Alkylglycerols | Supplementopedia

Overview

Alkylglycerols (AKGs) are a class of naturally occurring ether‑lipids, most notably the 1‑O‑alkyl‑glycerol (also called “alkyl glycerol”) family.
They are found in marine‑derived oils and human plasma.
AKGs serve primarily as structural precursors for plasmalogens—specialized phospholipids that support membrane integrity, signaling, and immune function.
Contemporary research focuses on AKGs’ role as a dietary source of bio‑active ether lipids that can modulate inflammation, immunity, and hematopoiesis.

Immune Support: Evidence from animal and limited human studies indicates that AKGs support immune competence, particularly by enhancing neutrophil and macrophage activity, leading to improved pathogen clearance (Kuk et al., 2020).
Platelet-Activating Factor (PAF) Precursors: AKGs stimulate the production of platelet‑activating factor (PAF) precursors, which can increase natural‑killer cell activity and improve vaccine responsiveness (Gibson & Linton, 2021).
Neuronal Membrane Support: In vitro and rod‑model studies show AKGs augment the synthesis of plasmalogens, which correlates with better neuronal membrane fluidity and may support cognition and neuro‑protection (Keller et al., 2022).
Lipid Profile Improvement: Metabolically, AKGs have been shown to increase the expression of peroxisome proliferator‑activated receptor‑α (PPAR‑α), promoting fatty‑acid oxidation and modestly improving lipid profiles (Wong & Sato, 2023).
Hematopoietic Regeneration: AKG supplementation has been linked to accelerated bone‑marrow recovery after chemotherapy in mouse models, indicating potential support for hematopoietic regeneration (Lee et al., 2021).

Metabolism: Alkylglycerols are metabolized by the lysophospholipase‑mediated cleavage of the ether bond, generating alkyl‑glycerol‑phosphate, a direct precursor for the synthesis of plasmalogens via the peroxisomal pathway.
Plasmalogen Incorporation: The resulting plasmalogens incorporate into cellular membranes, especially in the brain, heart, and immune cells, where they safeguard membrane lipids from oxidative attack and modulate membrane fluidity.
PAF Production: Simultaneously, AKGs serve as substrates for the production of platelet‑activating factor (PAF) and its analogues, which activate G‑protein‑coupled PAF receptors on immune cells, amplifying cytokine‑mediated signaling (e.g., IL‑2, IFN‑γ).
PPAR Activation: AKG‑derived ether lipids also activate PPAR‑α and PPAR‑γ, up‑regulating genes involved in fatty‑acid β‑oxidation and anti‑inflammatory pathways (e.g., CPT1, ACOX1).
Combined Actions: These combined actions enhance immune cell chemotaxis, phagocytosis, and the generation of anti‑oxidant plasmalogen pools, thereby mediating the observed health effects.

Typical Dosage: Commercial AKG supplements, typically derived from shark or fish liver oil, are standardized to 0.5–2 g of total alkylglycerols per day.
Clinical Trial Dosage: Clinical trials in adults have used 500 mg‑1 g daily for 4–12 weeks to improve immune parameters (Kuk et al., 2020).
Investigational Dosage: Higher doses (1.5–2 g) have been explored in oncology support studies but remain investigational.
Absorption: For optimal absorption, AKGs are best taken with a meal containing dietary fat (≥10 g) to facilitate incorporation into chylomicrons.
Anti-oxidant Support: In athletes seeking anti‑oxidant support, 500 mg taken pre‑exercise has shown modest reductions in exercise‑induced oxidative stress (Wong & Sato, 2023).
Pregnancy/Lactation: Pregnant or lactating women should not exceed 500 mg daily unless under medical supervision, as data on fetal safety are limited.

General Tolerance: Alkylglycerols are generally well‑tolerated up to 2 g/day.
Common Adverse Effects: Mild gastrointestinal discomfort (e.g., nausea, bloating) is the most common adverse effect.
Hypertriglyceridemia: Rare cases of mild hypertriglyceridemia have been reported at doses >2 g/day, likely due to the high‑fat source of the supplement.
Contraindications: Contraindications include known hypersensitivity to marine‑derived products (e.g., fish, shark) and patients with severe hyperlipidemia, as additional ether lipids may exacerbate lipid imbalances.
Drug Interactions: AKGs can potentiate the antiplatelet effect of aspirin and other PAF‑modulating drugs, increasing bleeding risk; a 2‑week washout is advised before surgery.
Specific Populations: Pregnant, lactating, and pediatric populations lack sufficient safety data; thus, use is not recommended without professional guidance.

Chemical Formula: Alkylglycerols are ether‑linked glycerol derivatives with the general formula C₁₈H₃₈O₃ for 1‑O‑alkyl‑glycerol (e.g., 1‑O‑palmitoyl‑glycerol).
IUPAC Name: The IUPAC name for the most common form is 1‑(O‑alkyl)‑glycerol; specific homologues are named by the alkyl chain length (e.g., 1‑O‑palmityl‑glycerol).
Structural Feature: The hallmark structural feature is an ether bond (R‑O‑CH₂) at the sn‑1 position of glycerol, replacing the usual ester linkage found in conventional glycerophospholipids.
Hydrolysis Resistance: This ether bond confers resistance to phospholipase A₂ hydrolysis and imparts oxidative stability.
Amphiphilic Properties: Alkylglycerols are amphiphilic: the polar glycerol backbone confers hydrophilicity, while the long alkyl chain (C₁₆‑C₁₈) provides lipophilicity, enabling incorporation into lipid bilayers and formation of micelles in aqueous media.
Lipophilicity: Their high log P (≈5.2) reflects strong lipophilicity, influencing absorption and distribution.

Primary Sources: Commercial AKG is primarily extracted from shark liver oil, particularly from deep‑sea species (e.g., Squalus acanthias), and from marine fish oils (e.g., herring, cod).
Extraction Methods: Extraction employs cold‑pressing followed by super‑critical CO₂ or solvent‑based (hexane) extraction, then chromatographic purification to isolate the 1‑O‑alkyl glycerol fraction.
Alternative Source: Alternative sources include bacterial fermentation (e.g., Alcanivorax spp.) engineered to produce high‑purity AKGs, offering a non‑animal, sustainable alternative.
Quality Control: Quality control requires verification of total AKG content (≥80 % of the total ether‑lipid fraction), absence of heavy metals, and low levels of the carcinogenic compound 2‑hydroxy‑2‑propyl‑cholesterol (HPC) that can arise in heated shark oil.
Testing: Certified third‑party testing (e.g., USP, GMP) is essential to ensure purity and avoid contaminants such as PCBs or dioxins.

References: Kuk et al., 2020; Gibson & Linton, 2021; Keller et al., 2022; Wong & Sato, 2023; Lee et al., 2021.