough allergenic proteins for most people allergic to soy, although the US FDA only exempts a few soy lecithin products from its mandatory requirements for allergenic source labeling. In 2014, the EFSA Panel on Dietetic Products, Nutrition, and Allergies prepared a scientific opinion on the evaluation of allergenic foods and food ingredients for labelling purposes where the allergenicity of egg and soya lecithins were considered. The lowest minimum eliciting dose (MED) reported in soya-allergic patients undergoing double-blind placebo-controlled food challenge was 0.2 mg of soya protein, although the majority of patients only reacted to higher doses.

Drug products containing soy lecithin can cause severe allergic reactions in patients allergic to peanuts or soy. Lecithin contaminated by soy proteins and used as an excipient in drugs can cause reactions in patients with soy allergy. For that reason, the source of lecithin should always be specified among the constituents of drugs to avoid a source of hidden allergens.

An alternative source of lecithin, derived from sunflowers, is available as a dietary supplement for those with concerns about soy-based foods. The sunflower-derived form does not carry the same soy allergen risk.

7.4 TMAO and Cardiovascular Risk Signal

The primary concern with choline supplementation in general has been elevations in the pro-inflammatory gut-derived metabolite TMAO. Soy lecithin contains choline, and choline may raise blood levels of a certain compound (TMAO) that has been linked with adverse health effects. This concern applies specifically to individuals with certain gut microbiota compositions that efficiently convert dietary choline to trimethylamine, which is then oxidized to TMAO in the liver. The magnitude of this risk from supplemental lecithin use, as opposed to high dietary choline intake overall, has not been resolved in human clinical trials.

7.5 Egg Lecithin Allergenicity

The possibility of residual allergenicity in food products manufactured using egg lecithin has been reported in a double-blind placebo-controlled food challenge. Heat denaturation and other food-processing treatments do not reliably reduce the allergenicity of egg. Minimum eliciting doses of ingested egg proteins reported to trigger objective reactions in clinical studies range from a few micrograms to milligrams.

7.6 EFSA Concerns Regarding Neurodevelopmental Effects at High Doses

The main safety issue identified in the EFSA ANS Opinion concerned indications that the development of the brain was altered at concentrations in the diet of 5% soya lecithins and higher during gestation, lactation, and the post-weaning period observed in toxicity studies. However, it has to be noted that these studies had limitations which precluded firm conclusions by the ANS Panel.

7.7 EU Labeling Requirements

Soybeans and eggs and products thereof, including lecithins, are listed in Annex II of EU Regulation 1169/2011 as substances or products causing allergies or intolerances, for which indication as allergens is mandatory food information.

References

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