Pinolenic acid

Pinolenic Acid: A Comprehensive Reference

1. Identity and Chemical Characterization

1.1 Chemical Names and Classification

Pinolenic acid is a polyunsaturated fatty acid (PUFA) primarily found in the oils of Siberian and Korean pine nuts, as well as other species of the genus Pinus. It is chemically designated as all-cis-5,9,12-octadecatrienoic acid, with the molecular formula C₁₈H₃₀O₂. In systematic lipid nomenclature, pinolenic acid is formally designated as all-cis-5,9,12-18:3. Its CAS registry number is 16833-54-8.

Some sources also use the term columbinic acid for this substance, though columbinic acid sometimes designates an E-Z isomer (trans,cis,cis delta-5,9,12/18:3) in the biological literature. Pinolenic acid is an isomer of gamma-linolenic acid (GLA). While GLA is an ω-6 essential fatty acid (EFA), pinolenic acid is not.

The compound is characterized by three double bonds located at the 5th, 9th, and 12th positions of the carbon chain, all in the cis configuration. This non-methylene-interrupted arrangement—where adjacent double bonds are separated by more than one methylene group—is what distinguishes pinolenic acid structurally from most other dietary PUFAs. Pine nut oil (PNO) is rich in a variety of unusual delta-5-non-methylene-interrupted fatty acids (NMIFAs); these include pinolenic acid (PLA; all cis-5,-9,-12 18:3), sciadonic acid (all cis-5,-11,-14 20:3), and taxoleic acid (all cis-5,-9 18:2). PLA is the most abundant of these NMIFAs in PNO, comprising 14–19% of the total fatty acids present in most pine nut oils.

Pinolenic acid, or 5,9,12-18:3, is synthesized in gymnosperms by the action of a Δ5 desaturase on linoleate. PLA has been reported to be produced from linoleic acid (LA; all cis-9,-12 18:2) by a species-specific delta-5 desaturase.

1.2 Botanical Sources and Natural Occurrence

Pine nuts come from the Pinus genus, and 29 species have been listed as having edible nuts by the Food and Agriculture Organization of the United Nations (FAO). Pine nuts derived from Pinus koraiensis (Korean pine), Pinus sibirica (Siberian pine), Pinus pinea (stone pine), and Pinus gerardiana (chilgoza pine) are most commonly consumed by humans.

Pinolenic acid is contained in Siberian pine nuts, Korean pine nuts and the seeds and xylem of other pine (Pinus) species. The highest percentage of pinolenic acid is found in Siberian pine nuts and the oil produced from them. Quantitatively, the richest source of PNLA is the oil pressed from Siberian pine nuts, which contains up to 27% of this PUFA. Gas chromatography of Pinus koraiensis nut oil has shown that the predominant fatty acid is linoleic acid (45.36%–45.91%), followed by oleic acid (26.91%–27.10%), and pinolenic acid (13.33%–13.63%).

Across the Pinus genus more broadly, PNLA and sciadonic acids occur in all analyzed pine taxa, while taxoleic and bishomopinolenic acids were present in most; PNLA reached a maximum of 28.3% of total fatty acids in P. mugo, and P. koraiensis showed the highest total fatty acid amount (66.8 g/100 g seeds).

Siberian pines (growing in Russia, Mongolia and Kazakhstan), as well as Korean pines yield the seeds with the highest content of pinolenic acid, as well as antioxidants associated with medicinal uses. China, North Korea, Russia (Siberia), Pakistan, and Afghanistan are the largest exporters of pine nuts and pine nut oil, while Korea, the USA, and Russia are the largest consumers.

1.3 Common Forms and Preparations

Pinolenic acid is commercially available and studied primarily as a constituent of pine nut oil (PNO), which is obtained by several methods. Green extraction methods such as supercritical fluid extraction, ultrasound and/or microwave-assisted extraction, pulsed electric field-assisted extraction, pressurized liquid extraction, enzymatic hydrolysis, and mechanical expression (cold pressing) are commonly used for oil extraction from pine nuts. Cold pressing has gained attention in recent years due to the pure and high-quality products that can be obtained via this process. Oil yield depends upon the mode of extraction (e.g., cold pressing, solvent extraction), but is typically reported to be 45 to 65 g/100 g of nut.

Pine nut oil has a relatively low smoke point, and is therefore not generally used during cooking; rather, it is added to foods for "finishing," to add flavor. As a dietary supplement, pine nut oil is sold in gel capsule and liquid forms. One commercially studied preparation, PinnoThin™, is a pine nut oil concentrate derived from Korean pine (Pinus koraiensis) that was used in several clinical trials.

For research and concentrated supplementation purposes, pinolenic acid can be selectively concentrated through solvent fractionation, using solvents like n-hexane at low temperatures; this technique can yield high concentrations of pinolenic acid (up to 69.8 wt%) with good efficiency. Enzymatic reactions using lipase-catalyzed processes are also employed to selectively concentrate pinolenic acid from crude oils. Additionally, the positional distribution pattern of fatty acids in triacylglycerols (TAGs) affects intestinal absorption; structured pinolenic TAGs (SPT), in which PLA is evenly distributed on the glycerol backbone, differ from natural pine nut oil where PLA is predominantly positioned at the sn-3 position. SPT can be prepared via nonspecific lipase-catalyzed esterification of glycerol with free fatty acids obtained from PNO.

2. Traditional and Historical Use

Korean pine nuts are rich in oils and have been used around the world for centuries for culinary purposes. They are one of the main types of commercial pine nuts available in the world today. The seeds are edible and the oil extracted from them has nutritional and medicinal properties. In China, the seeds are considered to have a tonic effect, as well as to help with digestion (stomachic action).

Pine nuts have long been constituent parts of the diets of many cultures, particularly in the Mediterranean and Asian regions, and they are now also consumed very widely outside these geographical areas. Pine nuts are both eaten raw and used in cooking in various parts of the world.

Pinolenic acid, a polyunsaturated fatty acid primarily found in the seeds of pine trees such as Pinus koraiensis and Siberian pine, has a long history of use in traditional medicine, especially in East Asia and Russia. For centuries, pine nuts and their oil have been consumed for their nourishing properties and were highly valued in folk remedies aimed at supporting healthy digestion, boosting vitality, and alleviating inflammation.

It is important to note that traditional preparations used the whole pine nut or cold-pressed pine nut oil, not isolated pinolenic acid, as the isolation of individual fatty acids is a modern technological achievement. Thus, historical references pertain to the use of pine nuts and pine nut oil rather than purified pinolenic acid. The identification of pinolenic acid as a key bioactive component in these oils is a development of modern analytical chemistry.

3. Key Constituents and Mechanisms of Action

3.1 Structural Distinction: Non-Methylene-Interrupted Fatty Acid

The primary mechanism underlying pinolenic acid's distinct biological profile is its unusual chemical structure. The oil is rich in fatty acids including Δ5-unsaturated polymethylene-interrupted fatty acids (Δ5-UPIFAs), which are characteristic of the seeds of gymnosperms and differ from the structure of other polyunsaturated fatty acids (PUFAs). The consequence of this non-methylene-interrupted arrangement is that pinolenic acid interacts differently with the enzymatic systems of mammalian metabolism than standard ω-6 or ω-3 fatty acids.

3.2 Metabolic Fate: Conversion to Eicosatrienoic Acid (ETA)

Pine nut oil is rich in a variety of unusual delta-5-non-methylene-interrupted fatty acids (NMIFAs), including pinolenic acid (PLA; all cis-5,-9,-12 18:3), which typically comprises 14 to 19% of total fatty acids. PLA has been shown to be metabolized to eicosatrienoic acid (ETA; all cis-7,-11,-14 20:3) in various cells and tissues. The metabolism of PNLA in mammalian systems is not well explored; however, in rat liver microsomes and human hepatoma HepG2 cells, PNLA was elongated by the fatty acid chain elongation system to Δ-7 eicosatrienoic acid (Δ-7 ETA; all cis-7,-11,-14-20:3). The few studies which have examined effects of ETA indicate it has anti-inflammatory properties.

Importantly, pinolenic acid is not converted to arachidonic acid metabolically and can reduce arachidonic acid levels in the phosphatidylinositol fraction of HepG2 cells from 15.9% to 7.0%. This capacity to displace arachidonic acid—the principal precursor of pro-inflammatory eicosanoids—may be central to pinolenic acid's anti-inflammatory effects.

3.3 Free Fatty Acid Receptor Agonism (FFA1/FFA4)

One of the most significant mechanistic discoveries regarding pinolenic acid was the identification of its receptor targets. The medium- and long-chain NEFA receptor FFA1 (free fatty acid receptor 1, previously known as GPR40) has been linked to enhancement of glucose-stimulated insulin secretion, whereas FFA4 (free fatty acid receptor 4, previously known as GPR120) has been associated with insulin-sensitizing and anti-inflammatory effects, and both receptors are reported to protect pancreatic islets and promote secretion of appetite and glucose-regulating hormones. Of the screened compounds, pinolenic acid, a constituent of pine nut oil, was identified as a relatively potent and efficacious dual FFA1/FFA4 agonist, and its suitability for further studies was confirmed by additional in vitro characterization.

3.4 Suppression of Pro-Inflammatory Cytokines and Eicosanoids

Like essential fatty acids, pinolenic acid forms biologically active metabolites in the presence of cyclooxygenase or lipoxygenase. In cell-based studies, pinolenic acid has been shown to reduce the production of pro-inflammatory mediators. Uptake and incorporation of pinolenic acid into macrophage phospholipids reduces n-6 polyunsaturated fatty acid levels and downstream prostaglandin formation. IL-6, TNF-α, and prostaglandin E2 (PGE2) release by lipopolysaccharide (LPS)-stimulated PBMCs from RA patients and healthy controls was measurably reduced by PNLA.

3.5 Antioxidant Mechanisms (Nrf2/Keap1 Pathway)

In vitro research has elucidated an antioxidant mechanism for pinolenic acid. Under supplementation with PNA, the activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) was improved. Further studies on gene expression showed that under the regulation of PNA, the expression level of the Keap1 gene was decreased while the Nrf2 gene was increased. The expression levels of HO-1 and NQO1 downstream of Nrf2 were increased. Results indicated that, under the regulation of PNA, Nrf2 was separated from Keap1, entered the nucleus, bound to ARE, and up-regulated the expression levels of HO-1 and NQO1 genes. These findings are from in vitro cell culture experiments and their relevance to human physiology requires further investigation.

3.6 LDL Receptor Upregulation

Pinolenic acid may have LDL-lowering properties by enhancing hepatic LDL uptake. Cell-culture studies (notably using HepG2 hepatoma cells enriched with pinolenic acid by crystallization of Korean pine nut oil) have indicated upregulation of hepatic LDL receptor activity. This represents a potential mechanism for the lipid-lowering effects observed in animal and some human studies.

3.7 Satiety Hormone Stimulation

Dietary fat in the gastrointestinal tract triggers the release of the satiety gut hormones cholecystokinin (CCK) in the proximal small intestine (duodenum), and glucagon-like peptide-1 (GLP-1) in the distal small intestine (ileum). Pinolenic acid appears to stimulate this release more potently than many other dietary fatty acids, acting at least in part through the FFA1 and FFA4 receptor pathway described above. In vitro studies on Korean pine nut fatty acids have shown an increase in the release of CCK-8 from STC-1 enteroendocrine cells versus fatty acids from Italian stone pine nuts and several other dietary mono- and polyunsaturated fatty acids.

4. Scientific Evidence by Area of Use

4.1 Appetite Regulation and Weight Management

Preclinical (In Vitro) Evidence

The Korean pine nut (Pinus koraiensis) contains significant levels of certain fatty acids, called pinolenic acid, shown in vitro to induce the release of CCK in STC-1 enteroendocrine cells. This in vitro observation formed the basis for subsequent clinical investigation.

Human Clinical Evidence

The most cited human study in this area used a proprietary Korean pine nut oil concentrate called PinnoThin™. This pine nut oil was investigated in 18 overweight women (BMI = 25–30 kg/m²) who participated in a randomized, double-blind placebo-controlled trial. Volunteers received 3 grams active or olive oil placebo in the form of gel capsules immediately before a carbohydrate test meal. Hormone measures (CCK, GLP-1, PYY peptide, and ghrelin) were taken at 0, 30, 60, 90, 120, 180, and 240 minutes following supplementation. The study demonstrated a significant increase in the satiety hormones CCK and GLP-1 over 4 hours (p < 0.0001); PYY and ghrelin levels were not significantly different from placebo. Subjective appetite scores followed a similarly significant pattern.

A larger subsequent study further tested the free fatty acid (FFA) form of PinnoThin™ on actual food intake. The effects of PinnoThin™ at doses of 2 g, 4 g, and 6 g triglyceride (TG) and 2 g free fatty acid (FFA) on food intake and appetite were examined in a crossover double-blind placebo-controlled randomized counter-balanced design in 42 overweight female volunteers. The 2 g FFA PinnoThin™, given 30 minutes prior to an ad-libitum buffet test lunch, significantly reduced food intake (gram) by 9% (F(4,164) = 2.637, p = 0.036) compared to olive oil control. No significant effect of PinnoThin™ on macronutrient intake or ratings of appetite were observed. Notably, only the free fatty acid form at the 2 g dose produced a significant reduction; the triglyceride forms did not reach significance in this study.

A separate crossover study in overweight/obese individuals examined the combination of hydrolyzed pine nut oil with other oils. Nine overweight/obese individuals completed three 6-hour oral glucose tolerance tests (OGTTs) in a crossover design. At −30 minutes, participants consumed either no oil, 6 g of hydrolyzed pine nut oil (PNO-FFA), or a combination of 3 g hydrolyzed pine nut oil and 3 g olive oil (PNO-OO) in delayed-release capsules. Repeated measures of glucose, insulin, C-peptide, GLP-1, GIP, ghrelin, subjective appetite and gastrointestinal tolerability were done. PNO-FFA augmented GLP-1 secretion from 0–360 min compared to no oil and PNO-OO (p < 0.01).

In a previous study with PinnoThin™, the effects on CCK response took longer to develop for the triglyceride compared to the free fatty acid form (60 min rather than 30 min). A long-term trial including 188 overweight men and women showed that pinolenic acid was present in the blood at 4 and 8 months after daily supplementation with 3 g of PinnoThin™ TG, whereas none was present in the control (olive oil) group.

Evidence strength: The satiety and appetite data are supported by several small randomized controlled trials with mostly consistent direction of effect on CCK and GLP-1. However, sample sizes are small (18–42 participants), the trials are of short duration, and longer-term effects on body weight are not established. The effect on actual ad-libitum food intake was demonstrated with the free fatty acid form but not consistently with the triglyceride form. Overall evidence is preliminary to moderate.

4.2 Lipid Metabolism and Cardiovascular Risk

Preclinical Evidence

Early animal work in rats demonstrated that the dietary effects of Korean pine seed oil (containing approximately 18% pinolenic acid) on various lipid variables were compared with flaxseed oil, safflower oil, and evening primrose oil; in Sprague-Dawley rats fed diets containing 100 g fat and 5 g cholesterol/kg, the hypocholesterolemic activity of pinolenic acid was intermediate between alpha-linolenic and linoleic acids.

Analysis of the fatty acid composition of liver phosphatidylcholine indicated that, in contrast to alpha-linolenic acid, pinolenic acid does not interfere with the desaturation of linoleic acid to arachidonic acid. PNO and PLA improve blood and hepatic lipids in animal models and insulin sensitivity in vitro, and reduce inflammation and modulate immune function in vitro and in animal models.

Proposed Mechanism

Pinolenic acid may enhance hepatic uptake of low-density lipoprotein cholesterol, potentially contributing to cardiovascular health. Cell culture studies with HepG2 cells enriched with concentrated pinolenic acid from Korean pine nut oil showed upregulation of LDL receptor activity, providing a plausible mechanistic explanation for the observed lipid changes in animal studies.

Evidence strength: The cardiovascular lipid evidence is primarily from animal models and in vitro studies. There are no published large-scale human randomized controlled trials specifically testing pinolenic acid as an isolated lipid-lowering intervention. Evidence in this area must be characterized as preliminary and preclinical.

4.3 Inflammation and Rheumatoid Arthritis

Preclinical Evidence

PNLA is emerging as a dietary PUFA and a promising supplement in the prevention of inflammatory disorders or as an alternative therapy. Some studies have shown the health implications of pine nut oil (PNO) and PNLA in weight reduction, lipid-lowering, and anti-diabetic actions, as well as in suppression of cell invasiveness and motility in cancer.

Evidence from Human Cells (Ex Vivo)

In a significant ex vivo study using human patient samples, in pre-clinical studies, pinolenic acid (PNLA), an omega-6-polyunsaturated fatty acid from pine nuts, has shown anti-inflammatory effects. The investigators aimed to study the effect of PNLA in human cell lines and peripheral blood mononuclear cells (PBMCs) from RA patients and healthy controls (HCs). PNLA reduced THP-1 cell migration by 55% (P < 0.001). PNLA significantly reduced monocyte migration, lipid uptake, and macropinocytosis in THP-1 and primary cultures of macrophages in vitro and ex vivo. PNLA also produced a significant reduction in the levels of TNF-α, IL-6, and PGE2 in supernatants of lipopolysaccharide (LPS)-activated PBMCs from RA patients and healthy controls.

A second ex vivo study using purified CD14 monocytes from RA patients found that flow cytometry was used to assess proportions of CD14 monocytes expressing TNF-α, IL-6, IL-1β, and IL-8 in purified monocytes from RA patients after lipopolysaccharide stimulation with or without PNLA pre-treatment. The whole genomic transcriptome profile was investigated by RNA-sequencing. PNLA reduced percentage of monocytes expressing cytokines: TNF-α by 23% (p = 0.048), IL-6 by 25% (p = 0.011), IL-1β by 23% (p = 0.050), IL-8 by 20% (p = 0.066).

Furthermore, in recent bioinformatic studies on human samples, the expression of many mRNAs and microRNAs was regulated by PNLA, indicating potential transcriptional and post-transcriptional regulation of inflammatory and metabolic processes.

Evidence strength: The rheumatoid arthritis and inflammation data are mechanistically compelling but restricted to in vitro and ex vivo work. These studies use human cells from RA patients but do not constitute clinical trials. No large-scale randomized clinical trials in human RA patients have been completed and published with pinolenic acid as an oral supplement. Evidence in this area is preliminary.

4.4 Glucose Metabolism and Insulin Sensitivity

Pine nut oil showed a moderately but significantly improved glucose tolerance compared with maize (corn) oil. Additionally, pure pinolenic acid or its ethyl ester gave strong and highly significant improvements of glucose tolerance. The authors concluded that pinolenic acid is a comparatively potent and efficient dual FFA1/FFA4 agonist that possesses hypoglycemic (anti-diabetic) effects in laboratory mice. This dual receptor agonism—at both FFA1 and FFA4—is mechanistically important because FFA1 has been linked to enhancement of glucose-stimulated insulin secretion, whereas FFA4 has been associated with insulin-sensitizing and anti-inflammatory effects, and both receptors are reported to protect pancreatic islets and promote secretion of appetite and glucose-regulating hormones.

Evidence strength: Preclinical and in vitro evidence is mechanistically consistent. The receptor identification study (Christiansen et al., 2015) represents an important advance. Human clinical trials specifically assessing glycemic outcomes with pinolenic acid supplementation are lacking in the published literature. Evidence is currently preclinical/preliminary.

4.5 Oxidative Stress and Hepatoprotection

Numerous studies have demonstrated that PNA has various health benefits such as antioxidant, weight loss, lipid-lowering, anti-inflammation, appetite control, improving insulin sensitivity, cardio-protection, and anti-cancer properties. One previous study demonstrated that PNA has beneficial effects on antioxidant protective mechanisms in rats fed a high-fat diet.

An in vitro study in HepG2 (human hepatoma) cells subjected to hydrogen peroxide-induced oxidative stress found: PNA improved the survival rate of HepG2 cells induced by H₂O₂ (29.59% increase in the high-dose group), reduced the accumulation of intracellular ROS (65.52%, high-dose group), and reduced the level of intracellular malondialdehyde (MDA; 65.52%, high-dose group). All these results were dose-dependent, indicating that PNA can improve oxidative stress damage of cells.

Evidence strength: This is purely in vitro evidence from cell culture experiments. No human clinical studies on hepatoprotective or antioxidant outcomes have been published. Evidence is preliminary and mechanistic only.

4.6 Blood Pressure

Animal data have suggested a blood pressure effect. When spontaneously hypertensive rats were fed diets containing 100 g fat/kg but free of cholesterol, gamma-linolenic and pinolenic acids, as compared with linoleic acid, increased prostacyclin production and tended to reduce platelet aggregation. In addition, pinolenic acid attenuated the elevation of blood pressure after 5 weeks of feeding.

Evidence strength: Data in this area are from animal studies only. No human clinical trials have specifically tested pinolenic acid for blood pressure outcomes.

4.7 Cancer-Related Research

Some studies have shown the health implications of pine nut oil (PNO) and PNLA in suppression of cell invasiveness and motility in cancer. There are claims of health benefits towards weight reduction, lipid-lowering, diabetes, and inflammatory disorders when pinolenic acid is included in animal diets, and it is reported to suppress cell invasion and motility in cancer.

Evidence strength: Available evidence is entirely preclinical (cell culture studies). No human clinical trials have examined pinolenic acid in cancer prevention or treatment. This area remains very exploratory.

5. Body Systems and Health Areas Associated with Pinolenic Acid

• Gastrointestinal system: Stimulation of CCK release from I-cells in the duodenum and GLP-1 release from L-cells in the ileum; effects on appetite signaling and gastric emptying.
• Cardiovascular system: Preclinical evidence for LDL cholesterol lowering via upregulation of hepatic LDL receptors; animal evidence for prostacyclin production and platelet aggregation effects; antioxidant effects on hepatic cells relevant to non-alcoholic fatty liver disease models.
• Immune/inflammatory system: Reduction of pro-inflammatory cytokine production (TNF-α, IL-6, IL-1β, IL-8) and PGE2 in human monocyte and PBMC cell preparations; modulation of macrophage migration and foam cell formation.
• Metabolic system (glucose/insulin): Dual FFA1/FFA4 agonism linked to improved glucose tolerance and insulin sensitization in animal and in vitro models.
• Antioxidant defense system: Activation of the Nrf2/Keap1 pathway with downstream upregulation of HO-1 and NQO1 antioxidant enzymes in hepatic cell models.

The focus of relevant reviews is on the potential actions of PNLA on inflammation along with modulation of lipid metabolism and oxidative stress, based on data from both in vitro and in vivo experiments, and human findings, including gene expression analysis.

6. Dosage Forms and Dosages Reported in Studies

Pinolenic acid is not commercially available as an isolated pure compound for general supplementation; it is consumed primarily as a constituent of pine nut oil. The following dosages reflect those reported in peer-reviewed clinical and human studies:

• 3 g of Korean pine nut oil (PinnoThin™) taken as gel capsules immediately before a carbohydrate test meal was the dose used in the 18-woman randomized placebo-controlled trial.
• 2 g, 4 g, and 6 g of PinnoThin™ in the triglyceride form (TG) and 2 g in the free fatty acid form (FFA) were tested in a crossover design in 42 overweight female volunteers. The 2 g FFA form, given 30 minutes prior to a meal, significantly reduced food intake by 9% compared to olive oil control.
• 6 g of hydrolyzed pine nut oil (PNO-FFA) or a combination of 3 g hydrolyzed pine nut oil and 3 g olive oil (PNO-OO) were consumed in delayed-release capsules by nine overweight/obese individuals at −30 minutes before oral glucose tolerance testing.
• A long-term trial including 188 overweight men and women used 3 g/day of PinnoThin™ TG supplemented daily over 4 and 8 months.

Regarding absorption, the positional distribution pattern of fatty acids in triacylglycerols affects intestinal absorption. A comparison of lymphatic absorption of pinolenic acid present in structured pinolenic TAG (SPT), where PLA was evenly distributed on the glycerol backbone, versus natural pine nut oil (PNO), where PLA was predominantly at the sn-3 position, found significantly greater amounts of PLA detected in lymph from an emulsion containing SPT (28.5 ± 0.7% dose) than from PNO (26.2 ± 0.6% dose) over 8 hours in a rat lymphatic cannulation model.

7. Safety Considerations and Interactions

7.1 Pine Nut Syndrome (Pine Mouth)

A notable adverse phenomenon associated with pine nut consumption—which is relevant to pinolenic acid-rich preparations—is so-called "pine mouth syndrome." The reported complaints are consistent with a previously described condition called pine mouth syndrome. Although the mechanism remains unknown, pine mouth syndrome should be recognized as an emerging food hypersensitivity in patients presenting with atypical oral complaints to pine nuts. The majority of pine nuts implicated in reported cases were imported from Asia (China, 68.2%) and consumed in a raw state (75.2%). Only 15.7% of consumers in one survey reported additional symptoms such as tingling in the mouth, hives and/or gastrointestinal complaints, suggestive of a possible food allergy or intolerance. Except for a few cases in which oral allergy-like symptoms were noted in individuals with seasonal or tree nut allergies, there was no association between pine mouth symptoms and an allergic condition.

7.2 Allergy

People who are sensitive to pine trees should avoid Korean pine nut. Published case reports document anaphylaxis associated with pine nut ingestion in tree nut-allergic individuals.

7.3 Potential Drug Interactions

Korean pine nut oil might decrease blood pressure; taking it along with medications for high blood pressure might cause blood pressure to go too low. This is consistent with the animal data showing attenuation of blood pressure elevation in hypertensive rats fed pinolenic acid-containing diets.

7.4 Absorption Form and Tolerability

Given the data showing that the triglyceride form of PinnoThin™ may also reduce appetite by increasing CCK release, the lack of any effect of the TG form found in one study could be attributed to the timing of the dosing regime. The free fatty acid form of pine nut oil appears to be absorbed and to exert its gastroenteric effects more rapidly than the triacylglycerol form.

7.5 Overall Evidence Base Limitations

Current treatments for inflammatory conditions are associated with significant side effects and do not completely suppress inflammation. The benefits of diet, especially the role of specific components, are poorly understood. The majority of studies on PUFAs have been on omega-3 fatty acids. This fatty acid—pinolenic acid from pine nuts—typically constitutes up to 20% of its total fatty acids. The overall scientific evidence base for pinolenic acid in human health is at an early stage. Few reviews have specifically focused on the biological and anti-inflammatory effects of PNLA. Most mechanistic data derive from cell culture and animal models, and human clinical trials are small, of short duration, and largely limited to appetite/satiety outcomes. Robust, long-term randomized controlled trials in clinical populations are lacking across virtually all proposed indications.

References

• Takala R, Ramji DP, Choy E. "The Beneficial Effects of Pine Nuts and Its Major Fatty Acid, Pinolenic Acid, on Inflammation and Metabolic Perturbations in Inflammatory Disorders." Int J Mol Sci. 2023;24(2):1171. PMC9861571
• Takala R, Ramji DP, Andrews R, et al. "Anti-inflammatory and immunoregulatory effects of pinolenic acid in rheumatoid arthritis." Rheumatology. 2021;61:992–1004. PMC8889292
• Takala R, et al. "Pinolenic acid exhibits anti-inflammatory and anti-atherogenic effects in peripheral blood-derived monocytes from patients with rheumatoid arthritis." PMC9133073
• Christiansen E, et al. "Activity of dietary fatty acids on FFA1 and FFA4 and characterisation of pinolenic acid as a dual FFA1/FFA4 agonist with potential effect against metabolic diseases." Br J Nutr. 2015. PMID 25916176
• Hughes GM, Boyland EJ, Williams NJ, et al. "The effect of Korean pine nut oil (PinnoThin™) on food intake, feeding behaviour and appetite: A double-blind placebo-controlled trial." Lipids Health Dis. 2008;7:6. PMC2289823
• Phan TT, et al. "Pinolenic Acid in Structured Triacylglycerols Exhibits Superior Intestinal Lymphatic Absorption As Compared to Pinolenic Acid in Natural Pine Nut Oil." PMID 28198188
• PMC8498045 — "Effect of pinolenic acid on oxidative stress injury in HepG2 cells induced by H₂O₂."
• Sugano M, Ikeda I, Wakamatsu K, Oka T. "Influence of Korean pine (Pinus koraiensis)-seed oil containing cis-5,cis-9,cis-12-octadecatrienoic acid on polyunsaturated fatty acid metabolism, eicosanoid production and blood pressure of rats." Br J Nutr. 1994;72(5):775-783. PMID 7826999
• Burdge GC, et al. "A review of the functional effects of pine nut oil, pinolenic acid and its derivative eicosatrienoic acid and their potential health benefits." Prostaglandins Leukot Essent Fatty Acids. 2021. ScienceDirect
• Le Gall M, et al. "A review of the potential health benefits of pine nut oil and its characteristic fatty acid pinolenic acid." Journal of Functional Foods. 2016. ScienceDirect
• "Comparison of the Physicochemical Characteristics of Pinus koraiensis L. Nut Oils from Different Extraction Technologies." ScienceDirect
• Mostin M. "Pine mouth syndrome – an emerging food hypersensitivity?" PMC3354153
• Wikipedia — Pinolenic acid
• Wikipedia — Pine nut oil
• Wikipedia — Pinus koraiensis
• PubChem — Pinolenic acid CID 5312495
• LIPID MAPS — Fatty Acids: Polyunsaturated with Non-Methylene-Interrupted Double Bonds
• UTEP Center for Botanical & Dietary Supplements Research — Korean Pine Nut Fact Sheet
• WebMD Natural Medicines — Korean Pine monograph