Suppression of Nitric Oxide Production and Cardiovascular Risk Factors in Healthy Seniors and Hypercholesterolemic Subjects by a Combination of Polyphenols and Vitamins

Abstract

Background Dysregulated immune function associated with ageing has been implicated in a variety of human diseases. We have demonstrated the anti-inflammatory properties of resveratrol, pterostilbene, morin hydrate, quercetin, δ-tocotrienol, riboflavinin a variety of experimental animal models, and determined that these compounds act by inhibiting proteasome activity. Aims To determine whether serum nitric oxide (NO) levels increase with age in humans, and whether the combined cholesterol-lowering and inflammation-reducing properties of resveratrol, pterostilbene, Morin hydrate, quercetin, δ-tocotrienol, riboflavin, and nicotinic acid would reduce cardiovascular risk factors in humans when used as nutritional supplements with, or without, other dietary changes. Methods Elderly human subjects were stratified into two groups based on total serum cholesterol levels. Initial total serum cholesterol levels were normal and elevated in Group 1 and 2 subjects, respectively. Baseline serum NO, C-reactive protein (CRP), γ-glutamyltransferase (γ-GT) activity, uric acid, total antioxidant status (TAS), total cholesterol, HDL-cholesterol, LDL-cholesterol, and triglycerides levels were established over a four week period. Group 1 subjects subsequently received nutritional supplementation with one of two different combinations (NS-7 = 25 mg of each, resveratrol, pterostilbene, quercetin, δ-tocotrienol, nicotinic acid, morin hydrate or NS-6 = morin hydrate replaced with quercetin, 50 mg/capsule). Group 2 subjects also received these nutritional supplements (two capsules/d), but an AHA Step-1 diet was also implemented. After these interventions were administered for four weeks, the above parameters were re-measured and changes from baseline levels determined. Nitric acid (NO) levels in children, young adults, and seniors were also compared. Results The key results of the current study were: 1) that serum NO levels were significantly increased in seniors compared to both children (~80%) and young adults (~65%); 2) that the intake of two capsules/d of NS-7 or NS-6 for four weeks significantly (P < 0.05) decreased serum NO (39%, 24%), CRP (19%, 21%), uric acid (6%, 12%) levels, and γ-GT activity (8%, 6%), respectively in free-living healthy seniors; 3) that serum NO (36%, 29%), CRP (29%, 20%), uric acid (6%, 9%) γ-GT activity (9%, 18%), total cholesterol (8%, 11%), LDL-cholesterol (10%, 13%), and triglycerides (16%, 23%) levels were significantly (P < 0.02) decreased in hypercholesterolemic subjects restricted to AHA Step-1 diet plus intake of SN-7 or SN-6 (two capsules/d), respectively; 4) that TAS was increased (3%, 9%; P < 0.05) in free-living healthy seniors receiving NS-7 or NS-6 alone, and in hypercholesterolemic subjects plus AHA Step-1 diet (20%, 12%; P < 0.02) with either of the combinations tested. Conclusions Serum NO levels are elevated in elderly humans compared to children or young adults. Diet supplementation with combinations of resveratrol, pterostilbene, morin hydrate, quercetin, δ-tocotrienol, riboflavin,...

Nutritional Supplement-5 with a Combination of Proteasome Inhibitors (Resveratrol, Quercetin, δ-Tocotrienol) Modulate Age-Associated Biomarkers and Cardiovascular Lipid Parameters in Human Subjects

“…The main differences between our recently published study and the present one are as follows: The only complaint during our most recent clinical trial was recorded by female participants, whose urine color became deep yellow due to riboflavin in the NS-6 or NS-7 mixtures [12]. Several participants failed to complete the trial due to concerns about their urine color.…”

“…Over the last several years, our research has focused on the role of the proteasome in inflammatory responses [11]. We have identified a number of compounds that have the capacity to inhibit cellular proteasomes, and demonstrated that these compounds have anti-inflammatory properties, largely through their capacity to inhibit NF-κB activation [12-16]. Age-associated altered redox imbalances can activate the immune system through increased production of superoxide (O 2 - ), hydroxyl radical (*OH), hydrogen peroxide (H 2 O 2 ), reactive nitric oxide (NO), peroxynitrite (ONOO - ), and reactive lipid aldehydes [2].…”

“…We recently reported that NO levels increase with age, that NO levels are significantly higher in hypercholesterolemic, as compared to humans with normal cholesterol levels, and that plasma NO levels are decreased by dietary supplementation with acombination of resveratrol, pterostilbene, quercetin, δ-tocotrienol, riboflavin, morin hydrate, and nicotinic acid (NS-7, or NS-6) [12]. Levels of other markers of cardiovascular risk (CRP, γ-glutamyl-transferase {γ-GT} activity and uric acid) were also reduced via these dietary supplementations [12]. Dietary supplementation with NS-7 or NS-6 did not have an effect on total cholesterol, LDL-cholesterol, or triglyceride levels of adults (~65 years old) with normal cholesterol levels.…”

“…Dietary supplementation with NS-7 or NS-6 did not have an effect on total cholesterol, LDL-cholesterol, or triglyceride levels of adults (~65 years old) with normal cholesterol levels. With hypercholesterolemic subjects, however, combined intervention with dietary supplementations and restriction to the AHA Step-1 diet reduced modestly serum total, LDL-cholesterol, and triglycerides levels [12]. …”

Fermented Papaya Preparation Restores Age-Related Reductions in Peripheral Blood Mononuclear Cell Cytolytic Activity in Tube-Fed Patients

“…Immunity is regulated by the thymus gland, and thymus gland function is known to gradually decrease with age [6–11]; therefore, the immune system is generally weaker in older patients than in younger patients. Large mononuclear lymphocytes, known as natural killer (NK) cells because of their spontaneous killing of cancer cells and antiviral properties [12–14], are a component of adaptive immunity; it is well known that they exhibit reduced function and altered composition with aging [12,15].…”