Supplementation with seabuckthorn oil augmented in 16:1n-7t increases serum trans-palmitoleic acid in metabolically healthy adults: a randomized crossover dose-escalation study

Authors: HUANG, NEIL - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; MATTHAN, NIRUPA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; GALLUCCIO, JEAN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; SHI, PEILIN - Tufts University; LICHTENSTEIN, ALICE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; MOZAFFARIAN, DARIUSH - Tufts University

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/24/2020
Publication Date: 3/6/2020
Citation: Huang, N.K., Matthan, N.R., Galluccio, J.M., Shi, P., Lichtenstein, A.H., Mozaffarian, D. 2020. Supplementation with seabuckthorn oil augmented in 16:1n-7t increases serum trans-palmitoleic acid in metabolically healthy adults: a randomized crossover dose-escalation study. Journal of Nutrition. https://doi.org/10.1093/jn/nxaa060.
DOI: https://doi.org/10.1093/jn/nxaa060

Interpretive Summary: Individual fatty acids may have unique beneficial metabolic effects. In this regard of current interest are two monounsaturated fatty acids, cis palmitoleic acid and trans palmitoleic acid. In animal studies and human observational studies they have been associated with beneficial effects on cardiometablic risk factors. Unknown is whether supplementation with cis palmitoleic acid and trans palmitoleic acid increases circulating levels. This issues is critical if the in vivo effect of these two fatty acids can be directly evaluated in humans. To answer this question we conducted a randomized, double blind, 22-week, cross-over dose-escalation trial to evaluate the effect oral supplementation with cis palmitoleic acid and trans palmitoleic acid on serum phospholipid fatty acid (PLFA) composition. Subjects (7 females and 6 males; age 48 +/- 16 years, BMI 30.4 +/- 3.7 kg/m^2) were provided supplements composed of oils enriched in trans palmitoleic acid (120, 240, and 480 mg/day) or cis palmitoleic acid (380, 760, and 1520 mg/day) for 3 week periods each. We found compared to baseline, trans palmitoleic acid supplementation increased its corresponding PLFA by 27% at the highest dose. Cis palmitoleic acid increased its corresponding PLFA by 22% at the highest dose. No significant effects of either supplement were identified on blood glucose, insulin, lipids, or other clinical measures. These data indicate that supplementation with cis palmitoleic acid and trans palmitoleic acid, as a trend across doses, moderately increased levels of their corresponding PLFA, supporting the use of supplementation with these fatty acids to test potential clinical effects in humans.

Technical Abstract: Background: Cis palmitoleic acid (9-hexadecenoic acid; 16:1n-7c), a lipokine, improves insulin sensitivity, inflammation, and lipoprotein profiles in animal models; while trans palmitoleic acid (16:1n-7t) is associated with lower incidence of type 2 diabetes. The dose-response of cis and trans supplements on blood levels in humans has not been evaluated. Objective: To determine dose-response effects of oral supplementation with 16:1n-7c and 16:1n-7t on serum phospholipid fatty acid (PLFA) composition. Methods: Thirteen participants (7 females and 6 males; age 48 +/- 16 years, BMI 30.4 +/- 3.7 kg/m^2) participated in a randomized, double blind, 22-week, cross-over dose-escalation trial of oils enriched in 16:1n-7t (120, 240, and 480 mg/day) and 16:1n-7c (380, 760, and 1520 mg/day). At the end of each dose period (3 weeks) fasting blood samples were collected to determine PLFA as percent of fatty acids. Safety measures included blood glucose, insulin, lipids, and additional clinical chemistries. Dose and carryover effects were assessed using a mixed-effect repeated measures model; with trends across doses evaluated using linear regression. Results: Compared to baseline, 16:1n-7t supplementation increased PLFA 16:1n-7t by 26.6% at the highest dose (P-trend=0.0081). Supplementation with 16:1n-7c increased its corresponding PLFA by 22.4% at the highest dose (P-trend=0.0199). No significant effects of either supplement were identified on blood glucose, insulin, lipids, or other clinical measures, although this dosing study was not powered to detect such effects. No carryover effects or adverse effects were observed. Conclusions: Dietary supplementation with 16:1n-7t and 16:1n-7c as a trend across doses, moderately increased levels of their corresponding PLFA, supporting the use of supplementation with these fatty acids to test potential clinical effects in humans.