Natural Plant-derived Ingredients for Hypertension
The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure, defines hypertension as systolic blood pressure above 140mmHg and diastolic blood pressure above 90mmHg. Normal blood pressure is below 120mmHg/80 mmHg(1).
The disease is responsible for aboutto 13% of deaths in the world according to the World Health Organization (WHO). In 2008, almost one quarter of all deaths globally, about 13.4 million people, were due to heart disease, stroke, or other vascular diseases that may be related to high blood pressure(2).
Approximately 19% of adults aged 20-79 years in Canada(3) and 33% in the United States have high blood pressure with the risk increasingwith age(4). Over 53% of those between 60-79 years have elevated blood pressure. And 14% take antihypertensive medications yet their blood pressure are not under control. Even with today’s diagnostic procedures, about 16% of Americans with hypertension are unaware of their condition.
In the WHO report(5), “WHO/ISH Hypertension Guidelines” it was stressed that,“Hypertension is a growing cardiovascular risk factor globally due to the increase in lifespan and contributing conditions such as obesity. Treatments for hypertension are effective in preventing cardiovascular disease and improving quality of life, but hypertension still exists as a significant unmanaged condition.”
In treating hypertension, alternatives to pharmaceutical drugs (that may have toxic or significant side effects) are being investigated. Researchers are exploring a class of compounds called bioactive peptides which although they may have less therapeutic effect, would not have the same serious side effect as drugs. An intriguing focus is the beneficial blood pressure lowering properties of peptide fractions contained in flaxseed and peas. These plant products have also be shown to have significant antioxidant, anti-inflammatory, and immune system modulating effects. In addition, flaxseed is high in fiber, lignans and the omega 3 fatty acid, alpha-linolenic acid, while peas are rich in fiber, minerals, and protein(7, 8).
Both flaxseed and peas contain high-quality essential amino acid profilesand an abundance of branched chain amino acids(8, 9). Their bioactive properties lie within the hydrolysate fraction of the protein component.
A number of food-grade techniques including solubilization, precipitation, enzymatic digestion, and ultra-filtration have been developed to produce protein precipitates which are then converted into hydrolysates(8, 9). Hydrolysates are of interest as they are small enough to bypass digestion in the gastrointestinal tract, and therefore can be tested for hypotensive and other properties.
Specific hydrolysates derived from flaxseed have antioxidant properties in their ability to “quench” damaging free radicals and provide protection against lipid peroxidation(9).In particular, sulphur-containing, acidic, and hydrophobic amino acids show potent free radical scavenging properties against DPPH and hydroxyl radicals. Hydrolysates rich in the amino acids, lysine and leucine appear to be effective scavengers of superoxide radicals(9). In subsequent research, flaxseed hydrolysate was further purified to contain a high branched chain amino acid content which yielded potent protection of linoleic acid by scavenging free radicals including superoxide, hydroxyls, and 2,2-diphenyl-1-picrylhydrazyl. This hydrolysate blend may be an ideal candidate treatment for individuals with pro-inflammatory conditions(13).
With regard to hypertension, work has been conducted with peptides from both flaxseed and peas. Blood pressure is controlled through a series of enzyme reactions known as the renin-angiotensin cascade, the most important of which is the Angiotensin Converting Enzyme (ACE). This enzyme converts Angiotensin I to Angiotensin II which increases blood pressure. It does so by causing constriction of the arteries and stimulating the release of aldosterone in the adrenal cortex, that act to enhance salt retention and water by the kidneys. Angiotensin II can also degrade bradykinin, a vasodilator. The ultimate result of these actions is an increase in blood volume and hence pressure(11, 12). Flaxseed protein hydrolysates have been shown to inhibit ACE activity and therefore reduce the production of Angiotensin II(9).
Flaxseed hydrolysates may also positively influence the activity of nitric oxide (NO), an important molecule that regulates vascular tone, neurotransmission, and the immune system. Underproduction of NO can cause vasoconstriction and an increase in blood pressure. And an overproduction of NO can cause oxidative damage and an inflammatory response.
NO is produced by the enzyme nitric oxide synthase (NOS) which is dependent upon the protein, calmodulin. Flaxseed hydrolysate fractions have been reported to reduce by modifying the structure of calmodulin(14). Thus, these hydrolysates may help re-balance an overproduction of NO and reduce the onset of oxidative stress and inflammation.
The physiological benefits of hydrolysates from the protein component of field pea have also been investigated(8,17).
Pea protein hydrolysates (PPH) were found to reduce the production of several pro-inflammatory molecules including tumor necrosis factor – alpha (TNF-α) (-35%), and interleukin-6 (IL-6) (-80%). In a mouse model, ingestion of PPH resulted in an increase in the immune regulators immunoglobulin A+, IL-6, IL-4+, IL-10+, and interferon gamma (IFN-γ+) which are produced in the gut (15). In another study, PPH also protected linoleic acid from oxidation (8).
With regard to its hypotensive effects, PPH fractions, like flaxseed hydrolysates have been demonstrated to reduce the two key enzymes responsible for increasing blood pressure, ACE and renin, each by 50% (16).
Following the feeding of 100 mg or 200 mg/kg body weight of PPH, systolic blood pressure was reduced in an animal model of hypertension, the spontaneously hypertensive rat (SHR). The greatest reduction (19 mmHg) was seen with the 200 mg/kg body weight dose. In contrast, a pea protein isolate had no effect on blood pressure, indicating that bioactivity resides in the hydrolysate fraction (17).
The effects of PPH in an animal model of kidney disease have been documented (17). Rats were fed diets as follows: a casein control, 0.5% as PPH, or 1.0% as PPH. Reductions in blood pressure were as great as 29 and 25 mmHg for systolic and diastolic blood pressure, respectively, in the PPH treatment groups. The decreases were attributable to reductions in Angiotensin II levels and mRNA expression of renin.As noted, renin is responsible for converting the first substrate of the renin-angiotensin cascade; when renin is inhibited so is Angiotensin II.
In a pilot randomized double-blinded placebo controlled crossover study in 7 humans, participants drank either a placebo, 1.5 g/day of PPH, or 3.0 g/day of PPH in juice. By the second week, reductions in systolic blood pressure over placebo of 5 to 6 mmHg were observed for the 3.0 g/day PPH dose (17). Larger multi-centre human studies are being planned in order to strengthen the evidence regarding the hypotensive properties of food protein hydrolysates in humans.
The potential for treating hypertension with natural bioactives from flaxseed and field peas is impressive. It may only be a matter of time before control of the silent killer may be possible – through the melding of agricultural and health research innovation.
1. Chobanian AV, Bakris GL, Black HR, et al. 2003. Seventh joint committee on prevention, detection, evaluation, and treatment of high blood pressure. Hypertension. 42:1206-1252.
2. World Health Organization. 2011. Top ten causes of death. Retrieved September 5th 2011 from: http://www.who.int/mediacentre/factsheets/fs310/en/index.html
3. Statistics Canada. 2010. Blood pressure in Canadian adults. Health Reports. 21(1): 1-10. Catalogue no: 82-003-XPE.
4. National Center for Health Statistics. Health, United States, 2010: With special feature on death and dying. Hyattsville, MD, 2011. Retrieved September 5th 2011 from: http://www.cdc.gov/nchs/data/hus/hus10.pdf#066
5. The World Health Organization. 2011. Cardiovascular disease: WHO/ISH hypertension guidelines. Retrieved September 5th 2011 from: http://www.who.int/cardiovascular_diseases/guidelines/hypertension/en/
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13. Udenigwe CC, Aluko RE. 2010. Antioxidant and Angiotensin converting enzyme-inhibitory properties of a flaxseed protein-derived high Fischer ratio peptide mixer. J Agric Food Chem. 58:4762-4768.
14. Omoni AO, Aluko RE. 2006. Effect of cationic flaxseed protein hydrolysate fractions on the in vitro structure and activity of calmodulin-dependent endothelial nitric oxide synthase. Mol Nutr Food Res. 50:958-966.
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16. Li H, Aluko RE. 2010. Identification and inhibitory properties of multifunctional peptides from pea protein hydrolysate. J Agric Food Chem. 58:11471-11476.
17. Li H, Prairie N, Udenigwe CC, et al. 2011. Blood Pressure Lowering Effect of a Pea Protein Hydrolysate in Hypertensive Rats and Humans. J Agric Food Chem.Sep 2. [Epub ahead of print].