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Palmitoleic Acid
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Palmitoleic Acid

Palmitoleic acid is an omega-7 monounsaturated fatty acid (16:1n-7), found both in the diet and endogenously synthesized from palmitic acid via the enzyme Stearoyl-CoA desaturase-1. 

Recognized as an adipokine, it is released from fat cells and influences various organs. 

Dietary sources of palmitoleic acid include macadamia oil, sea buckthorn oil, and sardine oil. 

Biochemically, palmitoleic acid is produced in the liver and adipose tissue, with its synthesis regulated by diet, hormones, and metabolic state. It exists in both cis and trans isomers, with the cis form produced endogenously and the trans form derived from dietary vaccenic acid. 

After synthesis, it is incorporated into triglycerides, phospholipids, waxes, and cholesterol esters, playing roles in triglyceride metabolism and serving as an energy source through beta-oxidation. 

Palmitoleic acid offers multiple health benefits, including improved insulin sensitivity, anti-inflammatory effects, cardiovascular health benefits, and potential for enhancing skin hydration and barrier function. 

However, elevated levels have been linked to obesity and certain cancers, highlighting the need for balanced intake and further research into its therapeutic potential.

What is Palmitoleic Acid?

Palmitoleic acid is an omega-7 monounsaturated fatty acid (16:1n-7). It is available in the diet, and it can also be endogenously synthesized from palmitic acid. [9.]

Palmitoleic acid is considered an adipokine, a molecule released from fat cells that exerts its influence on distant organs. [6.] 

Sources of Palmitoleic Acid

Palmitoleic acid is biosynthesized from palmitic acid through the action of the enzyme Stearoyl-CoA desaturase-1. [9.] Vaccenic acid is another precursor, which is converted to trans-palmitoleic acid. 

Dietary palmitoleic acid is found in trace amounts in most foods, with higher concentrations in:

  • Macadamia oil (17%) [5.] 
  • Sea buckthorn oil (19-29%) [18.] 
  • Sardine oil (8-9%) [8.] 

Biochemistry of Palmitoleic Acid [6.] 

Endogenous Synthesis

Palmitoleic acid is primarily produced through de novo lipogenesis in the liver and adipose tissue via the enzyme Stearoyl-CoA desaturase 1 (SCD1) from palmitic acid.

Biosynthesis regulation is influenced by factors such as diet, hormones, and overall metabolic state.

Isomers

The cis isoform (cis-palmitoleate) is produced endogenously, while the trans isoform can be generated from dietary vaccenic acid.

Role in Triglycerides

After synthesis, palmitoleic acid is incorporated into triglycerides, phospholipids, waxes, and cholesterol esters. It's a common constituent of human adipose tissue glycerides.

Beta Oxidation

Palmitoleic acid is rapidly oxidized compared to other fatty acids. Through beta oxidation, it can serve as an energy source for cells.

Metabolism Regulation

Studies suggest palmitoleic acid may provide multiple metabolic benefits including improving insulin sensitivity in liver and skeletal muscles; PPAR-alpha activation; and increased lipid metabolism. [6.] 

Health Benefits of Palmitoleic Acid

Improves Insulin Sensitivity [7., 13.] 

Palmitoleic acid may enhance insulin sensitivity in liver and skeletal muscles, and it could help reduce the risk of diabetes.

Anti-Inflammatory Effects [7., 13.] 

Palmitoleic acid has been shown to suppress inflammatory markers in adipose tissue.

Cardiovascular Health Benefits [13.] 

Potentially decreases serum triglyceride and cholesterol levels, and may normalize levels of HDL and LDL-cholesterol in individuals with hypercholesterolemia.

Supplementation with macadamia oil, which has a high proportion of palmitoleic acid, promotes a decrease in serum triglyceride and cholesterol levels. [13.] 

Metabolic Health [7., 13.] 

Due to its beneficial effects on glucose and lipid metabolism, palmitoleic acid could help prevent or ameliorate metabolic syndrome.

Palmitoleic acid has demonstrated the ability to increase white adipocytes GLUT4 content and glucose uptake. [7.] 

Liver Health [7., 15.] 

Palmitoleic acid was shown to reduce liver inflammation, hepatic steatosis, and liver enzymes in mice. [15.] 

Immune System Modulation [13.] 

Palmitoleic acid exerts a suppressive effect on the immune system by reducing lymphocyte proliferation and decreasing the production of inflammatory cytokines. 

This effect is characterized by reduced Th1 and Th17 responses and modulation of co-stimulatory and apoptotic molecules. 

Palmitoleic acid has potential as an anti-inflammatory agent in immune-related disorders.

PPAR Activation [19.] 

Palmitoleic acid demonstrates an ability to activate PPARα and PPARγ which provide multiple benefits for cardiometabolic health and weight management. [19.] 

Activation of PPARα and PPARγ offers a wide range of benefits including improved lipid metabolism, enhanced insulin sensitivity, anti-inflammatory effects, better cardiovascular health, and efficient energy homeostasis.  [17., 19.] 

These benefits make PPAR activation a promising therapeutic target for managing metabolic diseases, cardiovascular conditions, obesity, and inflammation-related disorders.

Skin Health

Palmitoleic acid improves skin hydration and barrier function but shows less significant effects on elasticity and wrinkle reduction. [10.] 

Diseases Associated with Palmitoleic Acid

Obesity

Elevated levels of palmitoleic acid have been seen in obese children, which is believed to be due to increased Stearoyl-CoA desaturase-1 activity stimulated by leptin dysregulation. [11.] 

In men, elevated levels of triglycerides and palmitoleic acid correlated with abdominal obesity. [12.] Elevated palmitoleic acid has been seen in obese men and women. [1.] 

Insulin Resistance

Lower levels of palmitoleic acid have been associated with increased insulin resistance. [16.] 

Cancer

Increased palmitoleic acid levels have been linked to higher risks and incidence of certain cancers, including breast and prostate cancer.

SCD1 activity, which increases palmitoleate production, is associated with cancer cell survival and proliferation.

How Much Saturated Fat Should I Eat?

The Dietary Guidelines for Americans 2020-2025 (DGA) recommend that individuals consume no more than 10 percent of daily calories as saturated fat. [2.] 

In one investigation, individuals who kept saturated fat below 10% of total calories consumed an average of 236 fewer calories/day than those who consumed more than 10% of their total calories from saturated fat. [3.] 

The daily saturated fat intake in those consuming >10% of total calories as saturated fat came primarily from an increased consumption of meat, eggs, milk and cheese. [3.] 

Palmitoleic Acid Laboratory Testing

Lab Test Information, Sample Collection and Preparation

Fatty acid levels are commonly tested in the blood. Sample collection may require a venipuncture, or a blood spot.

Fasting is required prior to sample collection. It is also important to consult with the ordering provider prior to sample collection, as certain supplements may need to be avoided prior to collection. Do not stop or alter medication use without consulting with a licensed medical provider.

Interpretation of Palmitoleic Acid Levels

Optimal Levels of Palmitoleic Acid

Fatty acid analysis is often done by examining palmitoleic acid levels as a % of total fatty acids present in the blood. 

Lab companies typically report optimal levels < 0.64% of total fatty acid content. [14.] 

Clinical Significance of Elevated Levels of Palmitoleic Acid

While robust levels of palmitoleic acid are associated with health benefits, elevated levels of Palmitoleic Acid in the bloodstream have been associated with obesity.

Individuals with elevated levels of palmitoleic acid alongside other markers of impaired cardiometabolic health should have a thorough dietary assessment and individualized treatment plan containing diet and exercise recommendations. Overweight or obese individuals should be provided weight loss support. 

Additional therapies should be offered on an individual basis, including supplements or medications. 

Clinical Significance of Decreased Levels of Palmitoleic Acid

Decreased levels of palmitoleic acid may be seen in individuals with insulin resistance, chronic inflammation, or other indications of cardiometabolic disease.

Palmitoleic Acid Supplements

Palmitoleic acid supplements have gained attention for their potential health benefits, particularly in relation to skin health, metabolic function, and inflammation reduction. 

A recent randomized, double-blind, placebo-controlled study found that oral supplementation with 500 mg/day of palmitoleic acid for 12 weeks significantly improved skin barrier function, including skin hydration and transepidermal water loss, in adult women. [10.]

Additionally, palmitoleic acid has been reported to have beneficial effects on insulin sensitivity, cholesterol metabolism, and hemostasis. [6., 7., 13.] 

Palmitoleic acid supplements have become commercially available, providing an alternative source for increasing palmitoleic acid levels in the body. 

Availability and Forms

Palmitoleic acid supplements are typically derived from plant sources, such as macadamia nuts or sea buckthorn berries, which naturally contain small amounts of this fatty acid. These supplements are available in various forms, including softgel capsules, liquid oils, and powders.

Potential Benefits and Risks

While research on the specific benefits of palmitoleic acid supplementation is ongoing, some potential benefits have been suggested based on the observed associations between higher palmitoleic acid levels and improved metabolic health markers. 

These include improved insulin sensitivity, reduced inflammation, and a more favorable lipid profile.

However, it is important to note that the long-term safety and efficacy of palmitoleic acid supplementation have not been extensively studied, and potential risks or interactions with medications should be considered. 

As with any dietary supplement, it is advisable to consult with a healthcare professional before incorporating palmitoleic acid supplements into one's regimen.

Safety Considerations

As with any supplement, it is crucial to purchase palmitoleic acid products from reputable manufacturers and to follow the recommended dosages and usage guidelines. Excessive intake or improper use of supplements can potentially lead to adverse effects or interactions with medications or underlying health conditions.

Biomarkers to Test Alongside Palmitoleic Acid 

In certain cases, additional assessment of cardiometabolic health may be warranted.

C-reactive protein (CRP)

  • An inflammatory marker associated with cardiovascular risk
  • Elevated levels may indicate systemic inflammation

Lipid Profile

  • Includes total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides
  • Provides into lipid metabolism, which is an important cardiovascular risk factor

Hemoglobin A1c (HbA1c)

  • Reflects average blood glucose levels over the past 2-3 months
  • Important for assessing diabetes risk and glucose metabolism

How to Support Healthy Fatty Acid Levels

Diet and lifestyle are foundational to healthy fatty acid levels in the body. 

Consume a Balanced Diet Rich in Omega-3 Fatty Acids

Include fatty fish like salmon, mackerel, sardines, and herring 2-3 times per week

Add plant-based sources like flaxseeds, chia seeds, and walnuts

Limit Intake of Saturated and Trans Fats

Reduce consumption of processed foods, fried foods, and high-fat dairy products

Choose lean meats and low-fat dairy options

Increase Monounsaturated Fat Intake

Use olive oil, avocados, nuts, and seeds in cooking and as snacks

Maintain a Healthy Omega-6 to Omega-3 Ratio

Aim for a ratio of 4:1 or lower regarding your dietary intake

Reduce consumption of vegetable oils high in omega-6 (e.g., corn, soybean, sunflower)

Include Sources of Medium-Chain Triglycerides (MCTs)

Incorporate coconut oil or MCT oil in moderation for gut health 

Consume Fiber-Rich Foods

Eat plenty of fruits, vegetables, whole grains, and legumes

Stay Hydrated

Drink adequate water throughout the day

Exercise Regularly

Engage in moderate-intensity aerobic exercise for at least 150 minutes per week

Include strength training exercises 2-3 times per week

Get Adequate Sleep

Aim for 7-9 hours of quality sleep per night

Limit Alcohol Consumption

If you drink, do so in moderation (up to 1 drink per day for women, up to 2 for men)

Avoid Smoking and Exposure to Secondhand Smoke

Smoking increases inflammation which has negative effects on overall health [4.] 

Consider Supplementation Under Medical Supervision

Fish oil or algae-based omega-3 supplements if dietary intake is insufficient

Maintain a Healthy Weight

Achieve and maintain a BMI within the healthy range (18.5-24.9)

Control Blood Sugar Levels

Follow a low-glycemic diet if prone to insulin resistance or diabetes

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See References

[1.] Alsharari ZD, Ulf Risérus, Leander K, et al. Serum Fatty Acids, Desaturase Activities and Abdominal Obesity – A Population-Based Study of 60-Year Old Men and Women. PloS one. 2017;12(1):e0170684-e0170684. doi:https://doi.org/10.1371/journal.pone.0170684

[2.] Bowman S, Clemens J, Friday J, et al. Food Patterns Equivalents Database 2017-2018: Methodology and User Guide Acknowledgement of Reviewers We Acknowledge the Following Individuals for Reviewing FPED 2017-2018 Methodology and User Guide, Associated Mean Intake Tables, and FPED and FPID Databases.; 2020. Accessed May 22, 2024. https://www.ars.usda.gov/ARSUserFiles/80400530/pdf/fped/FPED_1718.pdf

[3.] Bowman SA, Clemens JC. Saturated Fat and Food Intakes of Adults: What We Eat in America, NHANES 2017-2018. 2022 May. In: FSRG Dietary Data Briefs [Internet]. Beltsville (MD): United States Department of Agriculture (USDA); 2010-. Dietary Data Brief No. 43. Available from: https://www.ncbi.nlm.nih.gov/books/NBK588575/

[4.] Elisia, I., Lam, V., Cho, B. et al. The effect of smoking on chronic inflammation, immune function and blood cell composition. Sci Rep 10, 19480 (2020). https://doi.org/10.1038/s41598-020-76556-7

[5.] Fard, A.M., Turner, A.G., and Willett, G.D. High-resolution electrospray-ionization fourier-transform ion cyclotron resonance and gas chromatography-mass spectrometry of macadamia nut oil. Aus. J. Chem. 56(5), 499-508 (2003).

[6.] Frigolet ME, Gutiérrez-Aguilar R. The Role of the Novel Lipokine Palmitoleic Acid in Health and Disease. Adv Nutr. 2017 Jan 17;8(1):173S-181S. doi: 10.3945/an.115.011130. PMID: 28096141; PMCID: PMC5227969.

[7.] Guo X, Jiang X, Chen K, et al. The Role of Palmitoleic Acid in Regulating Hepatic Gluconeogenesis through SIRT3 in Obese Mice. Nutrients. 2022;14(7):1482-1482. doi:https://doi.org/10.3390/nu14071482

[8.] Heri Suseno S, Dyah Puri Sintoko E, M. Jacoeb A, Fitriana N. Sardine Oil Purification with Winterization. Oriental Journal of Chemistry. 2017;33(6):3150-3159. doi:https://doi.org/10.13005/ojc/330658

[9.] Hu W, Fitzgerald M, Topp B, Alam M, O’Hare TJ. A review of biological functions, health benefits, and possible de novo biosynthetic pathway of palmitoleic acid in macadamia nuts. Journal of Functional Foods. 2019;62:103520. doi:https://doi.org/10.1016/j.jff.2019.103520

[10.] Koh YG, Seok J, Park JW, Kim KR, Yoo KH, Kim YJ, Kim BJ. Efficacy and safety of oral palmitoleic acid supplementation for skin barrier improvement: A 12-week, randomized, double-blinded, placebo-controlled study. Heliyon. 2023 May 26;9(6):e16711. doi: 10.1016/j.heliyon.2023.e16711. PMID: 37292315; PMCID: PMC10245245.

[11.] Okada T, Furuhashi N, Kuromori Y, Miyashita M, Iwata F, Harada K. Plasma palmitoleic acid content and obesity in children. Am J Clin Nutr. 2005 Oct;82(4):747-50. doi: 10.1093/ajcn/82.4.747. PMID: 16210702.

[12.] Paillard F, Catheline D, Duff FL, Bouriel M, Deugnier Y, Pouchard M, Daubert JC, Legrand P. Plasma palmitoleic acid, a product of stearoyl-coA desaturase activity, is an independent marker of triglyceridemia and abdominal adiposity. Nutr Metab Cardiovasc Dis. 2008 Jul;18(6):436-40. doi: 10.1016/j.numecd.2007.02.017. Epub 2008 Feb 20. PMID: 18068341.

[13.] Passos, M.E.P., Alves, H.H.O., Momesso, C.M. et al. Differential effects of palmitoleic acid on human lymphocyte proliferation and function. Lipids Health Dis 15, 217 (2016). https://doi.org/10.1186/s12944-016-0385-2

[14.] Rupa Health. Essential & Metabolic Fatty Acids Sample Report.pdf. Google Docs. Accessed July 18, 2024. https://drive.google.com/file/d/1cxCUYPBMXMtNT22snzoOnNkF5QUEZof0/view

[15.] Souza CO, Teixeira AAS, Biondo LA, Silveira LS, de Souza Breda CN, Braga TT, Camara NOS, Belchior T, Festuccia WT, Diniz TA, Ferreira GM, Hirata MH, Chaves-Filho AB, Yoshinaga MY, Miyamoto S, Calder PC, Sethi JK, Rosa Neto JC. Palmitoleic acid reduces high fat diet-induced liver inflammation by promoting PPAR-γ-independent M2a polarization of myeloid cells. Biochim Biophys Acta Mol Cell Biol Lipids. 2020 Oct;1865(10):158776. doi: 10.1016/j.bbalip.2020.158776. Epub 2020 Jul 30. PMID: 32738301; PMCID: PMC7487782.

[16.] Stefan N, Kantartzis K, Celebi N, Staiger H, Machann J, Schick F, Cegan A, Elcnerova M, Schleicher E, Fritsche A, Häring HU. Circulating palmitoleate strongly and independently predicts insulin sensitivity in humans. Diabetes Care. 2010 Feb;33(2):405-7. doi: 10.2337/dc09-0544. Epub 2009 Nov 4. PMID: 19889804; PMCID: PMC2809292.

[17.] Varga T, Czimmerer Z, Nagy L. PPARs are a unique set of fatty acid regulated transcription factors controlling both lipid metabolism and inflammation. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 2011;1812(8):1007-1022. doi:https://doi.org/10.1016/j.bbadis.2011.02.014

‌[18.] Yang B, Kallio HP. Fatty acid composition of lipids in sea buckthorn (Hippophaë rhamnoides L.) berries of different origins. J Agric Food Chem. 2001 Apr;49(4):1939-47. doi: 10.1021/jf001059s. PMID: 11308350.

[19.] Ye, G., Gao, H., Wang, Z. et al. PPARα and PPARγ activation attenuates total free fatty acid and triglyceride accumulation in macrophages via the inhibition of Fatp1 expression. Cell Death Dis 10, 39 (2019). https://doi.org/10.1038/s41419-018-1135-3

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