Hypertension (HTN) is a major risk factor for cardiovascular disease (CVD) and cognitive decline. Elevations in blood pressure (BP) leading to HTN can be found in young adults with increased prevalence as people age. Oats can decrease CVD risk via an established effect of β-glucan on the attenuation of blood cholesterol. Oats deliver several beneficial dietary components with putative beneficial effects on BP or endothelial function, such as β-glucan, γ-amino butyric acid (GABA), and phytochemicals such as avenanthramides.
1. Introduction
Blood pressure (BP) is an essential aspect of overall health and, when elevated, can lead to arterial damage and stroke
[1][2][3]. Moreover, robust and consistent evidence indicates that elevated systolic blood pressure (SBP) and diastolic blood pressure (DBP) are associated with increased risk for cardiovascular disease (CVD) and end-stage renal disease
[2][4]. High BP, which includes prehypertension and Stage 1 and Stage 2 hypertension (HTN), is a leading cause of death and morbidity worldwide and is also implicated in cognitive decline, which can occur as early as young adulthood with increased prevalence in older people
[2][5][6]. The prevalence of HTN in older adults is substantial, and the 40-year risk of developing HTN after age 45 is estimated to be 93%, 92%, 86%, and 84% for African-Americans, Hispanics, white, and Chinese Americans, respectively
[2]. A major concern with high BP is the prevalence of undiagnosed HTN due to the lack of noticeable symptoms, which is why it is called the silent killer
[7].
Reducing SBP and DBP by 2 mmHg or 1 mmHg, respectively, is associated with a 10% reduction in the population risk of CVD, and a reduction of 5 mmHg is associated with reductions in stroke (34%) and coronary heart disease (21%)
[8]. High BP is related to body weight, and every 1 kg of weight loss in people who are overweight or obese can decrease BP by around 1 mmHg
[2][4]. Diet is an important factor as a primary intervention for prehypertension and an adjunct therapy when pharmacological interventions are warranted
[2][7]. These include whole dietary modifications, such as the DASH diet, that are characterized by lower sodium and red meats and higher vegetables and low-fat dairy products
[9] or supplementation with nutraceuticals such as potassium, magnesium, L-arginine, vitamin C, cocoa flavonoids, beetroot juice, coenzyme Q10, controlled-release melatonin, and aged garlic extract
[10]. In particular, dietary fiber has received a great deal of attention for BP management since diets high in fiber are often promoted for weight loss/weight-loss maintenance and are associated with decreased risk of CVD and many other diseases
[7][11]. Indeed, oat consumption can increase satiety and reduce energy intake, and can subsequently help promote the maintenance of a healthy weight by providing health-promoting dietary fibers
[12][13][14].
Among the different types of dietary fiber, a relationship between the soluble fiber β-glucan and decreases in total- and LDL-cholesterol, risk factors for CVD, is well established
[15][16][17]. For example, an FDA Health Claim for β-glucan, stating that 3 g of soluble fiber per day from oat foods in a diet low in saturated fat and cholesterol may reduce the risk of heart disease, has been allowed
[18]. Notably, oats contain more soluble fiber than other grains, primarily in the form of β-glucan. A recent study showed that an oat beverage providing 3 g β-glucan daily could lower age-dependent systemic chronic inflammation and CVD risk to promote healthy aging in subjects with borderline high cholesterol
[19][20]. Therefore, oats can have a beneficial effect on the inflammatory system and the aging trajectory in a subset of subjects presenting elevated risk factors. Many early studies on oat fiber and CVD also have reported reductions in BP, which was often attributed to β-glucan
[11]. However, oats contain many other components that have been shown to beneficially impact metabolism, including phenolics (e.g., avenanthramides, flavonoids, tocols), a novel protein (avenalin), the anti-stress γ-aminobutyric acid (GABA), and minerals (potassium, magnesium)
[7][17][21][22][23]. Therefore, the health benefits, although often attributed to β-glucan alone, may involve other components in oat products.
2. Effects of Oat on Blood Pressure
2.1. Oats and Blood Pressure
Subgroup analysis for β-glucan sources showed reductions in SBP and DBP [8][24]. In a meta-analysis of normotensive adults, sensitivity analysis suggested that neither age nor body mass index (BMI) had a marked impact on the effect of fiber interventions and BP [8]. A separate meta-analysis including adults with HTN found no effects from fiber amounts, study design, and type of administration; although higher reductions were seen in interventions lasting more than 7 weeks, the reductions in BP were also influenced by the HTN status in subjects [24]. Taken together, these data support that responses are more robust in HTN than in normotensive subjects and that the amount of fiber/intervention product is essential. However, although the oat findings were attributed to β-glucan, the interventions utilized in the meta-analyses included studies primarily using oatmeal/porridge, oat cereal, and foods made with oat bran, not isolated β-glucan fiber. Therefore, although some conclusions were attributed to β-glucan effects, the other components in oats may also be contributing to the effect of lowering BP.
2.2. Oat Composition and Bioactives
Oat is unlike many other cereal grains based on its composition; it is primarily consumed as a whole grain, although oat bran is often used in many food applications [7]. Several oat varieties are grown across the globe and include husked oats (Avena sativa L.), large naked oats (Avena nuda I.), small naked oats (Avena nudibrevis), wild red oats (Avena steriles), and wild oats (Avena fatua) among others [7][21].
Oats are high in protein compared to other grains, which is found primarily in the bran with some in the germ
[7]. The protein quality is also greater compared to that of many other plant sources, with higher lysine and lower proline and glutamine than other common grains, making it nearly the same quality as that of eggs, soy, milk, and meat proteins
[7][21][23]. Oat groat is also composed of around 5–12% fats, primarily palmitic (16:0) and the unsaturated fatty acids, and oleic (18:1) and linoleic (18:2) acids
[23]. Much attention has focused on the carbohydrate content of oats, primarily fiber. Compared to other major grains in human food consumption, oat is among the highest in fiber, delivering ~10.3 g of dietary fiber per 100 g of oats
[7][21], of which 3–8 g is β-glucan
[23]. Oats are also a source of tocols (tocopherols and tocotrienols), supporting vitamin E nutriture
[21][25]. The amount of tocols in oats ranges from 0.5 to 3.61 mg/100g, with the most abundant tocopherol being α-tocopherol
[25]. Oats provide vitamin A, β-carotene, vitamin B1, and vitamin B6, and the minerals potassium (355 mg/100 g seeds) and phosphorus (342 mg/100 g seeds), as well as calcium, magnesium, iron, zinc, copper, and manganese
[21].
Oats also contain an array of phenolics, also called phytochemicals or phytonutrients, which have gained interest due to their potential impacts on human health. Notably, oat is the only food that contains avenanthramides, a group of phenolic alkaloids
[22][23][26]. Soycan et al.
[27] assessed the polyphenolics and avenanthramides in a range of commercial oat products available to consumers, including oat bran concentrate, flaked oats, and rolled oats
[27]. Oat bran concentrate had the highest amounts of phenolic acids and avenanthramides, although all oat foods had relatively high amounts of these bioactives, delivering 15.79–25.05 mg total phenolic acids and 1.1–2.0 mg avenanthramides in a 40 g portion of oat product
[27].
Oat Sprouts as a Source of Bioactives
Oat sprouts have been shown to maintain the high-quality protein characteristics and similar fiber content of whole oats
[28]. Proteins are one of the major fractions of grains and these are strongly affected by germination, whereby storage proteins are broken down to provide small peptides and amino acids to the growing embryo. Oat germination was shown to increase total protein and both essential and non-essential amino acid contents, although these are dependent on germination conditions (e.g., temperature and duration)
[29][30]. Germination also increased protein digestibility
[31]. This is important in light of the low protein digestibility of plant proteins in general
[32]. Although fiber content is also consistent between oat grain and sprouted oat, germination leads to significant hydrolysis of β-glucan, possibly due to the increased activity of endogenous β-glucanases, resulting in a decrease of around 40%
[30].
Sprouted oats contain much higher levels of important minerals, including calcium, iron, zinc, and magnesium, and interestingly, up to 30-fold higher levels of GABA
[28][33][34]. Sprouted oats show an increase in free phenolics such as avenanthramides, with between 3- and 5-fold higher phenolic content, which could be due to de novo synthesis or release of the compounds from the cell wall and fiber components
[28][35][36]. Due to the beneficial nutritional profile and positive sensory characteristics of sprouted oats, germination of oat products is being explored as a base for innovative functional foods, including gluten-free fermented functional beverages
[28].
Antihypertensive Effects of Oats
BP control involves a complex interplay among renal function, vascular health, and neural regulatory pathways, arising from genetic factors and diet and lifestyle effects. Some data suggest that early-life factors, such as maternal nutrition and early-life oxidative stress, can lead to HTN in adulthood
[37]. Pathophysiological conditions or poor lifestyle choices can elicit oxidative stress and increase levels of reactive oxygen species (ROS) that are a major contributor to vascular dysfunction and remodeling, leading to HTN (
Figure 1). In particular, ROS decrease nitric oxide (NO) synthesis, and HTN is associated with a reduction in antioxidant capacity and bioavailability. Treatments to manage high BP are equally complex and often involve multiple, personalized modalities. Diet and lifestyle are cornerstones of public health recommendations for prevention and components of therapeutic programs to manage HTN. For example, initial guidelines recommend diet and lifestyle alterations as the first step in mitigating elevated BP and Stage 1 HTN, followed by the inclusion of pharmacological and more targeted approaches for non-responsive cases and above Stage 1 HTN
[2]. Traditional lifestyle changes include weight management, smoking cessation, low-sodium diets, and decreasing alcohol and caffeine consumption
[6]. Plant-based diets are also associated with lower risk of HTN
[38]. However, it is becoming increasingly clear that functional ingredients in foods, such as dietary fibers, phenolic acids, functional peptides, and amino acids, can impact BP through numerous mechanisms (
Figure 1).
Figure 1. Mechanism of action of the anti-hypertensive effects of oat bioactives. (A) Gut microbiome-mediated metabolism of oat dietary fibers can increase circulating short-chain fatty acids (SCFA) involved in the reduction of hypertension, in part via reduction of p-cresyl sulfate, associated with vascular function (vasodilation) and cellular oxidative damage. In the endothelial cells (EC), avenanthramides (AVA) and phenolic acids (PA) induce vasodilation and enhance vascular function by endothelial nitric oxide (NO) synthase (eNOS) and by inhibiting NADPH oxidases’ regulation of NO degradation. Furthermore, angiotensin II-mediated vasoconstriction, endothelial dysfunction, and hypertension can be directly inhibited by oat saponins or indirectly by AVA inhibition of renin and GABA inhibition of angiotensin-converting enzyme (ACE) upstream of angiotensin II. GABA, AVA, and oat saponin can help improve endothelial cell function. (B) Risk factors can elicit a pathological rise of systemic inflammation and elevated intracellular levels of reactive oxygen species (ROS) that are critically implicated in the etiology of hypertension. Oats’ PA and AVA are anti-inflammatory and antioxidant bioactives that could contribute to the maintenance of a healthy BP.
Dietary Fiber and SCFA
Diets high in fiber, particularly soluble fibers (e.g., β-glucan), are recommended to decrease elevated BP [8][11][24][39][40][41][42], and some evidence suggests they function by decreasing glucose uptake and therefore decreasing insulin release [43]. Emerging evidence suggests a healthy microbiome is also important in BP management [7][15][44][45]. For example, SCFAs produced by the microbiota have been shown to have vasodilating effects and anti-inflammatory properties, which can attenuate hypertensive tissue damage [7]. In a clinical pilot study, increases in fecal SCFA decreases serum p-cresyl sulfate, and improvements in endothelial function via flow-mediated dilation (FMD) have been observed after consumption of a pasta enriched with barley β-glucans [46][47]. However, in another study with 210 mildly hypercholesterolemic Chinese adults, 80 g oats delivering 3 g β-glucans and 56.8 g polyphenols did not significantly change plasma SCFA but did result in putative beneficial changes in gut microbiota after 45 days [48].
Oat Phenolics and Avenanthramides
Avenanthramides have established physiological properties, including anti-inflammatory, antioxidant, and anti-thrombotic benefits, with reportedly higher antioxidant activity compared to that of other phenolic compounds in vitro [22][23]. Cell culture studies have found that avenanthramides can increase NO levels and endothelial NO synthase expression in vascular smooth muscle cells and endothelial cells, thus potentially affecting NO-dependent vasodilation [17][36]. In vitro data suggest the effect on NO may occur via reducing cellular superoxide levels, or acting as NADPH oxidase inhibitors, thereby reducing NO degradation [49]. Avenanthramides have also been shown to inhibit the adhesion of monocytes to vascular endothelial cells and release inflammatory activators from macrophages, and exert anti-proliferative and pro-apoptotic activities in transformed cells [26][50]. Increasingly, inflammation is being linked to HTN and, particularly hypertensive tissue damage [51]. Further, monocytes, macrophages, and dendritic cells of the immune system can promote elevations in BP [51]. Therefore, the potential beneficial impact of oat polyphenols on inflammation and immune function could also contribute to the attenuation of elevated BP.
Oat Bioactive Peptides and γ-Aminobutyric Acids (GABA)
Oats are the only cereals to contain the globulin or legume-like protein avenalin, as well as gluten, zein, and avenin proteins
[21]. Aside from providing protein nutriture, emerging in vitro and in silico data indicate oats contain bioactive peptides. For example, in vitro and animal studies suggest oat protein-derived peptides have broad antioxidant activity and can inhibit cyclooxygenase-1, α-amylase, and DPP-IV activities, suggesting beneficial effects for supporting cardiometabolic health
[7][52][53][54][55][56][57]. Specific to BP, an oat globulin peptide (peptide SSYYPEK, 890.4 Da) prepared by hydrolysis has shown the ability to inhibit angiotensin-1-converting enzyme (ACE) activity and suppress renin and intracellular endothelin-1 in spontaneously hypertensive rats at 100 to 150 mg/kg body weight
[58]. Peptides of different oat protein isolates were investigated by in silico hydrolysis and chemical synthesis methods with several peptides and found to inhibit the ACE enzyme (by 86.5–96.5%) and renin (40.5–70.9%) in vitro at 1 mg/mL
[57]. Moreover, strong ACE-inhibitory activity has been found in oat bioactive peptides (<3 kDa) produced by simulated gastrointestinal digestion, with the half-maximal inhibitory concentration (IC50) for different hydrolysates of 35 and 85 μg/mL
[59]. The ACE is an important target for many BP interventions as it regulates the renin–angiotensin–aldosterone system, which is the primary metabolic pathway controlling arteriolar vasoconstriction and intravascular fluid volume and, thus, BP
[57].
Much interest has been generated around GABA, which is a non-protein amino acid with numerous beneficial activities, including reducing stress and enhancing sleep in human trials
[60]. GABA shows great promise as an intervention to help manage healthy BP and has a positive safety profile
[60][61]. Although GABA is an important neurotransmitter, studies have shown that dietary GABA does not appreciably transit the blood–brain barrier; therefore, the mechanism(s) supporting these clinical findings do not relate to the effect on brain chemistry
[61]. In vitro studies support the effect of GABA as an ACE inhibitor at IC50 values up to 0.70 ± 0.07 mg/mL, and studies in spontaneously hypertensive rats at 0.3–300 mg/kg (intraduodenal) GABA have shown dose-dependent decreases in BP
[61]. In humans, clinical studies on fermented foods, such as fermented milk and soy products, delivering between 0.25 mg/d and 18,000 mg/d have been published and shown significant decreases in BP (<10% change), with BP returning to baseline levels when the food intervention was discontinued
[60]. As noted above, increased levels of GABA are found in oats after fermentation or germination
[28][34][62][63][64]. Sprouted oat powder has been shown to contain ~55 mg GABA/100 g
[28], which is within the range seen as active in lowering BP in clinical studies
[60].