Great, I’ll gather data on how mead acid supplementation affects fatty acid composition in humans and human-substitute animals, focusing especially on adipose and plasma tissues, but including others where relevant. I’ll include both clinical and preclinical studies across all dosages and durations.I’ll get started and let you know when the results are ready.

Effects of Mead Acid (20:3 n−9) Supplementation on Fatty Acid Profiles

Introduction

Mead acid (5,8,11-eicosatrienoic acid; 20:3 n–9) is an ω-9 polyunsaturated fatty acid historically identified in animals deprived of essential fatty acids (EFAs)pmc.ncbi.nlm.nih.gov. In EFA deficiency, the body converts oleic acid (18:1 n–9) into mead acid via desaturation and elongation, as a compensatory response to low ω-6/ω-3 availabilitypmc.ncbi.nlm.nih.gov. Under normal diets, mead acid is only a trace fatty acid in tissues, whereas it accumulates substantially when dietary linoleic acid (LA, 18:2 n–6) and α-linolenic acid (ALA, 18:3 n–3) are insufficient. In fact, an elevated ratio of 20:3 n–9 (triene) to 20:4 n–6 (tetraene) in blood lipids (Holman’s “triene/tetraene” index) is a classic biomarker of EFA deficiencypmc.ncbi.nlm.nih.gov. Beyond deficiency states, there is growing interest in mead acid supplementation – i.e. providing 20:3 n–9 exogenously – to investigate its incorporation into tissues and its interactions with essential fatty acid metabolism. This report reviews findings from both clinical observations and preclinical studies (rodents, pigs, and cell models) on how mead acid supplementation alters fatty acid composition in plasma, adipose tissue, and other organs. We highlight changes in major fatty acid classes (saturated, monounsaturated, ω-6, and ω-3) upon mead acid intake, and discuss mechanistic insights into how the presence of mead acid affects EFA pathways.

Plasma Fatty Acid Profile Changes with Mead Acid Supplementation

Human data: In healthy EFA-sufficient humans, mead acid typically constitutes only a very minor fraction of plasma fatty acids (often <0.1–0.3%). When EFA intake is curtailed, however, plasma mead acid rises markedly. Classic studies of human linoleic acid deficiency in the 1960s–70s showed that patients on fat-free or low-EFA diets developed measurable 20:3 n–9 in plasma lipids concurrent with drops in ω-6 levelspmc.ncbi.nlm.nih.gov. For example, Collins et al. (1971) reported that EFA-deficient patients’ plasma cholesteryl esters showed an abnormal 20:3 n–9 peakpmc.ncbi.nlm.nih.gov. In modern contexts, cystic fibrosis (CF) patients (who often exhibit an “EFA deficiency-like” plasma profile) have elevated mead acid in serum alongside reduced LA, arachidonic acid (AA, 20:4 n–6), and docosahexaenoic acid (DHA, 22:6 n–3) levelspmc.ncbi.nlm.nih.gov. Notably, the fatty acid pattern in CF is somewhat atypical: mead acid is high and EFAs are lower than normal, but not as extremely depleted as in outright dietary deficiencypmc.ncbi.nlm.nih.gov. These human observations reinforce that increased mead acid in plasma inversely correlates with essential PUFA status. Direct supplementation of mead acid in humans is not well documented in the literature; however, parenteral nutrition studies offer indirect evidence. In patients recovering from gastrointestinal surgery, use of lipid emulsions high in oleic acid (and low in LA) led to gradual rises in plasma 20:3 n–9, unless sufficient LA was providedwww.sciencedirect.com. Together, clinical evidence suggests that raising mead acid availability (by diet or endogenous synthesis) pushes the plasma fatty acid profile toward an “EFA-deficient” pattern – i.e. higher relative ω-9 triene content and lower ω-6 and ω-3 proportions.Rodent studies: Controlled feeding experiments in rats and mice have provided detailed data on plasma fatty acid changes with mead acid-enriched diets. Cleland et al. (1996) fed young rats diets containing up to ~19% mead acid by weight of fat (using a fungal oil rich in 20:3 n–9, “Mut 48” oil) for 4 weekslink.springer.comlink.springer.com. Plasma total lipids in these rats showed dramatic incorporation of the supplemented mead acid: in plasma phospholipids, cholesteryl esters, and triglycerides, mead acid rose from essentially 0 to as high as ~20% of total fatty acidslink.springer.com. This is a striking increase, given that mead acid is normally almost undetectable in well-fed animals. The degree of 20:3 n–9 accumulation depended on dietary EFA context – notably, when dietary LA was high (∼19% of fatty acids), tissue incorporation of mead acid was significantly lower than when LA was lowlink.springer.com. In other words, abundant ω-6 intake “crowded out” some of the mead acid incorporation. By contrast, low-LA diets enabled mead acid to replace a larger fraction of membrane fatty acidslink.springer.com. This competitive effect illustrates how mead acid and LA/AA vie for positions in plasma and tissue lipids.A representative outcome from rodent supplementation is shown in Table 1. For instance, James et al. (1993) supplemented rats with 20:3 n–9 (in an otherwise EFA-sufficient diet) and observed that neutrophil phospholipids incorporated mead acid at ~7–10% of total fatty acids (versus ~0% in controls)pmc.ncbi.nlm.nih.gov. In parallel, plasma mead acid levels would be elevated (though that study focused on leukocytes). More recently, Emoto et al. (2015) fed rats a diet with 2.4% of total fat as mead acid and reported plasma (serum) 20:3 n–9 rising to ≈39% of total fatty acids, compared to ~4% on the control dietpmc.ncbi.nlm.nih.gov. In that experiment, absolute serum mead acid increased nearly 6-fold (to ~731 μg/mL) and became the second most abundant PUFA after AA. Despite this huge enrichment of ω-9 in plasma, the major ω-6 and ω-3 PUFA levels in serum did not drop proportionately in the short term; as a result the ratio of mead acid to DHA climbed ~13-fold (0.04 to 0.50) and mead/AA ratio ~14-fold (0.4% to 5.6%)pmc.ncbi.nlm.nih.govpmc.ncbi.nlm.nih.gov. These data suggest that with adequate essential fatty acid present, plasma AA and DHA are maintained in absolute amount, but mead acid simply adds to the pool (diluting the relative percentage of other FAs). On the other hand, under borderline EFA intake conditions, mead acid can partly replace missing ω-6s in plasma. For example, a pig study (Duranthon et al. 1991) found that after 12 weeks on an EFA-deficient diet, plasma membrane phospholipids had “largely reduced” LA content while mead acid (and oleic acid) filled in to maintain total unsaturation indexlink.springer.com. Notably, those EFA-deficient pigs kept their AA levels relatively stable by drawing on tissue stores, but still accumulated some 20:3 n–9link.springer.com.Table 1. Selected Examples of Plasma Fatty Acid Changes with Mead Acid (20:3 n–9) Supplementation

Adipose Tissue Fatty Acid Composition Changes

Adipose tissue is a long-term fat storage compartment, and its fatty acid profile shifts more gradually in response to diet. There are fewer direct studies measuring adipose composition after mead acid supplementation, but available evidence and analogies from EFA deficiency suggest notable changes in adipose fatty acid makeup when 20:3 n–9 is abundant.In healthy humans, adipose tissue triglycerides typically contain ~10–15% linoleic acid (reflecting the habitual diet)aspenjournals.onlinelibrary.wiley.com and virtually no mead acid. During prolonged EFA deficiency, however, adipose stores become depleted of linoleate as it is mobilized to vital organsaspenjournals.onlinelibrary.wiley.com. The body may eventually deposit some mead acid into adipose TG as it accumulates in the plasma. In early rat studies on fat-free diets, mead acid was indeed detected in adipose depots of deficient animals, whereas control rats had nonepmc.ncbi.nlm.nih.gov. Mead and coworkers (1950s) noted that adipose and skin lipids of fat-deficient rats contained unusual trienoic acid (20:3 n–9) in place of polyunsaturatespmc.ncbi.nlm.nih.gov. Thus, under EFA deprivation the adipose tissue gradually adopts a “Mead acid signature” – higher oleic and 20:3 n–9 content – although this may take many weeks or months.When mead acid is provided exogenously in the diet, adipose tissue is expected to incorporate it similarly to other dietary fats. In rodent supplementation experiments of 4–8 weeks, significant 20:3 n–9 accumulation has been documented in liver, spleen, and blood, but adipose tissue was not always analyzed. Nonetheless, it is reasonable to extrapolate that dietary mead acid entering circulating lipoproteins will ultimately be deposited in adipose stores. For example, if plasma triglycerides reach ~20% mead acidlink.springer.com, the adipose TG formed from those lipoproteins should reflect a comparable composition over time. In a mouse study by Watanabe et al. (2001), feeding a mead acid-rich diet for 8 weeks led to significant 20:3 n–9 incorporation in peritoneal cells and presumably in fat depots, as the authors noted mead acid was taken up “in proportion to the amount present in the diet” across tissueslink.springer.com. Although quantitative adipose data were not given, one can infer that adipose tissue would accumulate mead acid up to several percent of total fatty acids with sustained intake.One illuminating case comes from a pig model: pigs on a 12-week EFA-deficient regimen (high oleate, minimal linoleate) showed marked shifts in adipose and membrane lipids. Their adipose tissue (and other organs) maintained overall unsaturation by increasing 18:1 n–9 and 20:3 n–9, effectively replacing the lost polyunsaturateslink.springer.com. In these pigs, adipose LA fell from normal levels to near-zero, while mead acid became detectable in adipose lipids (precise values not reported, but the trend was clear)link.springer.com. Similarly, rats fed hydrogenated coconut oil (rich in saturates, no EFAs) for an extended period showed emergence of mead acid in depot fat, indicating the body was actively storing the ω-9 polyunsaturate synthesized in response to deficiencyjn.nutrition.orgwww.jlr.org.In summary, adipose tissue mirrors the plasma changes over longer timescales. With mead acid supplementation, adipose fat gradually becomes enriched in 20:3 n–9 and relatively poorer in essential fatty acids. If the diet still contains some LA/ALA, adipose will retain a portion of those EFAs (acting as a buffer), but the relative balance shifts. Saturated fat content in adipose is mostly dictated by diet and de novo lipogenesis, and is not directly altered by mead acid aside from dilution effects. Monounsaturated fat (oleate) in adipose may increase concomitantly with mead acid under EFA-poor conditions (since oleate is the precursor and often co-varies), whereas in an EFA-adequate but mead-supplemented scenario, oleate’s share might remain stable or even decrease slightly if dietary oleic is partly replaced by mead acid. Overall, the presence of high mead acid in adipose indicates a shift toward an EFA-deficient fat profile: lower linoleic and arachidonic acid percentages, compensated by higher oleic and mead acid content. This altered adipose composition could have functional implications, for example in adipose signaling or release of fatty acids during fasting, though such effects are beyond the scope of this review.

Other Tissues (Liver, Brain, Muscle) and Compartments

Different tissues incorporate mead acid to varying extents depending on their specific fatty acid uptake and turnover. Liver readily reflects dietary fatty acid composition. In mead acid–fed rodents, liver phospholipids can accumulate substantial 20:3 n–9. Cleland et al. observed up to ~15% of total fatty acids as mead acid in liver phospholipids of rats on the high-20:3 n–9 dietlink.springer.com. The spleen showed similar levels (≤15% in PL)link.springer.com. Such high incorporation in liver indicates that mead acid becomes a notable component of hepatocyte membranes and lipid stores when available. Despite this, the liver remained histologically normal in those ratslink.springer.com, suggesting no overt toxicity from replacing a portion of membrane PUFAs with 20:3 n–9 over the short term.Immune cells and blood cell membranes also take up mead acid. Peritoneal leukocytes in rats reached ~11% mead acid in their total lipids on the enriched dietlink.springer.com. Mouse peritoneal exudate cells similarly incorporated mead acid proportional to intakelink.springer.com, with up to ~10 mol% in cell phospholipids in one studyjn.nutrition.orgjn.nutrition.org. Notably, human platelets can incorporate mead acid into their membranes when exposed; experiments have shown that platelet phospholipids will integrate 20:3 n–9 and this can modulate their function (platelet reactivity increased modestly in the presence of mead acid)pmc.ncbi.nlm.nih.govpmc.ncbi.nlm.nih.gov. Endothelial cells in culture likewise incorporate mead acid into their lipidspmc.ncbi.nlm.nih.gov. These findings demonstrate that most cell types can incorporate mead acid into membrane phospholipids if it is available in circulation, often at the expense of arachidonic acid content.Brain and nervous tissue are more protected and slower to change fatty acid composition. The blood–brain barrier and specific fatty acid transporters prioritize essential ω-3 and ω-6 PUFAs for incorporation into neural membranes. As a result, brain and retinal tissues show only limited uptake of dietary mead acid. In the rat study with 2.4% dietary mead acid, the retina’s fatty acids changed minimally: retinal 20:3 n–9 rose from 0.37% to 2.61% of total fats (a small absolute increase)pmc.ncbi.nlm.nih.gov, whereas serum showed a far larger jump to ~39%pmc.ncbi.nlm.nih.gov. The lens of the eye likewise increased mead acid only from ~0.9% to 2.0%pmc.ncbi.nlm.nih.gov. This indicates that while ocular tissues did take up some mead acid, the magnitude was “not remarkable” compared to serumpmc.ncbi.nlm.nih.gov. Extrapolating to the brain, one would expect minor incorporation of mead acid into the brain’s lipids unless EFAs are severely deficient for a long period. Indeed, in severe EFA deficiency, the brain’s AA and DHA levels can drop and be partially replaced by docosatrienoic acids (the elongation products of mead acid or other ω-9 PUFA). But in short-term supplementation with concurrent normal EFAs, the brain likely keeps its fatty acid profile largely intact, with mead acid remaining a very small component. This conservative incorporation is consistent with the critical structural role of AA and DHA in neural tissues – the brain will resist swapping them out for an “inferior” substitute. One supporting observation: reelin-deficient mice (a model with metabolic quirks) were found to have high mead acid in cortical phospholipidspmc.ncbi.nlm.nih.gov, hinting that only when normal fatty acid homeostasis is disrupted will the brain accumulate mead acid in notable amounts.Muscle tissue falls somewhere in between – skeletal muscle membranes can incorporate dietary fatty acids, but there is limited direct data on mead acid in muscle. It is likely that muscle phospholipids follow a pattern similar to other peripheral tissues (i.e., moderate 20:3 n–9 incorporation if fed). For instance, if liver and immune cells reach ~10% mead acid, muscle might incorporate a few percent into its phospholipids under the same diet. Since muscle typically has a high proportion of oleate and palmitate in its lipids, added mead acid would primarily replace some LA/AA in membrane phospholipids. Without explicit studies, one can only extrapolate; however, no unique resistance of muscle to mead acid has been noted, so it should reflect the systemic fatty acid changes to a reasonable degree.In summary, most tissues incorporate mead acid according to availability, but critical organs like the brain and retina limit its uptake. Liver, adipose, immune, and epithelial tissues can attain high levels of 20:3 n–9 when it is abundant, altering their PUFA composition significantly. Meanwhile, the central nervous system retains a preference for essential fatty acids, resulting in only minimal mead acid in those tissues unless EFAs are nearly absent.

Interactions with Essential Fatty Acid Metabolism and Mechanistic Insights

Mead acid’s presence has important metabolic and functional interactions with the essential fatty acid pathways. Several mechanisms explain how 20:3 n–9 substitution influences fatty acid metabolism:

• Competition for Incorporation: Mead acid competes with ω-6 and ω-3 fatty acids for incorporation into cell membranes and lipid fractions. As shown in rat studies, a higher dietary LA content suppresses mead acid accumulation in tissueslink.springer.com. Essentially, when both LA (or AA) and mead acid are present, cells preferentially incorporate the essential ω-6, relegating mead acid to a lesser share. Conversely, if ω-6 intake is low, mead acid readily occupies those “slots” in triglycerides and phospholipidslink.springer.com. This competition extends to enzymatic processes: the same elongases and desaturases that produce AA from LA will produce mead acid from oleate if LA is unavailable. In fact, feeding a high-oleate, low-LA diet can induce a mild EFA deficiency precisely because oleate and its product mead acid outcompete the scarce linoleate for desaturation pathwaysjn.nutrition.orgwww.jlr.org. The net result is an altered balance where mead acid partially replaces what would have been AA or other long-chain PUFA in cell lipids.
• Altered Eicosanoid Production: One of the most studied mechanistic effects of mead acid is its impact on eicosanoid synthesis. Mead acid (20:3 n–9) is an analog of AA (20:4 n–6) and dihomo-γ-linolenic acid (20:3 n–6, DGLA), and it can be acted upon by cyclooxygenase (COX) and lipoxygenase (LOX) enzymes. However, the eicosanoids derived from mead acid are atypical and generally less potent than those from AA. Importantly, mead acid inhibits certain AA-derived eicosanoids. James et al. (1993) demonstrated that rats supplemented with 20:3 n–9 had neutrophils with significantly lower leukotriene B₄ (LTB₄) synthesis upon stimulationpmc.ncbi.nlm.nih.gov. LTB₄ (a pro-inflammatory 5-LOX product of AA) dropped, even though other 5-LOX products like 5-HETE were not suppressedpmc.ncbi.nlm.nih.gov. The mechanism was pinpointed to mead acid (or a mead acid–derived metabolite) inhibiting leukotriene A₄ hydrolase, the enzyme that converts LTA₄ to LTB₄pmc.ncbi.nlm.nih.gov. In essence, high mead acid in neutrophil membranes leads to a biochemical block that reduces LTB₄ output. Supporting this, neutrophils from EFA-deficient humans (who have elevated 20:3 n–9) similarly showed impaired LTB₄ productionpmc.ncbi.nlm.nih.gov. Notably, an in vitro study found mead acid to be a more potent inhibitor of LTB₄ formation than even eicosapentaenoic acid (EPA, 20:5 n–3)pmc.ncbi.nlm.nih.gov. This selective suppression of 5-LOX/LTA hydrolase products suggests a functional antagonism where mead acid presence can make inflammatory responses milder (since LTB₄ is a strong neutrophil chemotactic agent). On the COX side, mead acid may yield 1-series prostaglandins (similar to DGLA’s metabolism), but evidence is mixed on how it affects AA-derived prostaglandins. In mice, a mead-rich diet did not significantly reduce PGE₂ or thromboxane levels in vivopmc.ncbi.nlm.nih.gov, indicating COX pathways remained largely intact. Yet, another study noted that macrophage-like cells accumulating mead acid in culture showed decreased production of several prostaglandins and thromboxanespmc.ncbi.nlm.nih.gov. It is possible that mead acid competes as a substrate, producing some less-inflammatory prostanoids (e.g. PGE₁ analogs) and in doing so slightly lowers the yield from AA. Overall, mead acid tilts the eicosanoid profile toward a less inflammatory state: LTB₄ and cysteinyl-leukotrienes are curtailedpmc.ncbi.nlm.nih.gov, while prostaglandin synthesis is either unaltered or only mildly affected. This is somewhat analogous to the effects of ω-3 EPA supplementation (which also reduces LTB₄ and yields weaker 5-series leukotrienes)pmc.ncbi.nlm.nih.govjn.nutrition.org. Indeed, researchers have noted that dietary mead acid mimics some anti-inflammatory effects of fish oil, making it of interest for conditions like arthritisjn.nutrition.org.
• Signaling and Gene Regulation: Beyond serving as a structural lipid or eicosanoid precursor, mead acid may influence cell signaling pathways. For example, in skin inflammation models, mead acid showed an ability to activate peroxisome proliferator-activated receptor alpha (PPARα). Intraperitoneal injection of mead acid in mice suppressed neutrophil migration in a skin hypersensitivity reaction and blocked p38 MAP kinase activation in keratinocytes, ultimately reducing keratinocyte hyper-proliferation and inflammatory chemokine expressionpmc.ncbi.nlm.nih.gov. These effects were attributed to PPARα activation (a known anti-inflammatory route)pmc.ncbi.nlm.nih.gov. Thus, mead acid might act as a modulatory ligand for lipid-sensing nuclear receptors. Additionally, high cellular mead acid could alter membrane microdomain properties (since it is slightly less polyunsaturated than AA, it may affect membrane fluidity and raft formation). One study on salivary gland membranes in rats noted that EFA deficiency (with elevated oleate and mead acid) led to lower membrane fluidity and coincided with higher basal adenylate cyclase activityjn.nutrition.orgjn.nutrition.org, hinting that replacing AA with mead acid in membranes can have downstream effects on membrane enzymes and receptors.
• Inability to Fully Substitute for EFAs: Mechanistic insight also comes from what mead acid cannot do. Despite its integration into many lipid pools, mead acid cannot fulfill all the roles of true essential fatty acids. For instance, animals fed only mead acid (but no ω-6) still develop classic deficiency symptoms (poor growth, scaly dermatitis, organ dysfunction). A study in rodents showed that mead acid supplementation failed to prevent retinal degeneration induced by a carcinogen, whereas diets with ω-6 would normally help tissue repairpmc.ncbi.nlm.nih.gov. Similarly, topical application of mead acid to EFA-deficient mouse skin did not resolve the dermal symptoms – in fact, earlier reports even accused mead acid of causing the dermatitis, though later it was understood that oleic acid buildup in skin ceramides is the main issuepmc.ncbi.nlm.nih.gov. The takeaway is that mead acid cannot replace LA in structural lipids like acyl-ceramides or in supporting normal growth, confirming that ω-6 and ω-3 PUFA have unique biological roles beyond maintaining membrane fluidity. This is why mead acid is considered a marker of deficiency rather than a cure for it. Even so, mead acid’s presence can ameliorate some biochemical aspects (e.g. preserving an adequate unsaturation index in tissueslink.springer.com and dampening hyperinflammatory signaling), but it is not truly “essential.”

Conclusion

In summary, dietary mead acid (20:3 n–9) supplementation profoundly alters fatty acid profiles in vivo, especially in plasma and readily exchangeable lipid pools. In both humans and animal models, elevated mead acid is associated with reduced proportions of essential ω-6 and ω-3 fatty acids in tissues – essentially recapitulating features of essential fatty acid insufficiency. Plasma and most organs can incorporate mead acid to high levels when provided, whereas the brain and other highly specialized tissues limit its uptake. Adipose tissue, as a long-term reservoir, will slowly mirror dietary intake by storing mead acid at the expense of linoleate/arachidonate content if the latter are not adequately supplied. Mechanistically, the presence of mead acid interacts with EFA metabolism by competing for membrane space and enzymatic pathways, resulting in modified eicosanoid profiles (e.g. less LTB₄) and altered cell signaling in some contexts. These changes suggest potential anti-inflammatory benefits of mead acid enrichment – a concept borne out in animal studies showing attenuation of inflammatory responsespmc.ncbi.nlm.nih.govpmc.ncbi.nlm.nih.gov. However, mead acid cannot completely replace the essential biochemical functions of ω-6/ω-3 fatty acids, and an over-reliance on 20:3 n–9 ultimately reflects a deficient state.In conclusion, mead acid supplementation leads to a distinctive fatty acid profile characterized by high ω-9 mead acid content, lower relative ω-6/ω-3 levels, and compensatory increases in oleic acid, particularly in plasma, adipose, and hepatic tissues. This altered profile can modulate physiological processes – dampening certain inflammatory mediators – yet underscores the delicate balance in fatty acid metabolism. The literature to date, spanning cell culture to clinical observations, paints mead acid as a double-edged sword: a useful stand-in to maintain membrane fluidity and curb inflammation when EFAs are lacking, but also a stark indicator of when essential fats are out of balance. Further research is warranted to explore therapeutic angles of mead acid (for example, as an anti-inflammatory lipid supplement) while carefully monitoring its impact on overall fatty acid homeostasislink.springer.comjn.nutrition.org.