Compositions and methods comprising C16:1n7-palmitoleate
One embodiment described herein is related to methods and compositions, such as nutraceutical formulations and dietary supplements, comprising C16:1n7-palmitoleate or derivatives thereof. The methods and compositions comprising C16:1n7-palmitoleate, or derivatives thereof, safely and effectively prevent or mitigate manifestations of cardiovascular disease, including coronary artery disease and the accumulation of cholesterol or lipid deposits in the blood vessels of a subject.
1. A method for treating a cardiovascular disease or condition in a subject in need thereof comprising administering to the subject an effective amount of a composition comprising a C16:1n7-palmitoleate derivative, a palmitate derivative and a C18:1n7-vaccenoate derivative,
wherein the composition has a ratio of the C16:1n7-palmitoleate derivative to the C18:1n7-vaccenoate derivative of 1.1:1 to 100:1; and
wherein each C16:1n7-palmitoleate derivative, palmitate derivative, and C18:1n7-vaccenoate derivative is independently a free acid, pharmaceutically acceptable salt, (C 1 -C 4 )alkyl ester, monoglyceride, diglyceride, triglyceride, or a combination of any two or more thereof, and wherein administration of the composition results in about a 5% increase in HDL after 30 days compared to that observed prior to administration.
2. The method of claim 1 , further comprising reducing the deposition of cholesterol in a blood vessel in the subject.
3. The method of claim 2 , wherein the lumen diameter of at least one blood vessel in the subject is increased by at least 10%.
4. The method of claim 1 , further comprising reducing a cholesterol-associated lesion in a blood vessel in the subject.
5. The method of claim 1 , further comprising increasing the ratio of high-density lipoprotein (HDL) relative to low-density lipoprotein (LDL) in the blood serum of the subject.
6. The method of claim 1 , further comprising increasing the ratio of apolipoprotein A1 (Apo-A1) relative to apolipoprotein B (Apo-B) in the blood serum of the subject.
7. The method of claim 1 , further comprising reducing blood pressure in the subject, wherein the subject exhibits at least a 10 mmHg or 20 mmHg reduction in systolic blood pressure.
8. The method of claim 1 , further comprising reducing stenosis in the subject.
9. The method of claim 1 , further comprising reducing restenosis in the subject following angioplasty.
10. The method of claim 1 , wherein the subject exhibits one or more of the following outcomes: (a) reduced triglyceride levels compared to baseline; (b) reduced Apo B levels compared to baseline; (c) increased HDL-C levels compared to baseline; (d) no increase in LDL-C levels compared to baseline; (e) a reduction in LDL-C levels compared to baseline; (f) a reduction in non-HDL-C levels compared to baseline; (g) a reduction in vLDL levels compared to baseline; (h) an increase in apo A-1 levels compared to baseline; (i) an increase in apo A-1/apo B ratio compared to baseline; (j) a reduction in lipoprotein A levels compared to baseline; (k) a reduction in LDL particle number compared to baseline; (l) an increase in LDL size compared to baseline; (m) a reduction in remnant-like particle cholesterol compared to baseline; (n) a reduction in oxidized LDL compared to baseline; (o) no change or a reduction in fasting plasma glucose (FPG) compared to baseline; (p) a reduction in hemoglobin A 1c (HbA 1c ) compared to baseline; (q) a reduction in homeostasis model insulin resistance compared to baseline; (r) a reduction in lipoprotein associated phospholipase A2 compared to baseline; (s) a reduction in intracellular adhesion molecule-1 compared to baseline; (t) a reduction in interleukin-6 compared to baseline; (u) a reduction in plasminogen activator inhibitor-1 compared to baseline; (v) a reduction in high sensitivity C-reactive protein (hsCRP) compared to baseline; (w) an increase in serum or plasma C16:1n7-palmitoleate compared to baseline; (x) an increase in red blood cell (RBC) membrane C16:1n7-palmitoleate compared to baseline; and/or (y) a reduction or increase in one or more of serum phospholipid and/or red blood cell content of palmitic acid (PA), stearidonic acid (SA) or oleic acid (OA) compared to baseline.
11. The method of claim 1 , further comprising the administration of a medication selected from the group consisting of an angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, beta-blocker, diuretic, vasodilator, α-blocker, calcium channel blocker, a HMG-CoA reductase inhibitor, a fibrate, a bile acid sequestrant, gemfibrozil, ezetimibe therapy, and probucol.
12. The method of claim 1 , comprising at least about 20 wt %, about 35 wt %, about 50 wt %, or about 90 wt % of the C16:1n7-palmitoleate derivative.
13. The method of claim 1 , wherein the ratio of the C16:1n7-palmitoleate derivative to the palmitate derivative is about 1.1:1 to about 100:1.
14. The method of claim 1 , wherein the C16:1n7-palmitoleate derivative is a cis-C16:1n7-palmitoleate derivative.
15. The method of claim 1 , wherein the C16:1n7-palmitoleate derivative comprises a C16:1n7-palmitoleate moiety that is obtained from fish.
16. The method of claim 15 , wherein the fish is selected from one or more of anchovies, menhaden, pollock, herring, cod, salmon, smelt, tuna, mackerel and krill.
17. The method of claim 1 , wherein the subject harbors a mutation in the Apo E gene.
18. A method for treating a cardiovascular disease or condition in a subject in need thereof comprising administering to the subject an effective amount of a composition comprising a C16:1n7-palmitoleate derivative, a palmitate derivative, an oleate derivative, and a C18:1n7-vaccenoate derivative,
wherein the composition has a ratio of the C16:1n7-palmitoleate derivative to the C18:1n7-vaccenoate derivative of 1.1:1 to 100:1;
wherein the composition has a ratio of the C16:1n7-palmitoleate derivative to the oleate derivative of about 6:1 to about 100:1; and
wherein each C16:1n7-palmitoleate derivative, palmitate derivative, oleate derivative and C18:1n7-vaccenoate derivative is independently a free acid, pharmaceutically acceptable salt, (C 1 -C 4 )alkyl ester, monoglyceride, diglyceride, triglyceride, or a combination of any two or more thereof, and wherein administration of the composition results in about a 5% increase in HDL after 30 days compared to that observed prior to administration.
19. The method of claim 18 , wherein the ratio of the C16:1n7-palmitoleate derivative to the oleate derivative is about 10:1 to about 20:1, about 20:1 to about 50:1 or about 50:1 to about 100:1.