Highlights
- •Daily supplementation with palm-tocotrienols increased plasma tocotrienol levels.
- •Daily supplementation with palm-carotenes increased plasma carotene levels.
- •Palm-tocotrienols had no effects, superior or detrimental, on vascular function.
- •Palm-carotenes had no effects, superior or detrimental, on vascular function.
Abstract
Background and aims
In vitro, ex vivo and animal studies suggest palm-based tocotrienols and carotenes enhance vascular
function, but limited data in humans exists. The aim was to examine the effects of
palm-tocotrienols (TRF- 80) and palm-carotene (CC-60) supplementation on vascular
function and cardiovascular disease (CVD) risk factors in adults at increased risk
of impaired vascular function.
Methods
Ninety men and women (18–70 yr, 20–45 kg/m2) with type 2 diabetes, impaired fasting glucose and/or elevated waist circumference
were randomised to consume either TRF-80 (420 mg/day tocotrienol + 132 mg/day tocopherol),
CC-60 (21 mg/day carotenes) or placebo (palm olein) supplements for 8 weeks. Brachial
artery flow-mediated dilation (FMD), other physiological and circulatory markers of
vascular function, lipid profiles, glucose, insulin and inflammatory markers were
assessed pre- and post-supplementation. Pairwise comparisons were performed using
mixed effects longitudinal models (n = 87, n = 3 withdrew before study commencement).
Results
Plasma α- and β-carotene and α-, δ- and γ-tocotrienol concentrations increased in
CC-60 and TRF-80 groups, respectively, compared to placebo (mean ± SE difference in
total plasma carotene change between CC-60 and placebo: 1.5 ± 0.13 μg/ml, p < 0.0001; total plasma tocotrienol change between TRF-80 and placebo: 0.36 ± 0.05 μg/ml,
p < 0.0001). Neither FMD (treatment x time effect for CC-60 vs. placebo, p = 0.71; TRF-80 vs. placebo, p = 0.80) nor any other vascular function and CVD outcomes were affected by treatments.
Conclusions
CC-60 and TRF-80 supplementation increased bioavailability of palm-based carotenes
and tocotrienols but had no effects, superior or detrimental, on vascular function
or CVD risk factors.
Keywords
Abbreviations:
AI (augmentation index), BMI (body mass index), CTAB (citrate, theophylline, adenosine and dipyridamole), CV (coefficient of variance), CVD (cardiovascular disease), EFSA (European Food Safety Authority), eGFR (estimated global filtration rate), FID (flow-independent dilation), FMD (flow-mediated dilation), HbA1c (glycated haemoglobin), HDL-C (high density lipoprotein cholesterol), HOMA2-IR (homeostasis assessment model 2 Insulin resistance), hsCRP (high sensitivity C-reactive protein), HMG-C0A (3-hydroxy-3-methylglutaryl-coenzyme A), ICAM-1 (intercellular adhesion molecule-1), IFG (impaired fasting glucose), IMVS (Institute of Medical and Veterinary Science), IL-6 (interleukin-6), IR (insulin resistance), LDL-C (low density lipoprotein cholesterol), NOAEL (no-observed-adverse-effect level), NSAID (non-steroidal anti-inflammatory drugs), PAI-1 (plasminogen activator inhibitor 1), PWV (pulse wave velocity), SDT (suggested dietary target), T (tocopherol), T3 (tocotrienol), T2DM (type 2 diabetes mellitus), TC (total cholesterol), TG (triglycerides), TNFα (tumor necrosis factor alpha), tPA (tissue plasminogen activator), TRF (tocotrienol-rich fraction), VCAM-1 (vascular cell adhesion molecule-1), WC (waist circumference)To read this article in full you will need to make a payment
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References
- Atherosclerosis: risk factors and the vascular endothelium.Am. Heart J. 1996; 131: 379-384
- Prognostic value of flow-mediated vasodilation in brachial artery and fingertip artery for cardiovascular events: a systematic review and meta-analysis.J. Am. Heart Assoc. 2015; 4
- Tea, flavonoids, and nitric oxide-mediated vascular reactivity.J. Nutr. 2008; 138: 1554S-1560S
- Palm oil tocotrienol fractions restore endothelium dependent relaxation in aortic rings of streptozotocin-induced diabetic and spontaneously hypertensive rats.Nutr. Res. 2010; 30: 209-216
- Chemistry and biochemistry of palm oil.Prog. Lipid Res. 2000; 39: 507-558
- Palm oil-derived natural vitamin E alpha-tocotrienol in brain health and disease.J. Am. Coll. Nutr. 2010; 29: 314S-323S
- Tocotrienols, the vitamin E of the 21st century: its potential against cancer and other chronic diseases.Biochem. Pharmacol. 2010; 80: 1613-1631
- Dietary red palm oil supplementation reduces myocardial infarct size in an isolated perfused rat heart model.Lipids Health Dis. 2010; 9: 64
- Dietary red palm oil reduces ischaemia-reperfusion injury in rats fed a hypercholesterolaemic diet.Br. J. Nutr. 2007; 97: 653-660
- Vascular protective actions of natural antioxidants.in: Packer L. Traber M.G. Xin W. Natural Anti-oxidants: Molecular Mechanisms and Health Effects. AOCS Press, Champaign, IL1996: 584-594
- Modulation of vascular endothelial cell function by palm oil antioxidants.Asia Pac J. Clin. Nutr. 1997; 6: 68-71
- Carotenoids and cardiovascular risk.Curr. Pharm. Des. 2012; 18: 5577-5589
- Vascular cell adhesion molecule-1 expression and signaling during disease: regulation by reactive oxygen species and antioxidants.Antioxid. Redox Signal. 2011; 15: 1607-1638
- Vitamin E therapy beyond cancer Tocopherol versus tocotrienol.Pharmacol. Ther. 2016; 162: 152-169
- Prognostic role of flow-mediated dilation and cardiac risk factors in post-menopausal women.J. Am. Coll. Cardiol. 2008; 51: 997-1002
- Body fat distribution predicts the degree of endothelial dysfunction in uncomplicated obesity.Int. J. Obes. Relat. Metab. Disord. 1999; 23: 936-942
- Usefulness of visceral obesity (waist/hip ratio) in predicting vascular endothelial function in healthy overweight adults.Am. J. Cardiol. 2001; 88: 1264-1269
- Endothelial dysfunction in impaired fasting glycemia, impaired glucose tolerance, and type 2 diabetes mellitus.Am. J. Cardiol. 2008; 102: 497-498
- The Anti Cancer Council of Victoria FFQ: relative validity of nutrient intakes compared with weighed food records in young to middle-aged women in a study of iron supplementation.Aust. N. Z. J. Public Health. 2000; 24: 576-583
- Folic acid improves endothelial dysfunction in type 2 diabetes–an effect independent of homocysteine-lowering.Vasc. Med. 2006; 11: 101-109
- Scientific Opinion on the re-evaluation of mixed carotenes (E 160a (i)) and beta-carotene (E 160a (ii)) as a food additive.EFSA J. 2012; 10: 2593
- Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids.National Academy of Sciences, Washington DC2000
- Opinion on mixed tocopherols, tocotrienols tocopherol and tocotrienols as sours.EFSA J. 2008; 640: 1-34
- Long-term effects of weight loss with a very low carbohydrate and low fat diet on vascular function in overweight and obese patients.J. Intern Med. 2010; 267: 452-461
- SFAs do not impair endothelial function and arterial stiffness.Am. J. Clin. Nutr. 2013; 98: 677-683
- Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge.Clin. Chem. 1972; 18: 499-502
- Correct homeostasis model assessment (HOMA) evaluation uses the computer program.Diabetes Care. 1998; 21: 2191-2192
- Methodology of plasma retinol, tocopherol and carotenoid assays in cancer prevention studies.J. Nutr. Growth Cancer. 1987; 4: 19-27
- Simultaneous determination of tocotrienols, tocopherols, retinol, and major carotenoids in human plasma.Clin. Chem. 2003; 49: 2056-2066
- Analysis of tocotrienols in different sample matrixes by HPLC.in: Methods in Molecular Biology: Oxidative Sress Biomarkers and Antioxidant Protocols. vol. 186. Humana Press Inc, Totowa, NJ2002
- Flow-mediated dilation and cardiovascular risk prediction: a systematic review with meta-analysis.Int. J. Cardiol. 2013; 168: 344-351
- Nutrient Reference Values for Australia and New Zealand. Australian National Health and Medical Research Council, New Zealand Ministry of Health, Canberra, Australia2006
- Alpha-tocotrienol is the most abundant tocotrienol isomer circulated in plasma and lipoproteins after postprandial tocotrienol-rich vitamin E supplementation.Nutr. J. 2012; : 11
- Arterial compliance and vitamin E blood levels with a self emulsifying preparation of tocotrienol rich vitamin E.Arch. Pharmacal. Res. 2008; 31: 1212-1217
- The effect of natural carotenoid (palm fruit carotene) intake on skin lipid peroxidation in hairless mice.J. Nutr. Sci. Vitaminol. (Tokyo). 1994; 40: 303-314
- Pharmacokinetics and bioavailability of alpha-, gamma- and delta-tocotrienols under different food status.J. Pharm. Pharmacol. 2001; 53: 67-71
- Supplementation of a gamma-tocopherol-rich mixture of tocopherols in healthy men protects against vascular endothelial dysfunction induced by postprandial hyperglycemia.J. Nutr. Biochem. 2013; 24: 196-203
- Acute effects of oats and vitamin E on endothelial responses to ingested fat.Am. J. Prev. Med. 2001; 20: 124-129
- Bioavailability of tocotrienols: evidence in human studies.Nutr. Metabol. 2014; : 11
- Clinical pharmacokinetics of antioxidants and their impact on systemic oxidative stress.Clin. Pharmacokinet. 2003; 42: 437-459
- Assessment of flow-mediated vasodilatation (FMD) of the brachial artery: effects of technical aspects of the FMD measurement on the FMD response.Eur. Heart J. 2005; 26: 363-368
- Effects of weight loss intervention on erectile function in older men with type 2 diabetes in the Look AHEAD trial.J. Sex. Med. 2010; 7: 156-165
- Antioxidant vitamin supplementation reduces arterial stiffness in adults: a systematic review and meta-analysis of randomized controlled trials.J. Nutr. 2014; 144: 1594-1602
- Pharmacological potential of tocotrienols: a review.Nutr. Metabol. 2014; : 11
- Carotenoids, inflammation, and oxidative stress–implications of cellular signaling pathways and relation to chronic disease prevention.Nutr. Res. 2014; 34: 907-929
- Vitamin E tocotrienol supplementation improves lipid profiles in chronic hemodialysis patients.Vasc. Health Risk Manag. 2013; 9: 747-761
- Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease.N. Engl. J. Med. 1996; 334: 1150-1155
- The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. The Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group.N. Engl. J. Med. 1994; 330: 1029-1035
- Changes in cholesterol and triglyceride concentrations in the vanguard population of the carotene and retinol efficacy trial (CARET).Eur. J. Clin. Nutr. 2005; 59: 1173-1180
- Metabolomic profile of response to supplementation with beta-carotene in the alpha-tocopherol, beta-carotene Cancer prevention study.Am. J. Clin. Nutr. 2013; 98: 488-493
- Dietary intake of carotenoids and their antioxidant and anti-inflammatory effects in cardiovascular care.Mediat. Inflamm. 2013; 2013: 782137
- Oxidative stress, inflammation, endothelial dysfunction and incidence of type 2 diabetes.Cardiovasc Diabetol. 2016; 15: 51
- The therapeutic impacts of tocotrienols in type 2 diabetic patients with hyperlipidemia.Atherosclerosis. 2005; 182: 367-374
- Response of hypercholesterolemic subjects to administration of tocotrienols.Lipids. 1995; 30: 1171-1177
- Dose-dependent suppression of serum cholesterol by tocotrienol-rich fraction (TRF25) of rice bran in hypercholesterolemic humans.Atherosclerosis. 2002; 161: 199-207
- Tocotrienols regulate cholesterol production in mammalian cells by post-transcriptional suppression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase.J. Biol. Chem. 1993; 268: 11230-11238
- Obesity and Overweight: Fact Sheet No 311.2015
Article info
Publication history
Published online: October 13, 2016
Accepted:
October 13,
2016
Received in revised form:
September 29,
2016
Received:
July 22,
2016
Identification
Copyright
© 2016 Elsevier Ireland Ltd. All rights reserved.
