Low dose resveratrol improves cerebrovascular function in type 2 diabetes mellitus.
Progressive microvascular dysfunction in type 2 diabetes mellitus (T2DM) may impair the ability of cerebral vessels to supply blood to brain regions during local metabolic demand, thereby increasing risks of dementia. Having previously demonstrated that resveratrol can enhance vasodilator function in the systemic circulation, we hypothesised that resveratrol could similarly benefit the cerebral circulation. We aimed to determine the most efficacious dose of resveratrol to improve cerebral vasodilator responsiveness (CVR) in T2DM.



In a double-blind, placebo-controlled, balanced crossover intervention, 36 dementia-free, non-insulin dependent T2DM older adults (49-78 years old) consumed single doses of synthetic trans-resveratrol (0, 75, 150, and 300 mg) at weekly intervals. Transcranial Doppler ultrasound was used to assess CVR to a hypercapnic stimulus, both before and 45 min after treatment. CVR, measured bilaterally in the middle cerebral arteries (MCA) and posterior cerebral arteries (PCA), was expressed as the percentage change in mean blood flow velocity from baseline to the peak velocity attained during hypercapnia. Resveratrol consumption increased CVR in the MCA; mean within-individual changes for each dose from placebo were 13.8 ± 3.5% for 75 mg (P = 0.001), 8.9 ± 3.5% for 150 mg (P = 0.016), and 13.7 ± 3.3% for 300 mg (P < 0.001); only the 75 mg dose was efficacious in the PCA (13.2 ± 4.5%, P = 0.016).



Our results provide the first clinical evidence of an acute enhancement of vasodilator responsiveness in cerebral vessels following consumption of resveratrol in this population who are known to have endothelial dysfunction and sub-clinical cognitive impairment. Importantly, maximum improvement was observed with the lowest dose used.



ACTRN12614000891628 (www.anzctr.org.au).
University of Newcastle, School of Biomedical Sciences & Pharmacy, Clinical Nutrition Research Centre, University Drive, Callaghan, New South Wales 2308, Australia.
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Wong
University of Newcastle, School of Biomedical Sciences & Pharmacy, Clinical Nutrition Research Centre, University Drive, Callaghan, New South Wales 2308, Australia.
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Nealon
Swinburne University, Centre for Human Psychopharmacology, Hawthorn, Victoria 3122, Australia.
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Scholey
University of Newcastle, School of Biomedical Sciences & Pharmacy, Clinical Nutrition Research Centre, University Drive, Callaghan, New South Wales 2308, Australia. Electronic address: peter.howe@newcastle.edu.au.
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Howe
D000368:Aged; D001783:Blood Flow Velocity / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D002561:Cerebrovascular Disorders / Q000000981:diagnostic imaging / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D003071:Cognition / Q000187:drug effects; D003072:Cognition Disorders / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control / Q000523:psychology; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D003925:Diabetic Angiopathies / Q000000981:diagnostic imaging / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020768:Middle Cerebral Artery / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000503:physiopathology; D020769:Posterior Cerebral Artery / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000503:physiopathology; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage* / Q000009:adverse effects; D013997:Time Factors; D016896:Treatment Outcome; D017585:Ultrasonography, Doppler, Transcranial; D014664:Vasodilation / Q000187:drug effects*; D014739:Victoria
D013267:Stilbenes; D000077185:Resveratrol
Cerebrovascular circulation; Diabetes mellitus; Nutrition; Vasodilatation