Effects of Anthocyanin Supplementation on Serum Lipids, Glucose, Markers of Inflammation and Cognition in Adults With Increased Risk of Dementia - A Pilot Study

Anne Katrine Bergland, Hogne Soennesyn, Ingvild Dalen, Ana Rodriguez-Mateos, Rolf Kristian Berge, Lasse Melvaer Giil, Lawrence Rajendran, Richard Siow, Michele Tassotti, Alf Inge Larsen, Dag Aarsland, Anne Katrine Bergland, Hogne Soennesyn, Ingvild Dalen, Ana Rodriguez-Mateos, Rolf Kristian Berge, Lasse Melvaer Giil, Lawrence Rajendran, Richard Siow, Michele Tassotti, Alf Inge Larsen, Dag Aarsland

Abstract

Background: Anthocyanins may protect against cardiovascular related cognitive decline and dementia.

Objective: Open-label study to measure changes in serum lipids, glucose, glycosylated hemoglobin (HbA1c), and markers of inflammation after anthocyanin supplementation in people with increased risk of dementia. As a secondary endpoint we examined potential changes in a battery of cognitive test in the anthocyanin group (AG). A total of 27 individuals with mild cognitive impairment (MCI) (n = 8) or stable non-obstructive coronary artery disease (CAD) (n = 19) consumed two Medox® capsules, each containing 80 mg of natural purified anthocyanins, twice daily for 16 weeks. They provided blood samples and performed a short battery of cognitive tests. Twenty healthy normal controls (NC) (n = 20) provided blood samples, but did not receive any intervention and did not perform cognitive tests.

Results: There was a significant difference between groups for CCL-5/RANTES [regulated on activation, normal T-cell expressed and secreted (RANTES)]. In addition, total cholesterol and triglycerides were significantly increased in the AG. Improvements in memory and executive test scores were observed. No adverse effects were reported.

Conclusion: The results of this pilot study were largely inconclusive with regard to the potential protective effects of anthocyanin supplementation. However, anthocyanins were well tolerated, and compliance was high. Larger, placebo-controlled studies to explore the potential effects of anthocyanins on dementia risk are encouraged.

Clinical trial registration: www.ClinicalTrials.gov, identifier NCT02409446.

Keywords: MCI; anthocyanins; inflammation markers; lipids; mild cognitive impairment.

Figures

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FIGURE 1
Enrolment of participants. N, number.

References

    1. Appay V., Rowland-Jones S. L. (2001). RANTES: a versatile and controversial chemokine. Trends Immunol. 22 83–87. 10.1016/s1471-4906(00)01812-3
    1. Ashendorf L., Jefferson A. L., O’connor M. K., Chaisson C., Green R. C., Stern R. A. (2008). Trail making test errors in normal aging, mild cognitive impairment, and dementia. Arch. Clin. Neuropsychol. 23 129–137. 10.1016/j.acn.2007.11.005
    1. Barter P., Gotto A. M., Larosa J. C., Maroni J., Szarek M., Grundy S. M., et al. (2007). HDL cholesterol, very low levels of LDL cholesterol, and cardiovascular events. N. Engl. J. Med. 357 1301–1310. 10.1056/nejmoa064278
    1. Dénes Á, Humphreys N., Lane T. E., Grencis R., Rothwell N. (2010). Chronic systemic infection exacerbates ischemic brain damage via a CCL5 (regulated on activation, normal T-cell expressed and secreted)-mediated proinflammatory response in mice. J. Neurosci. 30 10086–10095. 10.1523/JNEUROSCI.1227-10.2010
    1. Faria A., Meireles M., Fernandes I., Santos-Buelga C., Gonzalez-Manzano S., Dueñas M., et al. (2014). Flavonoid metabolites transport across a human BBB model. Food Chem. 149 190–196. 10.1016/j.foodchem.2013.10.095
    1. Feliciano R. P., Istas G., Heiss C., Rodriguez-Mateos A. J. M. (2016). Plasma and urinary phenolic profiles after acute and repetitive intake of wild blueberry. Molecules 21 1120. 10.3390/molecules21091120
    1. Fladby T., Pålhaugen L., Selnes P., Waterloo K., Bråthen G., Hessen E., et al. (2017). Detecting at-risk alzheimer’s disease cases. J. Alzheimer’s Dis. 60 97–105.
    1. Folstein M. F., Folstein S. E., Mchugh P. R. (1975). “Mini-mental state”: a practical method for grading the cognitive state of patients for the clinician. J. Psychiatr. Res. 12 189–198.
    1. Golden C. J. (1976). Identification of brain disorders by the stroop color and word test. J. Clin. Psychol. 32 654–658. 10.1002/1097-4679(197607)32:3<654::aid-jclp2270320336>;2-z
    1. Grammas P. (2011). Neurovascular dysfunction, inflammation and endothelial activation: implications for the pathogenesis of Alzheimer’s disease. J. Neuroinflamm. 8:26. 10.1186/1742-2094-8-26
    1. Hassellund S., Flaa A., Kjeldsen S., Seljeflot I., Karlsen A., Erlund I., et al. (2013). Effects of anthocyanins on cardiovascular risk factors and inflammation in pre-hypertensive men: a double-blind randomized placebo-controlled crossover study. J. Hum. Hypertens. 27 100–106. 10.1038/jhh.2012.4
    1. Hein S., Whyte A. R., Wood E., Rodriguez-Mateos A., Williams C. M. (2019). Systematic review of the effects of blueberry on cognitive performance as we age. J. Gerontol. A Biol. Sci. Med. Sci. [Epub ahead of print]
    1. Karlsen A., Retterstøl L., Laake P., Paur I., Kjølsrud-Bøhn S., Sandvik L., et al. (2007). Anthocyanins inhibit nuclear factor-κB activation in monocytes and reduce plasma concentrations of pro-inflammatory mediators in healthy adults. J. Nutr. 137 1951–1954. 10.1093/jn/137.8.1951
    1. Kent K., Charlton K., Roodenrys S., Batterham M., Potter J., Traynor V., et al. (2015). Consumption of anthocyanin-rich cherry juice for 12 weeks improves memory and cognition in older adults with mild-to-moderate dementia. Eur. J. Nutr. 56 333–341. 10.1007/s00394-015-1083-y
    1. Krikorian R., Nash T. A., Shidler M. D., Shukitt-Hale B., Joseph J. A. (2010a). Concord grape juice supplementation improves memory function in older adults with mild cognitive impairment. Br. J. Nutr. 103 730–734. 10.1017/S0007114509992364
    1. Krikorian R., Shidler M. D., Nash T. A., Kalt W., Vinqvist-Tymchuk M. R., Shukitt-Hale B., et al. (2010b). Blueberry supplementation improves memory in older adults†. J. Agric. Food Chem. 58 3996–4000. 10.1021/jf9029332
    1. Li D., Zhang Y., Liu Y., Sun R., Xia M. (2015). Purified anthocyanin supplementation reduces dyslipidemia, enhances antioxidant capacity, and prevents insulin resistance in diabetic patients. J. Nutr. 145 742–748. 10.3945/jn.114.205674
    1. Lorenz M., Jochmann N., Von Krosigk A., Martus P., Baumann G., Stangl K., et al. (2007). Addition of milk prevents vascular protective effects of tea. Eur. Heart J. 28 219–223. 10.1093/eurheartj/ehl442
    1. Mitchell A. J., Bird V., Rizzo M., Meader N. (2010). Diagnostic validity and added value of the geriatric depression scale for depression in primary care: a meta-analysis of GDS30 and GDS15. J. Affect. Disord. 125 10–17. 10.1016/j.jad.2009.08.019
    1. Morris J. C., Heyman A., Mohs R. C., Hughes J. P., Van Belle G., Fillenbaum G., et al. (1989). The consortium to establish a registry for Alzheimer’s disease (CERAD). Part I. clinical and neuropsychological assessment of Alzheimer’s disease. Neurology 39 1159–1165.
    1. Neveu V., Perez-Jiménez J., Vos F., Crespy V., Du Chaffaut L., Mennen L., et al. (2010). Phenol-explorer: an online comprehensive database on polyphenol contents in foods. Database 2010:ba024. 10.1093/database/bap024
    1. Qin Y., Xia M., Ma J., Hao Y., Liu J., Mou H., et al. (2009). Anthocyanin supplementation improves serum LDL-and HDL-cholesterol concentrations associated with the inhibition of cholesteryl ester transfer protein in dyslipidemic subjects. Am. J. Clin. Nutr. 90 485–492. 10.3945/ajcn.2009.27814
    1. Reitan R., Wolfson D. (1985). The Halstead-Reitan Neuropsychological Test Battery: Therapy and Clinical Assessment. Tucson, AZ: Neuropsychological Press.
    1. Rodriguez-Mateos A., Istas G., Boschek L., Feliciano R. P., Mills C. E., Boby C., et al. (2019). Circulating anthocyanin metabolites mediate vascular benefits of blueberries: insights from randomized controlled trials, metabolomics, and nutrigenomics. J. Gerontol. A Biol. Sci. Med. Sci. [Epub ahead of print]
    1. Rodriguez-Mateos A., Rendeiro C., Bergillos-Meca T., Tabatabaee S., George T. W., Heiss C., et al. (2013). Intake and time dependence of blueberry flavonoid–induced improvements in vascular function: a randomized, controlled, double-blind, crossover intervention study with mechanistic insights into biological activity. Am. J. Clin. Nutr. 98 1179–1191. 10.3945/ajcn.113.066639
    1. Rodriguez-Mateos A., Feliciano R. P., Boeres A., Weber T., Dos Santos C. N., Ventura M. R., et al. (2016). Cranberry (poly) phenol metabolites correlate with improvements in vascular function: a double-blind, randomized, controlled, dose-response, crossover study. Mol. Nutr. Food Res. 60 2130–2140. 10.1002/mnfr.201600250
    1. Scarpina F., Tagini S. (2017). The stroop color and word test. Front. Psychol. 8:557. 10.3389/fpsyg.2017.00557
    1. Song F., Zhu Y., Shi Z., Tian J., Deng X., Ren J., et al. (2014). Plant food anthocyanins inhibit platelet granule secretion in hypercholesterolaemia: involving the signalling pathway of PI3K–Akt. Thromb. Haemost. 112 981–991. 10.1160/th13-12-1002
    1. Spagnuolo C., Moccia S., Russo G. L. (2017). Anti-inflammatory effects of flavonoids in neurodegenerative disorders. Eur. J. Med. Chem. 153 105–115. 10.1016/j.ejmech.2017.09.001
    1. Spencer J. P., Vafeiadou K., Williams R. J., Vauzour D. (2012). Neuroinflammation: modulation by flavonoids and mechanisms of action. Mol. Aspects Med. 33 83–97. 10.1016/j.mam.2011.10.016
    1. Stone N. J., Robinson J. G., Lichtenstein A. H., Merz C. N. B., Blum C. B., Eckel R. H., et al. (2014). 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the american college of cardiology/american heart association task force on practice guidelines. J. Am. Coll. Cardiol. 63 2889–2934.
    1. Wallace T. C., Slavin M., Frankenfeld C. L. (2016). Systematic review of anthocyanins and markers of cardiovascular disease. Nutrients 8:32. 10.3390/nu8010032
    1. Whyte A., Cheng N., Fromentin E., Williams C. J. N. (2018). A randomized, double-blinded, placebo-controlled study to compare the safety and efficacy of low dose enhanced wild blueberry powder and wild blueberry extract (ThinkBlue) in maintenance of episodic and working memory in older adults. Nutrients 10:E660. 10.3390/nu10060660
    1. World Health Organization [WHO] (1992). The ICD-10 Classification of Mental and Behavioural Disorders: Clinical Descriptions and Diagnostic Guidelines. Geneva: World Health Organization.
    1. Xia M., Ling W., Zhu H., Wang Q., Ma J., Hou M., et al. (2007). Anthocyanin prevents CD40-activated proinflammatory signaling in endothelial cells by regulating cholesterol distribution. Arterioscler. Thromb. Vasc. Biol. 27 519–524. 10.1161/01.atv.0000254672.04573.2d
    1. Yang L., Ling W., Du Z., Chen Y., Li D., Deng S., et al. (2017). Effects of anthocyanins on cardiometabolic health: a systematic review and meta-analysis of randomized controlled trials. Adv. Nutr. 8 684–693. 10.3945/an.116.014852
    1. Yilmaz G., Granger D. N. (2010). Leukocyte recruitment and ischemic brain injury. Neuromol. Med. 12 193–204. 10.1007/s12017-009-8074-1
    1. Zhong S., Sandhu A., Edirisinghe I., Burton-Freeman I., Research F. (2017). Characterization of wild blueberry polyphenols bioavailability and kinetic profile in plasma over 24-h period in human subjects. Mol. Nutr. Food Res. 61:1700405. 10.1002/mnfr.201700405
    1. Zhu Y., Xia M., Yang Y., Liu F., Li Z., Hao Y., et al. (2011). Purified anthocyanin supplementation improves endothelial function via NO-cGMP activation in hypercholesterolemic individuals. Clin. Chem. 57 1524–1533. 10.1373/clinchem.2011.167361

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