Vascular effects and safety of supplementation with shark liver oil in middle‑aged and elderly males

Hamadate,Naobumi; Matsumoto,Yoshiyuki; Seto,Kayoko; Yamamoto,Tetsuro; Yamaguchi,Hideyo; Nakagawa,Takashi; Yamamoto,Etsushi; Fukagawa,Mitsuhiko; Yazawa,Kazunaga

doi:10.3892/etm.2015.2568

Vascular effects and safety of supplementation with shark liver oil in middle‑aged and elderly males

Authors:
- Naobumi Hamadate
- Yoshiyuki Matsumoto
- Kayoko Seto
- Tetsuro Yamamoto
- Hideyo Yamaguchi
- Takashi Nakagawa
- Etsushi Yamamoto
- Mitsuhiko Fukagawa
- Kazunaga Yazawa
View Affiliations

Affiliations: Department of Research and Development, Egao Co., Ltd., Kumamoto 862-0902, Japan, Research Center, TTC Co., Ltd., Shibuya‑ku, Tokyo 113-0021, Japan, Shinyokohama Shinoharaguchi Orthopaedic Surgery/Dermatology Clinic, Yokohama, Kanagawa 222-0026, Japan, Laboratory of Nutraceuticals and Functional Foods Science, Tokyo University of Marine Science and Technology, Minato-ku, Tokyo 108-8477, Japan
Published online on: June 11, 2015 https://doi.org/10.3892/etm.2015.2568
Pages: 641-646

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Shark liver oil (SLO) has long been used as a traditional health food, with a particular benefit for vascular health, in Japan. The aim of this study was to assess the effect of dietary supplementation with SLO on arterial stiffness and peripheral microvascular function in otherwise healthy middle‑aged and older males with slightly increased arterial stiffness. A randomized, double‑blind, placebo‑controlled, parallel study design was used to assign 41 healthy males with a mean age of 59.0±4.0 years (range, 45‑69 years) to either SLO (n=21) or placebo (n=20) treatment for eight weeks. The effects on arterial stiffness and peripheral microvascular function were assessed by the cardio‑ankle vascular index (CAVI) and by measurement of hand blood flow to cutaneous tissues using a laser Doppler perfusion imaging (LDPI) technique, respectively. Although the magnitude of the changes in the CAVI value during the eight‑week intervention for the SLO group did not significantly differ from that for the placebo group, the changes in the CAVI value for the former group were significantly associated (r=0.575, P<0.01) with age. It was also found that the LDPI values at week 8 were significantly lowered (P<0.05) compared with the baseline values in the placebo group, while no change was observed in the SLO group, resulting in a significant difference in the changes between the two groups (P=0.002). Neither SLO supplementation‑related adverse side‑effects nor any abnormal changes in routine laboratory tests, including lipid profiles and anthropometric and haemodynamic parameters, were observed throughout the intervention. SLO may have the potential to safely improve vascular health in middle‑aged and elderly males.

View Figures

View References

1	Tsujimoto M: A highly unsaturated hydrocarbon in shark liver oil. Ind Eng Chem. 8:889–896. 1916. View Article : Google Scholar
2	Reddy LH and Couvreur P: Squalene: A natural triterpene for for use in disease management and therapy. Adv Drug Deliv Rev. 61:1412–1426. 2009. View Article : Google Scholar : PubMed/NCBI
3	Mottram P, Shiqe H and Nestel P: Vitamin E improves arterial compliance in middle-aged men and women. Atherosclerosis. 145:399–404. 1999. View Article : Google Scholar : PubMed/NCBI
4	Plantinga Y, Ghiadoni L, Magagna A, Giannarelli C, Franzoni F, Taddei S and Salvetti A: Supplementation with vitamins C and E improves arterial stiffness and endothelial function in essential hypertensive patients. Am J Hypertens. 20:392–397. 2007. View Article : Google Scholar : PubMed/NCBI
5	Jörneskog G, Brismar K and Fagrell B: Skin capillary circulation severely impaired in toes of patients with IDDM, with and without late diabetic complications. Diabetologia. 38:474–480. 1995. View Article : Google Scholar : PubMed/NCBI
6	Nilsson L, Apelqvist J and Edvinsson L: Effects of alpha-trinositol on peripheral circulation in diabetic patients with critical limb ischaemia. A pilot study using laser Doppler fluxmetry, transcutaneous oxygen tension measurements and dynamic capillaroscopy. Eur J Vasc Endovasc Surg. 15:331–336. 1998. View Article : Google Scholar : PubMed/NCBI
7	Collins EG, Edwin Langbein W, Orebaugh C, Bammert C, Hanson K, Reda D, Edwards LC and Littooy FN: PoleStriding exercise and vitamin E for management of peripheral vascular disease. Med Sci Sports Exerc. 35:384–393. 2003. View Article : Google Scholar : PubMed/NCBI
8	Gatzka CD, Cameron JD, Kingwell BA and Dart AM: Relation between coronary artery disease, aortic stiffness, and left ventricular stiffness in a population sample. Hypertension. 32:575–578. 1998. View Article : Google Scholar : PubMed/NCBI
9	Sutton-Tyrrell K, Najjar SS, Boudreau RM, Venkitachalam L, Kupelian V, Simonsick EM, Havlik R, Lakatta EG, Spurgeon H, Kritchevsky S, Pahor M, Bauer D and Newman A: Health ABC Study: Elevated aortic pulse wave velocity, a marker of arterial stiffness, predicts cardiovascular events in well-functioning older adults. Circulation. 111:3384–3390. 2005. View Article : Google Scholar : PubMed/NCBI
10	Vlachopoulos C, Aznaouridis K and Stefanadis C: Prediction of cardiovascular events and all-cause mortality with arterial stiffness: a systematic review and meta-analysis. J Am Coll Cardiol. 55:1318–1327. 2010. View Article : Google Scholar : PubMed/NCBI
11	Kubozono T, Miyata M, Ueyama K, Nagaki A, Otsuji Y, Kusano K, Kubozono O and Tei C: Clinical significance and reproducibility of new arterial distensibility index. Circ J. 71:89–94. 2007. View Article : Google Scholar : PubMed/NCBI
12	Takaki A, Ogawa H, Wakeyama T, Iwami T, Kimura M, Hadano Y, Matsuda S, Miyazaki Y, Matsuda T, Hiratsuka A and Matsuzaki M: Cardio-ankle vascular index is a new noninvasive parameter of arterial stiffness. Circ J. 71:1710–1714. 2007. View Article : Google Scholar : PubMed/NCBI
13	Yambe T, Yoshizawa M, Saijo Y, Yamaguchi T, Shibata M, Konno S, Nitta S and Kuwayama T: Brachio-ankle pulse wave velocity and cardio-ankle vascular index (CAVI). Biomed Pharmacother 58 Suppl. 1:S95–S98. 2004. View Article : Google Scholar
14	Shirai K, Utino J, Otsuka K and Takata M: A novel blood pressure-independent arterial wall stiffness parameter; cardio-ankle vascular index (CAVI). J Atheroscler Thromb. 13:101–107. 2006. View Article : Google Scholar : PubMed/NCBI
15	Matsui Y, Kario K, Ishikawa J, Eguchi K, Hoshide S and Shimada K: Reproducibility of arterial stiffness indices (pulse wave velocity and augmentation index) simultaneously assessed by automated pulse wave analysis and their associated risk factors in essential hypertensive patients. Hypertens Res. 27:851–857. 2004. View Article : Google Scholar : PubMed/NCBI
16	Suzuki H, Ishizuka N, Makoto M, et al: Establishment of reference values of CAVI and disease characterisitics. From Bench to Bedside: CAVI as a Novel Indicator of Vascular Function. Omori H and Saito Y: Nikkei Medical Custom Publishing, Inc.; Tokyo: pp. 34–42. 2009
17	Wådell K, Jakobsson A and Nilsson G: Laser Doppler perfusion imaging by dynamic light scattering. IEEE Trans Biomed Eng. 40:309–316. 1993. View Article : Google Scholar : PubMed/NCBI
18	Bornmyr S, Svensson H, Lilja B and Sundkvist G: Skin temperature changes and changes in skin blood flow monitored with laser Doppler flowmetry and imaging: a methodological study in normal humans. Clin Physiol. 17:71–81. 1997. View Article : Google Scholar : PubMed/NCBI
19	Okura T, Watanabe S, Kurata M, Manabe S, Koresawa M, Irita J, Enomoto D, Miyoshi K, Fukuoka T and Higaki J: Relationship between cardio-ankle vascular index (CAVI) and carotid atherosclerosis in patients with essential hypertension. Hypertens Res. 30:335–340. 2007. View Article : Google Scholar : PubMed/NCBI
20	Kadota K, Takamura N, Aoyagi K, Yamasaki H, Usa T, Nakazato M, Maeda T, Wada M, Nakashima K, Abe K, Takeshima F and Ozono Y: Availability of cardio-ankle vascular index (CAVI) as a screening tool for atherosclerosis. Circ J. 72:304–308. 2008. View Article : Google Scholar : PubMed/NCBI
21	Nakamura K, Tomaru T, Yamamura S, Miyashita Y, Shirai K and Noike H: Cardio-ankle vascular index is a candidate predictor of coronary atherosclerosis. Circ J. 72:598–604. 2008. View Article : Google Scholar : PubMed/NCBI
22	Sakane K, Miyoshi T, Doi M, Hirohata S, Kaji Y, Kamikawa S, Ogawa H, Hatanaka K, Kitawaki T, Kusachi S and Yamamoto K: Association of new arterial stiffness parameter, the cardio-ankle vascular index, with left ventricular diastolic function. J Atheroscler Thromb. 15:261–268. 2008. View Article : Google Scholar : PubMed/NCBI
23	Mirbod SM, Yoshida H, Jamail M, Miyashita K, Takeda H, Inaba R and Iwata H: Finger skin temperature and laser-Doppler finger blood flow in subjects exposed to hand-arm vibration. Ind Health. 36:171–178. 1998. View Article : Google Scholar : PubMed/NCBI
24	Hallgren B, Niklasson A, Ställberg G and Thorin H: On the occurrence of 1-O-alkylglycerols and 1-O-(2-methoxyalkyl)glycerols in human colostrum, human milk, cow's milk, sheep's milk, human red bone marrow, red cells, blood plasma and a uterine carcinoma. Acta Chem Scand B. 28:1029–1034. 1974. View Article : Google Scholar : PubMed/NCBI
25	Deniau AL, Mosset P, Pédrono F, Mitre R, LeBot D and Legrand AB: Multiple beneficial health effects of natural alkylglycerols from shark liver oil. Mar Drugs. 8:2175–2184. 2010. View Article : Google Scholar : PubMed/NCBI
26	Saint-Leger D, Bague A, Cohen E and Chivot M: A possible role for squalene in the pathogenesis of acne. I. In vitro study of squalene oxidation. Br J Dermatol. 114:535–542. 1986. View Article : Google Scholar : PubMed/NCBI
27	Kohno Y, Egawa Y, Itoh S, et al: Kinetic study of quenching reaction of singlet oxygen and scavenging reaction of free radical by squalene in n-butanol. Biochim Biophys Acta. 1256:52–56. 1995. View Article : Google Scholar : PubMed/NCBI
28	Sabeena Farvin KH, Surendraraj A and Anandan R: Protective effect of squalene on endogenous antioxidant vitamins in experimentally induced myocardial infarction in rats. Asian J Biochem. 4:133–139. 2009. View Article : Google Scholar
29	Sabeena Farvin KH, Kumar SHS, Anandan R, Mathew S, Sankar TV and Nair PGV: Supplementation of squalene attenuates experimentally induced myocardial infarction in rats. Food Chem. 105:1390–1395. 2007. View Article : Google Scholar
30	Sabeena Farvin KH, Anandan R, Kumar SH, Shiny KS, Sankar TV and Thankappan TK: Effect of squalene on tissue defense system in isoproterenol-induced myocardial infarction in rats. Pharmacol Res. 50:231–236. 2004. View Article : Google Scholar : PubMed/NCBI
31	Strandberg TE, Tilvis RS and Miettinen TA: Metabolic variables of cholesterol during squalene feeding in humans: comparison with cholestyramine treatment. J Lipid Res. 31:1637–1643. 1990.PubMed/NCBI
32	Miettinen TA and Vanhanen H: Serum concentration and metabolism of cholesterol during rapeseed oil and squalene feeding. Am J Clin Nutr. 59:356–363. 1994.PubMed/NCBI
33	Gylling H and Miettinen TA: Postabsorptive metabolism of dietary squalene. Atherosclerosis. 106:169–178. 1994. View Article : Google Scholar : PubMed/NCBI
34	Motoyama T, Kawano H, Kugiyama K, Hirashima O, Ohgushi M, Tsunoda R, Moriyama Y, Miyao Y, Yoshimura M, Ogawa H and Yasue H: Vitamin E administration improves impairment of endothelium-dependent vasodilation in patients with coronary spastic angina. J Am Coll Cardiol. 32:1672–1679. 1998. View Article : Google Scholar : PubMed/NCBI
35	Wang S, Ma AQ, Song SW, Quan QH, Zhao XF and Zheng XH: Fish oil supplementation improves large arterial elasticity in overweight hypertensive patients. Eur J Nutr. 62:1426–1431. 2008. View Article : Google Scholar
36	Fahs CA, Yan H, Ranadive S, Rossow LM, Agiovlasitis S, Wilund KR and Fernhall B: The effect of acute fish-oil supplementation on endothelial function and arterial stiffness following a high-fat meal. Appl Physiol Nutr Metab. 35:294–302. 2010. View Article : Google Scholar : PubMed/NCBI
37	Mozaffarian D and Wu JH: (n-3) fatty acids and cardiovascular health: are effects of EPA and DHA shared or complementary? J Nutr. 142:614S–625S. 2012. View Article : Google Scholar : PubMed/NCBI
38	Siasos G, Kioufis S, Maniatis K, Miliou A and Siasou Z: Effects of Ω-3 fatty acids on endothelial function, arterial wall properties, inflammatory and fibrinolytic status in smokers: a cross-over study. Int J Cardiol. 116:340–346. 2013. View Article : Google Scholar
39	Sawada M, Matsuo M, Hagihara H, Tenda N, Nagayoshi A, Okumura H, Washizuka K, Seki J and Goto T: Effect of FR194738, a potent inhibitor of squalene epoxidase on cholesterol metabolism in HepG2 cells. Eur J Pharmacol. 431:11–16. 2001. View Article : Google Scholar : PubMed/NCBI
40	Newmark HL: Squalene, olive oil, and cancer risk. Review and hypothesis. Ann NY Acad Sci. 889:193–203. 1999. View Article : Google Scholar : PubMed/NCBI
41	Smith TJ: Squalene: potential chemopreventive agent. Expert Opin Investig Drugs. 9:1841–1848. 2000. View Article : Google Scholar : PubMed/NCBI
42	Kaminura H, Koga N, Oguri K, Yoshimura H, Inoue H, Sato K and Ohkubo M: Studies on distribution, excretion and subacute toxicity of squalene in dogs. Fukuoka Igaku Zasshi. 80:269–280. 1989.(In Japanese). PubMed/NCBI
43	Sotiroudis TG and Kyrtopoulos SA: Anticarcinogenic compounds of olive oil and related biomarkers. Eur J Nutr. 47(Suppl 2): 69–72. 2008. View Article : Google Scholar : PubMed/NCBI