Ascorbyl palmitate does not have a specific pharmacological target in the traditional sense, as it is an antioxidant rather than a receptor or enzyme modulator. Its primary mechanism of action is free radical scavenging and inhibition of lipid oxidation. As a lipophilic derivative of vitamin C, it acts as a reducing agent that can donate electrons to neutralize free radicals, thereby preventing oxidative damage to lipids and cell membranes. Its antioxidant activity is attributed to the ascorbyl moiety.

In vitro, ascorbyl palmitate exhibits antioxidant and antiproliferative activities. It scavenges hydroxyl radicals in cell-free systems. In β-carotene-linoleate and lecithin liposome systems, it demonstrates high efficacy as an antioxidant. Its antioxidant activity has been evaluated using DPPH radical scavenging assays, where it shows significant activity. It also exhibits antiproliferative effects, although these are not its primary use.

In vivo, ascorbyl palmitate can decrease free radical formation in pig skin. It is rapidly and extensively hydrolyzed pre-systemically to ascorbic acid and palmitic acid. This suggests that its in vivo effects may be mediated by its hydrolysis products. As a food additive and dietary supplement, its in vivo effects are related to its antioxidant activity and its role as a source of vitamin C. However, specific pharmacological in vivo data are limited.

The in vitro antioxidant activity of ascorbyl palmitate is typically assessed using cell-free assays. The DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging assay measures the compound's ability to scavenge free radicals. The β-carotene-linoleate assay and lecithin liposome systems are used to assess its ability to inhibit lipid oxidation. These cell-free assays provide a measure of the compound's antioxidant capacity without the confounding effects of cellular metabolism or uptake.

In vitro cellular assays for ascorbyl palmitate assess its effects on cell viability and its ability to protect cells from oxidative stress. Cells can be treated with ascorbyl palmitate and then exposed to an oxidative insult, such as hydrogen peroxide or UV radiation. Cell viability is measured, and markers of oxidative stress, such as lipid peroxidation, can be assessed. These assays demonstrate the compound's ability to protect cells from oxidative damage.

In vivo animal studies for ascorbyl palmitate are not extensively detailed in the available literature. One study evaluated its ability to decrease free radical formation in pig skin. As a food additive and dietary supplement, its in vivo effects are typically assessed in the context of nutrition and toxicology rather than pharmacology. Studies on its absorption, metabolism, and excretion have been conducted, but specific efficacy studies are limited.

Absorption, Distribution and Excretion
Studies have found that when ascorbate palmitate is integrated into the human erythrocyte membrane, it can protect erythrocytes from oxidative damage and protect α-tocopherol (a lipid-soluble antioxidant) from free radical oxidation. However, the protective effect of ascorbate palmitate on cell membranes has only been demonstrated in vitro. Oral administration of ascorbate palmitate may not result in significant integration into cell membranes, as most of the ascorbate palmitate appears to be hydrolyzed (broken down into palmitate and ascorbic acid) in the human digestive tract before absorption. The ascorbic acid released from the hydrolysis of ascorbate palmitate appears to have the same bioavailability as ascorbic acid alone. When ascorbate palmitate was applied topically to guinea pigs, it penetrated the skin barrier, increasing the ascorbic acid content in the skin, liver, and blood by 8, 7, and 4 times, respectively, compared to the control group that did not receive ascorbate palmitate treatment. (14)C-ascorbate palmitate was applied to the skin of scurvy guinea pigs. Following topical application, ascorbic acid concentrations in the skin, liver, kidneys, and blood were 4 to 8 times higher than in the control group. Ascorbate palmitate dissolved in sodium taurocholate solution was hydrolyzed using homogenates from guinea pig liver, pancreas, and intestines. The small intestine and pancreas homogenates hydrolyzed approximately 80% of the ascorbate palmitate into free ascorbic acid. …Guinea pigs were orally administered ascorbate palmitate equivalent to 20 mg of ascorbic acid, and the amount of free ascorbic acid excreted in urine was measured. Excretion within 0–24 hours was higher than within 24–48 hours. A similar trend in free ascorbic acid levels in these organs was observed when L-ascorbic acid was used instead of ascorbic acid, but the opposite trend was observed when ascorbate palmitate was used.

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Metabolism/Metabolites
Vitamin C (ascorbic acid) is a non-enzymatic antioxidant that plays an important role in protecting the lungs from oxidative damage, and its levels are reduced in the alveolar fluid of horses with airway inflammation. To investigate potential treatment options in species capable of ascorbic acid synthesis, this study employed a 3×3 Latin square design to investigate the effects of oral supplementation with two forms of ascorbic acid (each equivalent to 20 mg of ascorbic acid per kg body weight) on the pulmonary and systemic antioxidant status of six healthy foals. After two weeks of ascorbate palmitate supplementation, the mean plasma ascorbic acid concentration was significantly increased compared to the control group (29±5 and 18±7 μmol/L, respectively; p<0.05). Ascorbic acid-2-monophosphate (a more stable form of ascorbic acid) also increased the mean plasma ascorbic acid concentration, but the difference was not significant (23±1 μmol/L; p=0.07). Compared to the control group, supplementation with ascorbate palmitate or ascorbate-2-monophosphate increased the concentration of ascorbic acid in the bronchoalveolar lavage fluid of five out of six ponies (30 ± 10, 25 ± 4, and 18 ± 8 μmol/L, respectively; p < 0.01). Neither supplementation altered the concentrations of glutathione, uric acid, or α-tocopherol in plasma or bronchoalveolar lavage fluid. In conclusion, ascorbic acid supplementation (20 mg/kg body weight) increases the concentration of ascorbic acid in alveolar fluid in animals capable of synthesizing ascorbic acid. Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) are known to have blocking effects, but compared to placebo, the addition of ascorbate palmitate (AP) significantly improved skin moisturization in both short-term (p < 0.001) and long-term (p < 0.01) studies, as was the case with both SLNs and NLCs. In the second part of the study, it was found that SLN and NLC reduced the permeation of AP through isolated human skin by approximately 1/2 and 2/3 times that of NE, respectively (p < 0.001 and p < 0.01)...
6-O-palmitoyl-L-ascorbic acid was dissolved in sodium taurocholate solution and hydrolyzed with homogenates of guinea pig pancreas, liver, and intestines.
Ascorbyl palmitate is rapidly and extensively hydrolyzed pre-systemically to ascorbic acid and palmitic acid. This hydrolysis occurs in the gastrointestinal tract before absorption. As a lipophilic compound with a log P of approximately 6.5, it partitions into lipid phases. However, its pharmacokinetics are largely determined by the absorption and metabolism of its hydrolysis products, ascorbic acid and palmitic acid. Detailed pharmacokinetic parameters are not available.

Interactions
In male ME1 mice, after hepatotoxicity was induced by acetaminophen (600 mg/kg), acetaminophen metabolites covalently bound to hepatic proteins, leading to depletion of non-protein sulfhydryl groups in the liver after 2 hours and a significant increase in plasma alanine aminotransferase activity after 24 hours. Co-administration of acetaminophen with ascorbate palmitate reduced this binding at 2 and 4 hours (to 31% and 22%, respectively), decreased non-protein sulfhydryl depletion and aminotransferase activity, and completely prevented the 35% mortality observed 24 hours after acetaminophen monotherapy. Ascorbate palmitate appears to prevent liver injury by clearing active acetaminophen metabolites and protecting against reduced hepatic glutathione. Low-dose topical application of ascorbate palmitate inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ornithine decarboxylase activity, tumorigenesis, and DNA synthesis in mouse epithelial cells. A single topical application of 2 nmol TPA followed by 4 μmol ascorbate palmitate inhibited 60-70% of tumor growth. When mice with induced tumor growth were administered 5 nmol TPA and 5 pmol ascorbate palmitate twice weekly, the tumor inhibition rate reached 91% per mouse. This work…aimed to determine the antioxidant properties of ascorbic acid's lipid-soluble derivative, ascorbate-6-palmitate. Ascorbate-6-palmitate reduced intracellular reactive oxygen species levels after UVB irradiation. Treatment of keratinocytes with ascorbate-6-palmitate inhibited UVB-mediated activation of epidermal growth factor receptor, extracellular signal-regulated kinases 1 and 2, and p38 kinase, attributed to its ability to prevent the consumption of reduced glutathione and scavenge hydrogen peroxide. However, ascorbate-6-palmitate significantly promoted UVB-induced lipid peroxidation, c-Jun N-terminal kinase activation, and cytotoxicity. It has been reported that end products of lipid peroxidation, such as 4-hydroxy-2-nonenal, can mediate the activation and cytotoxicity of stress-activated protein kinases in epithelial cells. The lipid components of ascorbic acid-6-palmitate may be involved in the generation of oxidized lipid metabolites toxic to epidermal cells. Data indicate that although ascorbic acid-6-palmitate possesses antioxidant properties, it may exacerbate skin damage following physiological doses of ultraviolet radiation. ...The effects of various antioxidants, including ascorbic acid palmitate, on rabbit platelet function were investigated using thromboxane B2 synthesis and enzyme immunoassay. When ascorbic acid palmitate was added concurrently, concentrations of 1.0 × 10⁻⁵ M and above inhibited A-23187-induced thromboxane B2 synthesis; concentrations of 1. × 10⁻⁷ M also inhibited thrombin-induced thromboxane B2 synthesis. Unless platelets are pre-stimulated with thrombin, pretreatment of platelets with ascorbate palmitate also inhibits thromboxane B2 synthesis induced by both agonists. Agonist-induced platelet activation was also significantly reduced when rabbits were fed the appropriate dose (ADI) of ascorbate palmitate for 5 consecutive days. For more complete data on interactions of ascorbate palmitate (14 in total), please visit the HSDB record page.

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Non-human toxicity values
Guinea pig dermal LD50 >3 g/kg
Mouse oral LD50 >2 g/kg /33% suspension/
Rat oral LD50 >5 g/kg /33% suspension/
Ascorbyl palmitate is generally recognized as safe (GRAS) for use as a food additive. Studies indicate that it is not a skin irritant or sensitizer. It has not shown mutagenic or carcinogenic effects in available data. However, high doses may cause gastrointestinal discomfort. Its safety profile supports its widespread use as a food additive and dietary supplement. It is considered non-toxic at the levels typically used in food and cosmetic products.

Ascorbate palmitate is a fatty acid ester.

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Mechanism of Action
…This study used a gap junction intercellular communication (GJIC) model to investigate whether L-ascorbate-6-palmitate (AAP), an amphiphilic derivative of ascorbic acid (AA), possesses chemopreventive activity. Both AAP and ascorbic acid (AA) exhibited dose-dependent free radical scavenging activity and inhibited hydrogen peroxide (H₂O₂)-induced intracellular reactive oxygen species (ROS) generation in normal rat liver epithelial cells. However, unexpectedly, AAP did not prevent H₂O₂-induced GJIC inhibition; instead, it synergistically inhibited GJIC with H₂O₂. AAP inhibited GJIC in a dose-dependent and reversible manner. This inhibition was not due to the conjugated lipid structure of AAP, as palmitic acid treatment alone under the same conditions did not inhibit GJIC. In the presence of the mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK) inhibitor U0126, the inhibitory effect of AAP on GJIC was restored, but not in the presence of other signaling inhibitors and antioxidants (PKC inhibitors, EGFR inhibitors, NADPH oxidase inhibitors, catalase, vitamin E, or AA), indicating that the MEK signaling pathway plays a key role in the GJIC inhibitory activity of AAP. Phosphorylation of ERK and connexin 43 (Cx43) was observed after AAP treatment, and U0126 could reverse this phosphorylation. These results suggest that AAP-induced GJIC inhibition is mediated by activation of the MEK-ERK pathway, leading to phosphorylation of Cx43.

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Therapeutic Uses
Antimutagenic agent; Antioxidant
Ascorbate palmitate has vitamin C activity roughly equivalent to L-ascorbic acid. …Vitamin C is an essential cofactor for prolyl hydroxylase and lysyl hydroxylase, enzymes involved in the biosynthesis of intracellular collagen.
/Experimental Therapy/ QR-333 is a topical compound containing quercetin (a flavonoid compound with aldose reductase inhibitory activity), ascorbate palmitate, and vitamin D3. Its formulation is designed to reduce oxidative stress, which contributes to peripheral diabetic neuropathy, thereby alleviating its symptoms. This randomized, placebo-controlled, double-blind trial enrolled 34 men and women (aged 21–71 years) with type 1 or type 2 diabetes and diabetic neuropathy. Subjects applied either QR-333 or a placebo (2:1 ratio) three times daily for four weeks to the symptom-affected feet. …QR-333 significantly reduced the severity of numbness, tremor-like pain, and irritation. Overall quality of life and specific quality of life indicators also improved. QR-333 was well tolerated. In the QR-333 group, 11 patients reported 23 adverse events (all mild or moderate); in the placebo group, 4 patients reported 5 adverse events (all moderate). One patient using QR-333 reported two tingling sensations, which was the only adverse event considered potentially related to the study treatment…
The presence of ascorbyl palmitate in oral supplements helps increase the ascorbic acid content in the supplement and may help protect the fat-soluble antioxidants in the supplement.
Ascorbyl palmitate is a lipophilic derivative of vitamin C that is used as an antioxidant in food, cosmetic, and pharmaceutical applications. It is a dietary supplement that provides a fat-soluble form of vitamin C. Its main advantage over ascorbic acid is its ability to partition into lipid phases, making it effective at preventing lipid oxidation in fatty foods and oils. It retains antioxidant activity under high heat, whereas unmodified ascorbic acid degrades rapidly. It is not a drug and is not approved for therapeutic use.

C22H38O7

414.53

414.261

137-66-6

54680660

White to off-white solid powder

1.2±0.1 g/cm3

512.7±50.0 °C at 760 mmHg

115-118 °C(lit.)

164.4±23.6 °C

0.0±3.0 mmHg at 25°C

1.521

6.07

3

7

18

29

515

2

CCCCCCCCCCCCCCCC(=O)OC[C@@H]([C@@H]1C(=C(C(=O)O1)O)O)O

QAQJMLQRFWZOBN-LAUBAEHRSA-N

InChI=1S/C22H38O7/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-18(24)28-16-17(23)21-19(25)20(26)22(27)29-21/h17,21,23,25-26H,2-16H2,1H3/t17-,21+/m0/s1

(S)-2-((R)-3,4-dihydroxy-5-oxo-2,5-dihydrofuran-2-yl)-2-hydroxyethyl palmitate

BRN-0096552 6-Palmitoylascorbic acid NSC 402451CCRIS-3930Ascorbyl palmitateBRN 0096552 CCRIS 3930 HSDB 418 NSC 402451 BRN0096552 Vitamin C palmitate CCRIS3930 HSDB418 NSC 402451 HSDB-418

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~100 mg/mL (~241.24 mM)
H2O : < 0.1 mg/mL

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.03 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)