Macolipin (Shark Extracted Lipid)

Macolipin is an unique Shark Extracted Lipid. It has strong angiogenesis inhibitory properties which are valuable for inhibiting tumour development and metastasis in cancers. It is also a factor in the pathogenesis and progression of all angiogenesis related disorders including metabolic syndrome, psoriasis, rheumatoid arthritis, macular degeneration, diabetic retinopathy and age related skin disorders. Angiogenesis means the birth of new blood vessels and, while being an essential function in the normal development and physiology of the body, when related to cancer and other disease states it needs to be inhibited. The following excerpt from an abstract, with added explanatory notes, describes experimental evidence for the effectiveness of Macolipin in inhibiting angiogenesis.

This Shark Extracted Lipid is particularly potent in anti-angiogenesis activity. In laboratory experiments the preparation of Shark Extracted Lipid (Macolipin) which is rich in polyunsaturated fatty acids (notably docosahexaenoic acid), produced a 50% inhibition of angiogenesis at only 5µg/ml. When administered orally in vivo Macolipin elicited a 50% reduction in angiogenesis at 17mg/kg body weight. Olive oil was shown to have no inhibitory effect in the aortic ring or the in vivo models. However, Macolipin, when combined with olive oil (1:9) was twice as potent in the in vitro system.

The experiments indicate that this combination can negate the stimulatory effects of factors such as VEGF, FGF-2 and TGF-β (These are growth factors that stimulate the connection of tumours to the major blood vessels thus allowing the tumour to grow and to metastasise). They also suggest that Macolipin/Olive oil (1:9) mixture is a potent orally-active natural product that has significant anti-angiogenic effects. The anti-angiogenesis functionality of Macolipin is through the inhibition of binding of VEGF and its receptors (VEGFR-2 and VEGFR-1), and the inhibition of VEGF receptor tyrosine phosphorylation in the VEGF receptor signal transduction pathway. (In simple, very generalised, terms this means that inhibiting the growth factors from attaching to their attachment sites on the blood vessels the next processes needed to allow the signal to start angiogenesis are prevented)

The experimental and in vivo studies conducted on Macolipin, a unique lipid extract derived from the flesh of certain species of shark substances suggest that the product has value as a natural, orally administered anti-angiogenic ingredient. Macolipin has been subjected to safety studies and shown to be non toxic and non teratogenic (free from adverse effects on foetal development in pregnancy) at the Tama Institute, Japan Food Research Laboratories.

1. Lan Yuan; Mayumi Yoshida; Paul F. Davis. Inhibition of Pro-Angiogenic Factors by a Lipid-Rich Shark Extract. Journal of Medicinal Food. Fall 2006, 9(3): 300-306.
2. Lan Yuan, In-Sook Ahn, Paul F. Davis. Inhibition of Tyrosine Phosphorylation of Vascular Endothelial Growth Factor Receptors in Human Umbilical Vein Endothelial Cells: A Potent Anti-Angiogenic Lipid-Rich Extract from Shark. Journal of Medicinal Food. December 2007, 10(4): 657-661
3. Risau W. Mechanisms of angiogenesis. Nature 1997;386:671-674.
4. Ferrara N. Role of vascular endothelial growth factor in the regulation of angiogenesis. Kidney Int. 1999 Sep;56(3):794-814.
5. de Vries C, Escobedo JA, Ueno H, Houck K, Ferrara N, Williams LT. The fms-like tyrosine kinase, a receptor for vascular endothelial growth factor. Science. 1992 Feb 21;255(5047):989-91.
6. Terman BI, Dougher-Vermazen M, Carrion ME, Dimitrov D, Armellino DC, Gospodarowicz D, Bohlen P. Identification of the KDR tyrosine kinase as a receptor for vascular endothelial cell growth factor. Biochem Biophys Res Commun. 1992 Sep 30;187(3):1579-86.
7. Waltenberger J, Claesson-Welsh L, Siegbahn A, Shibuya M, Heldin CH. Different signal transduction properties of KDR and Flt1, two receptors for vascular endothelial growth factor. J Biol Chem. 1994 Oct 28;269(43):26988-95.
8. McMahon G. VEGF receptor signalling in tumor angiogenesis. Oncologist. 2000;5 Suppl 1:3-10.
9. Davis PF, Yi H, Furneaux RH, Johnston PS, Ru ger BM, Slim GC. Inhibition of angiogenesis by oral ingestion of powdered shark cartilage in a rat model. Microvasc Res 10/1997;54(2):178-182.
10. Soker S, Gollamudi-Payne S, Fidder H, Charmahelli H, Klagsburn M. Inhibition of Vascular Endothelial Growth Factor (VEGF)-induced Endothelial CellProliferation by a Peptide Corresponding to the Exon 7-Encoded Domain of VEGF 165. J Biol Chem 1997; 272:31582-31588.
11. Brekken RA, Overholser JP, Stastny VA, Waltenberger J, Minna JD, Thorpe PE. Selective inhibition of vascular endothelial growth factor (VEGF) receptor 2 (KDR/Flk-1) activity by a monoclonal anti-VEGF antibody blocks tumor growth in mice. Cancer Res. 2000 Sep 15;60(18):5117-24.
12. Zachary I. VEGF signalling: integration and multi-tasking in endothelial cell biology. Biochem Soc Trans. 2003 Dec;31(Pt 6):1171-7.
13. Pages G, Milanini J, Richard DE, Berra E, Gothie E, Vinals F, Pouyssegur J. Signaling angiogenesis via p42/p44 MAP kinase cascade. Ann N Y Acad Sci. 2000 May;902:187-200.
14. Abedi H, Zachary I. Vascular endothelial growth factor stimulates tyrosine phosphorylation and recruitment to new focal adhesions of focal adhesion kinase and paxillin in endothelial cells. J Biol Chem. 1997 Jun 13;272(24):15442-51.
15. Takahashi T, Shibuya M. The 230 kDa mature form of KDR/Flk- 1 (VEGF receptor-2) activates the PLC-gamma pathway and partially induces mitotic signals in NIH3T3 fibroblasts. Oncogene. 1997 May 1;14(17):2079-89.
16. Esser S, Lampugnani MG, Corada M, Dejana E, Risau W. Vascular endothelial growth factor induces VE-cadherin tyrosine phosphorylation in endothelial cells. J Cell Sci. 1998 Jul;111 ( Pt 13):1853-65.
17. Barr MP, Byrne AM, Duffy AM, Condron CM, Devocelle M, Harriott P, Bouchier-Hayes DJ, Harmey JH. A peptide corresponding to the neuropilin-1-binding site on VEGF165 induces apoptosis of neuropilin-1-expressing breast tumour cells. Br J Cancer. 2005 Jan 31;92(2):328-33.
18. Expression of vascular endothelial growth factor, its receptor, and other angiogenic factors in human breast cancer. Cancer Res. 1996 May 1;56(9):2013-6.
19. Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983 Dec 16;65(1-2):55-63.