Nitric oxide (NO) and superoxide anion radicals (SOR) are key molecular controllers of longevity and health span. L-arginine, the substrate of NO synthase, helps maintain a healthy balance between SOR and NO, promoting healthy aging. Antioxidant supplementation, including L-arginine, vitamin C, and others, protects against oxidative stress and damage by increasing NO production and bioavailability. Asymmetric dimethylarginine (ADMA) can uncouple NO generation, but L-arginine can displace it if sufficient amounts are available. Antioxidants like ascorbic acid can neutralize SOR and increase NO bioavailability, ultimately determining NO bioactivity and protection against age-related degeneration.
The anticipated demographic shift to an exponentially growing elderly population with increased morbidity poses the greatest challenge to society in history. This challenge raises a key scientific research question: Can we enhance human health span with the ever-increasing life expectancy resulting from advances in healthcare to prevent premature mortality? Aging is now the dominant risk factor for many degenerative disorders, for which mechanisms and dietary or environmental modulators remain poorly studied. The progressive increase in healthcare costs for non-communicable conditions and the rise in morbidity and mortality with advanced age is promoted by the cumulative bioenergetic burden upon the target population by the Western diet rich in sugar, fat, and salt. An imbalance between NO and SOR has been demonstrated in metabolic diseases such as diabetes and obesity. Antioxidant protection can determine health. Nutrition is decisive in determining health and healthcare costs. Precision nutrition, specific food, and biomatrix supplementation have been proposed to improve health by supplying sufficient macro and micronutrients. Adaptation and aging can be the opposite outcomes of dynamic developmental plasticity. The discovery and development of effective supplements containing amino acids and antioxidants that can restore and improve health even at an advanced age is a rapidly developing field of applied biosciences. Aging can be seen as a process of internal desynchronization induced by stress and aberrant-signaling-induced senescence and the concurrent loss of bioenergetic potential with a depletion of resources to prevent degenerative changes. Supplementation can maintain or even improve human health.
1. Adaptation and Aging
Lifetime exposure to high glucose and free fatty acid levels induces cumulative toxicity that limits adaptational and developmental plasticity. Premature aging and disease can result from nutrition rich in calories but poor in nutrients and natural agents. Supplementation rich in certain amino acids switches the metabolism to enhanced activity, efficacy, and oxidative phosphorylation capacity that improves mitochondrial redox regulation, inducing antioxidant adaptation by retrograde trophic pro-survival signaling. Since caloric restriction is often associated with malnutrition in humans, only bioenergetic agents such as the mitogenic and mitotrophic amino acids glutamine, proline, and arginine, which are abundantly present in proteins and peptides from pulses, grains, or collagen, can significantly improve the metabolism of mitochondria and stimulate their signaling. These amino acids are a real option to extend the human health span substantially. L-arginine and L-arginine-rich proteins or peptides can supply the necessary nutrients to reduce glycemic load, insulin resistance, and lipotoxicity by facilitating and enhancing fat oxidation and reducing glucose accumulation. Bioenergetic agents such as L-arginine and related amino acids have positive health effects, as demonstrated in the target population. These supplements induce bioenergetic stimulation, antioxidant protection, and ubiquitous regeneration that improve, restore, and maintain gut, skin, and joint health. The synergistic effects of this unique L-arginine-rich blend with antioxidant agents of high bioenergetic potency are discussed in the context of easy-to-handle approaches in supplementation aimed at improving, regaining, or maintaining health by improving the diet of the target population.
2. Nutrition and Health
Food and supplementation can be a decisive factor in maintaining health during aging and stress or enhanced demand for protective nutrients. Recent research indicates that a high intake of soy, pea, and pumpkin, rich in arginine, proline, and glutamine, can limit carbohydrate and fat toxicity associated with the Western diet and its predominant arginine-poor animal protein content. The use of amino acids like L-arginine together with the synergistically acting B vitamins, folate, vitamin B6, and vitamin B12, in preparations of premium quality and natural origin, opens up new perspectives in establishing a molecular, metabolic medicine that enables prevention, therapy, and rehabilitation for improving, maintaining, and restoring the health of older adults. Antioxidant protection and health-span extension seem to be possible through such an innovative approach as using amino acids and vitamins to enhance trophic retrograde NO signaling and thus life- and health-span. This review reveals how a holistic strategy employing amino acids like arginine combined with other nutrients can reverse chronic degenerative changes and trigger adaptive reactions and repair processes that restore regeneration via redox regulation and antioxidant protection. Novel, innovative approaches using highly sophisticated supplementation protocols have revealed the molecular mechanisms and physiological mediators of viability and survival that enable the organism to cope with internal and external stressors. All molecular mediators that induce such adaptive plasticity act as mitochondrial metabolism modifiers to increase trophic support through the enhanced supply and more efficient use of bioenergetic resources. The aim and goal of these approaches are to promote human fitness and health. The universal bioenergetic decline as a hallmark of stress and senescence can be corrected through supplementation-dependent mitochondrial support that restores metabolic control mechanisms essential to regeneration and repair.
3. Say NO to Aging
Aging is often associated with increased adiposity and altered reduced muscle mass or sarcopenia, including increased ectopic fat stores such as visceral, hepatic, and intermuscular fat, The age-dependent increase in asymmetric dimethylarginine (ADMA) levels and the upregulation of L-arginine depletion through enhanced arginase activity are the primary factors contributing to the alteration of the L-arginine/nitric oxide (NO) pathway associated with insulin resistance and endothelial dysfunction. These findings help explain the profound effects of precision supplementation, which involves an enhanced supply of L-arginine and other bioenergetic agents, in restoring metabolic control and reducing insulin resistance and lipotoxicity associated with enhanced superoxide anion radical and peroxynitrite formation in older adults. Currently, numerous clinical studies are being conducted to ensure that L-arginine supplementation and L-arginine-rich food can restore redox regulation in the elderly target population. Aging leads to decreased arginine: ADMA ratio and the nitric oxide: superoxide ratio, resulting in oxidative stress, inflammation, and degenerative changes that harm development and health. Supplementation with amino acids such as L-arginine and L-arginine-rich food through certain peptides and proteins can restore a healthy arginine: ADMA ratio.
Recent research confirms the crucial roles of metabolic pathways in regulating and determining human health. The ultimate goal is to explore new avenues that enable active living and healthy aging by preserving fitness throughout life. Upregulating nitric oxide bioavailability can prevent premature aging and neurodegeneration. Boosting the nitrate-nitrite-nitric oxide pathway improves gastrointestinal, cardiovascular, metabolic, and cognitive performance. Vegetables rich in nitrate, like spinach and beetroot, are a good source of nitric oxide, with beneficial effects on cardiovascular health and a lower risk of cardiovascular disease.
L-arginine has potent health-protecting effects, and its beneficial cardiovascular effects are well-established. The age-dependent decline of tryptophan in the brain is associated with toxic kynurenine formation, which impairs nitric oxide formation and leads to insulin resistance and metabolic syndrome.
Supplementation with L-arginine and B vitamins can stop the vicious cycle of oxidative stress and damage. Selectively increasing tryptophan levels through L-arginine or L-arginine-rich food can boost nitric oxide bioactivity and bioavailability. This approach can target elevated blood pressure and improve cardiovascular health. Nitric oxide (NO) can be cytotoxic at high concentrations, but its antioxidant effects typically prevail. Moderate consumption of vegan L-arginine-rich proteins may be beneficial for individuals with kidney problems. Older adults and those with cardiovascular and cardiometabolic diseases have an enhanced need for L-arginine and L-arginine-rich proteins to restore and sustain a healthy NO supply.
L-arginine plays a decisive role in preserving brain health, preventing cognitive impairment, and maintaining high NO levels for healthy aging. Aging and age-related cardiovascular diseases lead to arginine and tryptophan depletion, impairing neurovascular coupling. L-arginine and L-tryptophan determine disease development and progression. Supplementation with L-arginine and L-arginine-rich food assures sufficient NO synthesis, neutralizing the age-dependent accumulation of ADMA and the enhanced formation of superoxide anion radicals.
