A double-blind, randomized, crossover trial protocol of whole hemp seed protein and hemp seed protein hydrolysate consumption for hypertension

Maryam Samsamikor, Dylan Mackay, Rebecca C Mollard, Rotimi E Aluko, Maryam Samsamikor, Dylan Mackay, Rebecca C Mollard, Rotimi E Aluko

Abstract

Background: Primary hypertension accounts for almost 95% of all cases of high blood pressure and is a major modifiable risk factor for cardiovascular diseases. Lifestyle interventions have been shown to prevent hypertension. One of the prominent potential therapeutic lifestyle strategies to prevent or manage hypertension is increasing dietary protein as a macronutrient or as bioactive peptides. An emerging plant-based protein source that may have anti-hypertensive properties is hemp seed.

Methods/design: A randomized, double-blind, crossover clinical trial will be conducted on 35 hypertensive participants aged 18-75 years, with a BMI between 18.5 and 40 kg/m2, systolic blood pressure (SBP) between 130 and 160 mmHg and diastolic blood pressure (DBP) ≤ 110 mmHg. The trial will be conducted for a period of 22 weeks and will consist of three treatment periods of 6 weeks, separated by 2-week washout periods. The treatments will be consumed twice a day and consist of 25 g casein, hemp seed protein (HSP), or HSP plus HSP hydrolysate (HSP+). The primary outcome of this trial is 24-h SBP, measured on the first day of first phase and the last day of each phase. Office-measured blood pressure, pulse-wave velocity and augmentation index and anthropometrics will be determined at the first and last days of each period. Also, body composition will be assessed by dual x-ray absorptiometry (DXA) scan on the first day of the first phase and within the last 2 days of each treatment period. Blood samples will be collected on the first and last 2 days of each treatment phase whereas urine samples will be collected on the first day of the first phase plus the last day of each phase to be analyzed for specific biomarkers.

Discussion: This trial protocol is designed to evaluate the hypotensive potential of consuming whole HSP, and HSP+, in comparison to casein protein. This study will be the first trial investigating the potential anti-hypertensive benefit of dietary hemp protein plus bioactive peptide consumption in humans.

Trial registration: National Clinical Trial (NCT), ID: NCT03508895. Registered on 28 June 2018. Retrospectively registered on the publicly accessible Registry Databank at ClinicalTrials.gov (http://ClinicalTrials.gov).

Keywords: Bioactive peptides; Casein; Hemp seed protein; Hypertension.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Schematic flow diagram of the trial protocol
Fig. 2
Fig. 2
Representation of the trial enrollment, interventions and analysis

References

    1. Bancej CM, Campbell N, McKay DW, Nichol M, Walker RL, Kaczorowski J. Home blood pressure monitoring among Canadian adults with hypertension: results from the 2009 Survey on Living with Chronic Diseases in Canada. Can J Cardiol. 2010;26(5):e152–e1e7. doi: 10.1016/S0828-282X(10)70382-2.
    1. Lim SS, Vos T, Flaxman AD, Danaei G, Shibuya K, Adair-Rohani H, et al. A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380(9859):2224–2260. doi: 10.1016/S0140-6736(12)61766-8.
    1. Lawes CM, Vander Hoorn S, Rodgers A. International Society of Hypertension. Global burden of blood-pressure-related disease, 2001. Lancet. 2008;371(9623):1513–1518. doi: 10.1016/S0140-6736(08)60655-8.
    1. McAlister FA, Wilkins K, Joffres M, Leenen FH, Fodor G, Gee M, et al. Changes in the rates of awareness, treatment and control of hypertension in Canada over the past two decades. CMAJ. 2011;183(9):1007–1013. doi: 10.1503/cmaj.101767.
    1. Robitaille C, Dai S, Waters C, Loukine L, Bancej C, Quach S, et al. Diagnosed hypertension in Canada: incidence, prevalence and associated mortality. CMAJ. 2012;184(1):E49–E56. doi: 10.1503/cmaj.101863.
    1. Kalil GZ, Haynes WG. Sympathetic nervous system in obesity-related hypertension: mechanisms and clinical implications. Hypertens Res. 2012;35(1):4. doi: 10.1038/hr.2011.173.
    1. Te Riet L, van Esch JH, Roks AJ, van den Meiracker AH, Danser AH. Hypertension: renin-angiotensin-aldosterone system alterations. Circ Res. 2015;116(6):960–975. doi: 10.1161/CIRCRESAHA.116.303587.
    1. Hall JE, do Carmo JM, da Silva AA, Wang Z, Hall ME. Obesity-induced hypertension: interaction of neurohumoral and renal mechanisms. Circ Res. 2015;116(6):991–1006. doi: 10.1161/CIRCRESAHA.116.305697.
    1. Tunuguntla A. Emerging drug therapies for the management of acute decompensated heart failure. Tenn Med. 2007;100(11):33–37.
    1. Appel LJ, Brands MW, Daniels SR, Karanja N, Elmer PJ, Sacks FM, et al. Dietary approaches to prevent and treat hypertension: a scientific statement from the American Heart Association. Hypertension. 2006;47(2):296–308. doi: 10.1161/01.HYP.0000202568.01167.B6.
    1. Altorf-van der Kuil W, Engberink MF, Brink EJ, van Baak MA, Bakker SJ, Navis G, et al. Dietary protein and blood pressure: a systematic review. PloS one. 2010;5(8):e12102. doi: 10.1371/journal.pone.0012102.
    1. Teunissen-Beekman KF, van Baak MA. The role of dietary protein in blood pressure regulation. Curr Opin Lipidol. 2013;24(1):65–70. doi: 10.1097/MOL.0b013e32835b4645.
    1. Teunissen-Beekman KF, Dopheide J, Geleijnse JM, Bakker SJ, Brink EJ, de Leeuw PW, et al. Protein supplementation lowers blood pressure in overweight adults: effect of dietary proteins on blood pressure (PROPRES), a randomized trial. Am J Clin Nutr. 2012;95(4):966–971. doi: 10.3945/ajcn.111.029116.
    1. Appel LJ, Sacks FM, Carey VJ, Obarzanek E, Swain JF, Miller IER. et al. Effects of protein, monounsaturated fat, and carbohydrate intake on blood pressure and serum lipids: results of the OmniHeart randomized trial. J Am Med Assoc. 2005;294(19):2455–64. doi: 10.1001/jama.294.19.2455.
    1. He J, Wofford MR, Reynolds K, Chen J, Chen CS, Myers L, et al. Effect of dietary protein supplementation on blood pressure: a randomized, controlled trial. Circulation. 2011;124(5):589–595. doi: 10.1161/CIRCULATIONAHA.110.009159.
    1. He J, Gu D, Wu X, Chen J, Duan X, Chen J, et al. Effect of soybean protein on blood pressure: a randomized, controlled trial. Ann Intern Med. 2005;143(1):1–9. doi: 10.7326/0003-4819-143-1-200507050-00004.
    1. Cadee JA, Chang CY, Chen CW, Huang CN, Chen SL, Wang CK. Bovine casein hydrolysate (c12 Peptide) reduces blood pressure in prehypertensive subjects. Am J Hypertens. 2007;20(1):1–5. doi: 10.1016/j.amjhyper.2006.06.005.
    1. Li H, Prairie N, Udenigwe CC, Adebiyi AP, Tappia PS, Aukema HM, et al. Blood pressure lowering effect of a pea protein hydrolysate in hypertensive rats and humans. J Agric Food Chem. 2011;59(18):9854–9860. doi: 10.1021/jf201911p.
    1. Bouglé D, Bouhallab S. Dietary bioactive peptides: human studies. Crit Rev Food Sci Nutr. 2017;57(2):335–343. doi: 10.1080/10408398.2013.873766.
    1. Stamler J, Liu K, Ruth KJ, Pryer J, Greenland P. Eight-year blood pressure change in middle-aged men: relationship to multiple nutrients. Hypertension. 2002;39(5):1000–1006. doi: 10.1161/01.HYP.0000016178.80811.D9.
    1. Wheeler ML, Fineberg SE, Fineberg NS, Gibson RG, Hackward LL. Animal versus plant protein meals in individuals with type 2 diabetes and microalbuminuria: effects on renal, glycemic, and lipid parameters. Diabetes Care. 2002;25(8):1277–1282. doi: 10.2337/diacare.25.8.1277.
    1. Rebholz CM, Friedman EE, Powers LJ, Arroyave WD, He J, Kelly TN. Dietary protein intake and blood pressure: a meta-analysis of randomized controlled trials. Am J Epidemiol. 2012;176 Suppl_7:S27–S43. doi: 10.1093/aje/kws245.
    1. Brussaard JH, van Raaij JM, Stasse-Wolthuis M, Katan MB, Hautvast JG. Blood pressure and diet in normotensive volunteers: absence of an effect of dietary fiber, protein, or fat. Am J Clin Nutr. 1981;34(10):2023–2029. doi: 10.1093/ajcn/34.10.2023.
    1. Lu R-R, Qian P, Sun Z, Zhou X-H, Chen T-P, He J-F, et al. Hempseed protein derived antioxidative peptides: purification, identification and protection from hydrogen peroxide-induced apoptosis in PC12 cells. Food Chem. 2010;123(4):1210–1218. doi: 10.1016/j.foodchem.2010.05.089.
    1. Girgih AT, Alashi A, He R, Malomo S, Aluko RE. Preventive and treatment effects of a hemp seed (Cannabis sativa L.) meal protein hydrolysate against high blood pressure in spontaneously hypertensive rats. Eur J Nutr. 2014;53(5):1237–1246. doi: 10.1007/s00394-013-0625-4.
    1. Vasdev S, Stuckless J. Antihypertensive effects of dietary protein and its mechanism. Int J Angiol. 2010;19(1):e7–e20. doi: 10.1055/s-0031-1278362.
    1. DePeters EJ, Ferguson JD. Nonprotein nitrogen and protein distribution in the milk of cows. J Dairy Sci. 1992;75(11):3192–3209. doi: 10.3168/jds.S0022-0302(92)78085-0.
    1. Pal S, Ellis V. The chronic effects of whey proteins on blood pressure, vascular function, and inflammatory markers in overweight individuals. Obesity (Silver Spring) 2010;18(7):1354–1359. doi: 10.1038/oby.2009.397.
    1. Dong JY, Tong X, Wu ZW, Xun PC, He K, Qin LQ. Effect of soya protein on blood pressure: a meta-analysis of randomised controlled trials. Br J Nutr. 2011;106(3):317–326. doi: 10.1017/S0007114511000262.
    1. House JD. Neufeld J, Leson G. Evaluating the quality of protein from hemp seed (Cannabis sativa L.) products through the use of the protein digestibility-corrected amino acid score method. J Agric Food Chem. 2010;58(22):11801–11807. doi: 10.1021/jf102636b.
    1. Callaway J, Schwab U, Harvima I, Halonen P, Mykkanen O, Hyvonen P, et al. Efficacy of dietary hempseed oil in patients with atopic dermatitis. J Dermatol Treat. 2005;16(2):87–94. doi: 10.1080/09546630510035832.
    1. Callaway JC. Hempseed as a nutritional resource: an overview. Euphytica. 2004;140(1–2):65–72. doi: 10.1007/s10681-004-4811-6.
    1. Kaul N, Kreml R, Austria JA, Richard MN, Edel AL, Dibrov E. et al. A comparison of fish oil, flaxseed oil and hempseed oil supplementation on selected parameters of cardiovascular health in healthy volunteers. J Am Coll Nutr. 2008;27(1):51–8. doi: 10.1080/07315724.2008.10719674.
    1. Schwab US, Callaway JC, Erkkila AT, Gynther J, Uusitupa MIJ, Jarvinen T. Effects of hempseed and flaxseed oils on the profile of serum lipids, serum total and lipoprotein lipid concentrations and haemostatic factors. Eur J Nutr. 2006;45(8):470–477. doi: 10.1007/s00394-006-0621-z.
    1. Tapiero H, Mathe G, Couvreur P, Tew KD. I Arginine. Biomed Pharmacother. 2002;56(9):439–445. doi: 10.1016/S0753-3322(02)00284-6.
    1. Dong JY, Qin LQ, Zhang Z, Zhao Y, Wang J, Arigoni F, et al. Effect of oral L-arginine supplementation on blood pressure: a meta-analysis of randomized, double-blind, placebo-controlled trials. Am Heart J. 2011;162(6):959–965. doi: 10.1016/j.ahj.2011.09.012.
    1. Lorin J, Zeller M, Guilland JC, Cottin Y, Vergely C, Rochette L. Arginine and nitric oxide synthase: regulatory mechanisms and cardiovascular aspects. Mol Nutr Food Res. 2014;58(1):101–116. doi: 10.1002/mnfr.201300033.
    1. Rabelo LA, Ferreira FO, Nunes-Souza V, da Fonseca LJS, Goulart MOF. Arginase as a critical prooxidant mediator in the binomial endothelial dysfunction-atherosclerosis. Oxidative Med Cell Longevity. 2015. 10.1155/2015/924860.
    1. Pernow J, Jung C. Arginase as a potential target in the treatment of cardiovascular disease: reversal of arginine steal? Cardiovasc Res. 2013;98(3):334–343. doi: 10.1093/cvr/cvt036..
    1. Bagnost T, Ma L, da Silva RF, Rezakhaniha R, Houdayer C, Stergiopulos N, et al. Cardiovascular effects of arginase inhibition in spontaneously hypertensive rats with fully developed hypertension. Cardiovasc Res. 2010;87(3):569–577. doi: 10.1093/cvr/cvq081..
    1. Wu G, Bazer FW, Davis TA, Kim SW, Li P, Marc Rhoads J, et al. Arginine metabolism and nutrition in growth, health and disease. Amino Acids. 2009;37(1):153–168. doi: 10.1007/s00726-008-0210-y.
    1. Visek WJ. Arginine needs, physiological state and usual diets. A reevaluation. J Nutr. 1986;116(1):36–46. doi: 10.1093/jn/116.1.36.
    1. Udenigwe CC, Aluko RE. Food protein-derived bioactive peptides: production, processing, and potential health benefits. J Food Sci. 2012;77(1):R11–R24. doi: 10.1111/j.1750-3841.2011.02455.x.
    1. Aluko RE. Antihypertensive peptides from food proteins. Annu Rev Food Sci Technol. 2015;6:235–262. doi: 10.1146/annurev-food-022814-015520.
    1. Girgih AT, He R, Aluko RE. Kinetics and molecular docking studies of the inhibitions of angiotensin converting enzyme and renin activities by hemp seed (Cannabis sativa L.) peptides. J Agric Food Chem. 2014;62(18):4135–4144. doi: 10.1021/jf5002606.
    1. Ishida Y, Shibata Y, Fukuhara I, Yano Y, Takehara I, Kaneko K. Effect of an excess intake of casein hydrolysate containing Val-Pro-Pro and Ile-Pro-Pro in subjects with normal blood pressure, high-normal blood pressure, or mild hypertension. Biosci Biotechnol Biochem. 2011;75(3):427–433. doi: 10.1271/bbb.100560.
    1. Thayer AM. Improving peptides. Chem Eng News Arch. 2011;89(22):13–20. doi: 10.1021/cen-v089n022.p013.
    1. Cicero AF, Gerocarni B, Laghi L, Borghi C. Blood pressure lowering effect of lactotripeptides assumed as functional foods: a meta-analysis of current available clinical trials. J Hum Hypertens. 2011;25(7):425–436. doi: 10.1038/jhh.2010.85.
    1. Foltz M, Meynen EE, Bianco V, van Platerink C, Koning TM, Kloek J. Angiotensin converting enzyme inhibitory peptides from a lactotripeptide-enriched milk beverage are absorbed intact into the circulation. J Nutr. 2007;137(4):953–958. doi: 10.1093/jn/137.4.953.
    1. Celik G, Yilmaz S, Ergulu Esmen S. Non-dipping blood pressure patterns and arterial stiffness parameters in patients with Behcet’s disease. Hypertens Res. 2015;38(12):856–61.
    1. Koutroumbas G, Georgianos PI, Sarafidis PA, Protogerou A, Karpetas A, Vakianis P, et al. Ambulatory aortic blood pressure, wave reflections and pulse wave velocity are elevated during the third in comparison to the second interdialytic day of the long interval in chronic haemodialysis patients. Nephrol Dial Transplant. 2015;30(12):2046–53.
    1. Baykan AO, Gur M, Acele A, Seker T, Quisi A, Yildirim A, et al. Coronary collateral development and arterial stiffness in patients with chronic coronary total occlusions. Scand Cardiovasc J. 2015;49(4):228–234. doi: 10.3109/14017431.2015.1062130.
    1. Sarafidis PA, Georgianos PI, Karpetas A, Bikos A, Korelidou L, Tersi M, et al. Evaluation of a novel brachial cuff-based oscillometric method for estimating central systolic pressure in hemodialysis patients. Am J Nephrol. 2014;40(3):242–250. doi: 10.1159/000367791.
    1. Coyne T, Ibiebele TI, Baade PD, Dobson A, McClintock C, Dunn S, et al. Diabetes mellitus and serum carotenoids: findings of a population-based study in Queensland, Australia. Am J Clin Nutr. 2005;82(3):685–693. doi: 10.1093/ajcn/82.3.685.
    1. Haffner SM, Miettinen H, Stern MP. The homeostasis model in the San Antonio Heart Study. Diabetes Care. 1997;20(7):1087–1092. doi: 10.2337/diacare.20.7.1087.
    1. Gallinelli A, Nicoli A, Capodanno F, Valli B, Facchinetti F, La Sala GB. Nitric oxide as an early marker of human embryo metabolic cleavage in ART using fresh or thawed oocytes. Eur J Obstetrics Gynecol Reprod Biol. 2009;142(1):48–52. doi: 10.1016/j.ejogrb.2008.09.005.

Source: PubMed

スポンサーと協力者

医学的状態

薬物療法

3
購読する