Advertisement

The journal of nutrition, health & aging

, Volume 22, Issue 9, pp 1092–1098 | Cite as

Markers of Hypoxia and Oxidative Stress in Aging Volunteers Ingesting Lycosomal Formulation of Dark Chocolate Containing Astaxanthin

  • Ivan M. Petyaev
  • V. A. Klochkov
  • N. E. Chalyk
  • D. V. Pristensky
  • M. P. Chernyshova
  • N. H Kyle
  • Y. K. Bashmakov
Article

Abstract

Objective

To determine if ingestion of lycosome-formulated dark chocolate (DC) containing astaxanthin (ASTX) improves bioavailability of ASTX and affects markers of hypoxia and oxidative stress in aging individuals.

Design

Randomized, blinded, four-arm, prospective study.

Settings

Lycotec Ltd, Cambridge, United Kingdom and Institute of Cardiology, Saratov, Russian Federation.

Participants

32 healthy individuals aged 60–70 years with confirmed signs of oxidative stress (increased serum levels of oxidized LDL and malonic dialdehyde) randomized into four study groups (8 volunteers each).

Intervention

Volunteers of first group were given orally 10 gr of dark chocolate (DC). Individuals from the second group received 7 mg of astaxanthin (ASTX). Third group of volunteers was supplemented with 10 gr of DC and 7 mg of ASTX ingested simultaneously as two separate formulations. Last group of the individuals was given 10 gr of a lycosomal formulation of DC containing 7 mg of co-crystalized ASTX (L-DC-ASTX), a newly developed highly bioavailable nutraceutical composition of DC containing 2 groups of antioxidants (cocoa flavanols and ASTX). All formulations were given orally, once daily for a month.

Measurements

Serum ASTX was measured by high-performance liquid chromatography. Nitric oxide, malonic dialdehyde and oxidized LDL were quantified spectrophotometrically. Oxygenation parameters were evaluated by near-infrared spectroscopy.

Results

One month ingestion of singular formulation of ASTX lead to a 20 fold buildup in serum ASTX level whereas the 4 week ingestion of L-DC-ASTX formulation was accompanied by more prominent accumulation of ASTX in serum (a 40 fold increase over the basal values) at the same daily dose of ASTX. Both antioxidants taken separately decreased serum levels of oxidized LDL and malonic dialdehyde. However effect of L-DC-ASTX formulation was more prominent. ASTX ingested alone caused a borderline increase (p=0.054) in serum nitric oxide (NO) levels, whereas DC ingestion lead to small but statistically significant increase in serum NO concentration. Higher values of NO level were seen after co-ingestion of DC and ASTX, especially in case of L-DC-ASTX formulation suggesting additive/synergistic effects of DC and ASTX on nitric oxide production. These changes were in agreement with the increase in plasma oxygen transport and tissue oxygen saturation seen in the volunteers supplemented with L-DC-ASTX formulation.

Conclusion

The nutraceutical formulation of DC and ASTX with an enhanced bioavailability of ASTX can be efficiently used for the correction of oxidative status in aging individuals.

Key words

Dark chocolate astaxanthin oxidized LDL nitric oxide 

References

  1. 1.
    M. D. Shardell, D. E. Alley, G. E. Hicks et al., “Low-serum carotenoid concentrations and carotenoid interactions predict mortality in US adults: the Third National Health and Nutrition Examination Survey,” Nutrition Research, vol. 31, no. 3, pp. 178–189, 2011.CrossRefPubMedGoogle Scholar
  2. 2.
    Y. Ito, M. Kurata, K. Suzuki, N. Hamajima, H. Hishida, and K. Aoki, “Cardiovascular disease mortality and serum carotenoid levels: a Japanese population-based follow-up study,” Journal of Epidemiology, vol. 16, no. 4, pp. 154–160, 2006.CrossRefPubMedGoogle Scholar
  3. 3.
    X. Li and J. Xu, “Dietary and circulating lycopene and stroke risk: a metaanalysis of prospective studies,” Scientific Reports, vol. 4, p. 5031, 2014.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    M. S. Donaldson, “A carotenoid health index based on plasma carotenoids and health outcomes,” Nutrients, vol. 3, no. 12, pp. 1003–1022, 2011.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Petyaev IM. Lycopene Deficiency in Ageing and Cardiovascular Disease. Oxid Med Cell Longev. 2016;2016:3218605.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Bahonar A, Saadatnia M, Khorvash F, Maracy M, Khosravi A. Carotenoids as Potential Antioxidant Agents in Stroke Prevention: A Systematic Review. Int J Prev Med. 2017 Sep 14;8:70.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Henríquez V, Escobar C, Galarza J, Gimpel J. Carotenoids in Microalgae. Subcell Biochem. 2016;79:219–37.CrossRefPubMedGoogle Scholar
  8. 8.
    Alcaíno J, Baeza M, Cifuentes V. Carotenoid Distribution in Nature. Subcell Biochem. 2016;79:3–33.CrossRefPubMedGoogle Scholar
  9. 9.
    Visioli F, Artaria C. Astaxanthin in cardiovascular health and disease: mechanisms of action, therapeutic merits, and knowledge gaps. Food Funct. 2017 Jan 25;8(1):39–63.CrossRefPubMedGoogle Scholar
  10. 10.
    Gammone MA, Riccioni G, D’Orazio N. Marine Carotenoids against Oxidative Stress: Effects on Human Health. Mar Drugs. 2015 Sep 30;13(10):6226–46.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Kang H, Kim H. Astaxanthin and β-carotene in Helicobacter pylori-induced Gastric Inflammation: A Mini-review on Action Mechanisms. J Cancer Prev. 2017 Jun;22(2):57–61.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Kitade H, Chen G, Ni Y, Ota T. Nonalcoholic Fatty Liver Disease and Insulin Resistance: New Insights and Potential New Treatments. Nutrients. 2017 Apr 14;9(4).Google Scholar
  13. 13.
    Bonet ML, Canas JA, Ribot J, Palou A. Carotenoids in Adipose Tissue Biology and Obesity. Subcell Biochem. 2016;79:377–414.CrossRefPubMedGoogle Scholar
  14. 14.
    Fassett RG, Coombes JS. Astaxanthin, oxidative stress, inflammation and cardiovascular disease. Future Cardiol. 2009 Jul;5(4):333–42.CrossRefPubMedGoogle Scholar
  15. 15.
    Anunciato TP, da Rocha Filho PA. Carotenoids and polyphenols in nutricosmetics, nutraceuticals, and cosmeceuticals. J Cosmet Dermatol. 2012 Mar;11(1):51–4.CrossRefPubMedGoogle Scholar
  16. 16.
    Chew BP, Park JS. Carotenoid action on the immune response. J Nutr. 2004 Jan;134(1):257S–261SCrossRefPubMedGoogle Scholar
  17. 17.
    Jackson H, Braun CL, Ernst H. The chemistry of novel xanthophyll carotenoids. Am J Cardiol. 2008 May 22;101(10A):50D–57D.CrossRefPubMedGoogle Scholar
  18. 18.
    Polyakov NE, Magyar A, Kispert LD. Photochemical and optical properties of watersoluble xanthophyll antioxidants: aggregation vs complexation. J Phys Chem B. 2013 Sep 5;117(35):10173–82CrossRefPubMedGoogle Scholar
  19. 19.
    Begum H, Yusoff FM, Banerjee S, Khatoon H, Shariff M. Availability and Utilization of Pigments from Microalgae. Crit Rev Food Sci Nutr. 2016 Oct 2;56(13):2209–22.CrossRefPubMedGoogle Scholar
  20. 20.
    Anarjan N, Nehdi IA, Sbihi HM, Al-Resayes SI, Malmiri HJ, Tan CP. Preparation of astaxanthin nanodispersions using gelatin-based stabilizer systems. Molecules. 2014 Sep 10;19(9):14257–65.CrossRefPubMedGoogle Scholar
  21. 21.
    Polyakov NE, Kispert LD. Water soluble biocompatible vesicles based on polysaccharides and oligosaccharides inclusion complexes for carotenoid delivery. Carbohydr Polym. 2015 Sep 5;128:207–19.CrossRefPubMedGoogle Scholar
  22. 22.
    Petyaev IM. Lycosome Technology: Advances and Perspectives. American Journal of Food Science and Nutrition. 2016, Vol. 3, No. 1, pp. 18–23.Google Scholar
  23. 23.
    Petyaev I. 2012. Carotenoid particles and uses thereof. Patent WO 2012104576 A2. Aug 9, 2012.Google Scholar
  24. 24.
    Petyaev IM. Improvement of hepatic bioavailability as a new step for the future of statin. Arch Med Sci. 2015 Apr 25;11(2):406–10.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Petyaev IM, Dovgalevsky PY, Chalyk NE, Klochkov V, Kyle NH. Reduction in blood pressure and serum lipids by lycosome formulation of dark chocolate and lycopene in prehypertension. Food Sci Nutr. 2014 Nov;2(6):744–50.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Bashmakov YK, Assaad-Khalil SH, Abou Seif M, Udumyan R, Megallaa M, Rohoma KH, Zeitoun M, Petyaev IM. Resveratrol promotes foot ulcer size reduction in type 2 diabetes patients. ISRN Endocrinol. 2014 Feb 20;2014:816307.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Petyaev IM, Dovgalevsky PY, Klochkov VA, Chalyk NE, Kyle N. Whey protein lycosome formulation improves vascular functions and plasma lipids with reduction of markers of inflammation and oxidative stress in prehypertension. ScientificWorldJournal. 2012;2012:269476.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Petyaev IM. Lycopene Deficiency in Ageing and Cardiovascular Disease. Oxid Med Cell Longev. 2016;2016:3218605.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Miyazawa T, Nakagawa K, Kimura F, Satoh A, Miyazawa T. Plasma carotenoid concentrations before and after supplementation with astaxanthin in middle-aged and senior subjects. Biosci Biotechnol Biochem. 2011;75(9):1856–8.CrossRefPubMedGoogle Scholar
  30. 30.
    Moore K, Roberts LJ. Measurement of lipid peroxidation. Free Radic Res. 1998 Jun;28(6):659–71.CrossRefPubMedGoogle Scholar
  31. 31.
    Petyaev I, Mitchinson MMJ, Hunt JV, Coussons PJ. Superoxide dismutase activity of antibodies purified from the human arteries andatherosclerotic lesions. Biochemical Society Transactions. 1998;26(1):p. S43.CrossRefPubMedGoogle Scholar
  32. 32.
    Petyaev IM, Coussons PJ. Superoxide Dismutase: Recent Advances and Clinical Applications. Paris, France: Editions Mel; 1999. Superoxide dismutase activity of antibodies purified from human atherosclerotic lesions; pp. 51–54.Google Scholar
  33. 33.
    Mao X, Gu C, Chen D, Yu B, He J. Oxidative stress-induced diseases and tea polyphenols. Oncotarget. 2017 Sep 14;8(46):81649–1661.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Sundar IK, Sellix MT, Rahman I. Redox regulation of circadian molecular clock in chronic airway diseases. Free Radic Biol Med. 2017 Oct 31. pii: S0891-5849(17)31165-6.Google Scholar
  35. 35.
    Nakamura T, Lipton SA. SNO᾿Storms Compromise Protein Activity and Mitochondrial Metabolism in Neurodegenerative Disorders. Trends Endocrinol Metab. 2017 Oct 30. pii: S1043-2760(17)30134-0.Google Scholar
  36. 36.
    Espín JC, González-Sarrías A, Tomás-Barberán FA. The gut microbiota: A key factor in the therapeutic effects of (poly)phenols. Biochem Pharmacol. 2017 Sep 1;139:82–93.CrossRefPubMedGoogle Scholar
  37. 37.
    Petyaev IM, Bashmakov YK. Dark Chocolate: Opportunity for an Alliance between Medical Science and the Food Industry? Front Nutr. 2017 Sep 26;4:43CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Serdi and Springer-Verlag France SAS, part of Springer Nature 2018

Authors and Affiliations

  • Ivan M. Petyaev
    • 1
  • V. A. Klochkov
    • 2
  • N. E. Chalyk
    • 2
  • D. V. Pristensky
    • 1
  • M. P. Chernyshova
    • 1
  • N. H Kyle
    • 1
  • Y. K. Bashmakov
    • 1
  1. 1.Lycotec Ltd, Granta Park CampusCambridgeUK
  2. 2.Institute of CardiologySaratovRussia

Personalised recommendations