Nitric Oxide: The Fountain of Youth?
Nitric oxide (NO) is a gaseous signaling molecule that plays a crucial role in various physiological processes within the human body. It is produced by cells in different tissues and organs, and its functions are diverse.
Maintaining a balance in nitric oxide production is essential for overall health. Too little NO can lead to issues such as hypertension and impaired blood flow, while excessive production is associated with inflammation and oxidative stress. Factors such as age, lifestyle choices, and underlying health conditions can influence NO levels in the body.
Maintaining healthy levels of NO as we age prolongs longevity. However, the production and bioavailability of NO decreases with age. By the age of 40, most individuals produce about 50% less NO than they produced as a youth and 85% less by the age of 60.
Several factors contribute to this decline:
Endothelial Dysfunction:
Nitric oxide is primarily produced by endothelial cells that line the inner walls of blood vessels. With aging, these endothelial cells may become less efficient, leading to endothelial dysfunction.
Dysfunction in endothelial cells can impair the synthesis and release of nitric oxide, reducing its availability for vasodilation and other physiological functions.
Reduced Nitric Oxide Synthase (NOS) Activity:
Nitric oxide is synthesized by enzymes called nitric oxide synthases (NOS), with endothelial NOS (eNOS) being particularly important for vascular function.
Age-related changes may lead to decreased NOS activity, resulting in lower NO production.
Increased Oxidative Stress:
Aging is associated with an increase in oxidative stress, which occurs when there is an imbalance between the production of reactive oxygen species (ROS) and the body's ability to neutralize them.
Elevated oxidative stress can damage cells, including endothelial cells, and compromise NO production.
Inflammation:
Chronic inflammation, which tends to increase with age, can negatively impact nitric oxide synthesis and function.
Inflammatory processes can disrupt the normal regulation of nitric oxide, contributing to decreased NO levels.
Reduced Availability of Substrates:
Nitric oxide is synthesized from the amino acid arginine. Age-related changes in the availability of arginine or other cofactors necessary for nitric oxide production may contribute to decreased NO levels.
Genetic Factors:
Genetic factors can influence the regulation of NO production, and some individuals may be more predisposed to age-related declines.
Lifestyle Factors:
Unhealthy lifestyle choices, such as poor diet, lack of exercise, mouthwash usage, and smoking, can contribute to endothelial dysfunction and reduce NO levels.
Oral Microbiome:
Individuals with a higher abundance of oral nitrate-reducing bacteria have higher salivary nitrite production.
Antimicrobial/antiseptic mouthwashes will lower healthy nitrate-reducing oral bacteria.
Medications:
Medications that can lower NO include antibiotics, SSRIs, NSAIDs, oral contraceptives, and PPIs.
Stress:
Cortisol production increases with low NO.
The adrenal glands also need NO to function effectively.
Hormonal Changes:
Changes in hormone levels, including reduced estrogen in postmenopausal women and declining levels of certain hormones with aging, can influence NO synthesis.
Women with low levels of NO have been shown to have worse menopausal symptoms.
The increase in cardiovascular risk seen in menopausal women is likely due to a decrease in NO.
Hormone replacement therapy has been shown to increase NO levels in post-menopausal women.
Nitric oxide exerts a wide range of physiological effects in the human body, influencing various systems and processes. Here are some key physiological effects of nitric oxide:
Vasodilation:
Nitric oxide is a potent vasodilator, meaning it relaxes the smooth muscles in blood vessel walls, leading to the dilation of blood vessels.
This effect helps regulate blood flow, reduce blood pressure, and improve oxygen and nutrient delivery to tissues.
Blood Pressure Regulation:
Nitric oxide plays a crucial role in the regulation of blood pressure by modulating the tone of blood vessels.
It helps maintain normal blood pressure by promoting vasodilation and preventing excessive vasoconstriction.
Neurotransmission:
Nitric oxide serves as a neurotransmitter in the central nervous system, contributing to the communication between nerve cells.
It plays a role in synaptic plasticity, which is essential for learning and memory.
Immune System Modulation:
Nitric oxide is involved in the immune response, influencing the function of immune cells.
It can act as a signaling molecule in the immune system, contributing to the body's defense against pathogens.
Anti-Inflammatory Effects:
Nitric oxide has anti-inflammatory properties and can help modulate the immune response to control inflammation.
It may play a role in resolving inflammation and preventing chronic inflammatory conditions.
Platelet Function Regulation:
Nitric oxide helps regulate platelet function, preventing excessive blood clotting and reducing the risk of thrombosis.
Endothelial Health:
Nitric oxide is produced by endothelial cells lining blood vessels, contributing to the maintenance of endothelial health.
It supports the integrity and function of the endothelium, which is crucial for cardiovascular health.
Muscle Function and Exercise Performance:
Nitric oxide is involved in the regulation of blood flow to muscles during exercise, contributing to improved exercise performance and recovery.
It may enhance nutrient and oxygen delivery to active muscles.
Mitochondrial Function:
Nitric oxide can influence mitochondrial function, impacting energy production within cells.
Wound Healing:
Nitric oxide plays a role in the process of wound healing, contributing to tissue repair and regeneration.
It also has antimicrobial properties.
Gastrointestinal Function:
Nitric oxide is involved in regulating smooth muscle relaxation in the gastrointestinal tract, influencing processes such as digestion and peristalsis.
Loss of nitric oxide is often one of the earliest events in the onset of several chronic diseases. Early signs and symptoms of NO loss include elevated blood pressure, sexual dysfunction, exercise intolerance, insulin resistance, and memory disturbances.
NO supplementation is an area of research with potential therapeutic applications, particularly in conditions where improving blood flow, reducing inflammation, or enhancing cardiovascular function may be beneficial. It's important to note that while some studies suggest potential benefits, more research is needed to establish the effectiveness of NO supplementation in specific diseases. Here are some conditions where NO supplementation is being investigated:
Cardiovascular Diseases:
Hypertension (High Blood Pressure): NO is a vasodilator that helps relax blood vessels, potentially contributing to lower blood pressure. Some studies suggest that NO supplementation may have a positive impact on blood pressure regulation.
Atherosclerosis: NO is involved in preventing the formation of arterial plaques. NO supplementation may support vascular health and reduce the progression of atherosclerosis.
Erectile Dysfunction:
NO plays a key role in the regulation of blood flow to the erectile tissue. Medications that increase NO levels, such as phosphodiesterase type 5 (PDE5) inhibitors like sildenafil (Viagra), are commonly used to treat erectile dysfunction.
NO has also been shown to improve sexual response in women.
Raynaud's Disease:
Raynaud's disease is characterized by reduced blood flow to certain parts of the body, typically the fingers and toes, in response to cold or stress. NO supplementation may help improve blood flow and alleviate symptoms.
Heart Failure:
Some studies suggest that NO supplementation may have potential benefits in heart failure by improving cardiac function and exercise tolerance.
Respiratory Conditions:
Pulmonary Hypertension: NO is used as a treatment for pulmonary hypertension, a condition characterized by increased blood pressure in the arteries of the lungs. Inhaled NO can help dilate the pulmonary blood vessels.
Chronic Obstructive Pulmonary Disease (COPD): NO supplementation is being explored for its potential to improve lung function and reduce inflammation in COPD patients.
Diabetes:
Diabetes is associated with endothelial dysfunction and impaired NO production. Some studies suggest that NO supplementation may have a positive impact on vascular health in individuals with diabetes.
Inflammatory Conditions:
NO has anti-inflammatory properties, and its supplementation is being investigated for conditions involving inflammation, such as rheumatoid arthritis.
Neurological Disorders:
NO is involved in neurotransmission and may have neuroprotective effects. Research is ongoing to explore the potential role of NO supplementation in conditions like Alzheimer's disease and Parkinson's disease.
Nitric oxide has also been shown to play a role in pre-eclampsia, glaucoma, asthma, and skin conditions (eczema, acne, aging skin).
It's important to approach NO supplementation with caution, as excessive levels of NO can have detrimental effects and contribute to oxidative stress. Additionally, individual responses to NO supplementation may vary, and potential benefits should be weighed against possible risks.
Before considering NO supplementation, especially in the form of dietary supplements, individuals should consult with healthcare professionals to discuss potential benefits and risks, taking into account their specific health conditions and medications.
Nutrition & Nitric Oxide
Certain foods contain nutrients that can support the production of NO in the body or provide precursors essential for its synthesis. Including these foods in your diet may help promote NO production. Here are some foods that are known to support NO production:
Beets and Beetroot Juice:
Beets are rich in nitrates, which can be converted into NO in the body. Beetroot juice, in particular, has been associated with increased NO levels.
Leafy Greens:
Vegetables such as spinach, kale, and arugula are high in nitrates and may contribute to NO production.
Garlic:
Garlic contains allicin, a compound that may help increase NO production and promote blood vessel dilation.
Citrus Fruits:
Citrus fruits like oranges and grapefruits contain antioxidants, vitamin C, and flavonoids that may support NO activity.
Pomegranate:
Pomegranates and pomegranate juice have been associated with increased NO levels and improved cardiovascular health.
Watermelon:
Watermelon contains citrulline, an amino acid that can be converted into arginine, a precursor for NO synthesis.
Nuts and Seeds:
Nuts and seeds, such as almonds and sunflower seeds, are good sources of arginine, which is involved in NO production.
Dark Chocolate:
Dark chocolate contains flavonoids that may stimulate NO production and promote vascular health.
Fish:
Fatty fish, like salmon and mackerel, are rich in omega-3 fatty acids, which have been associated with improved endothelial function and NO production.
Whole Grains:
Whole grains, such as oats and quinoa, contain arginine and may support NO synthesis.
Turmeric:
The active compound in turmeric, curcumin, has antioxidant and anti-inflammatory properties that may positively influence NO production.
Green Tea:
Green tea contains catechins, which may contribute to improved NO bioavailability and cardiovascular health.
Red Wine:
Resveratrol, a compound found in red wine, may have vasodilatory effects, and support NO production. However, moderation is key due to alcohol content.
Several nutrients play a role in supporting and enhancing nitric oxide production in the body. These nutrients are involved in various pathways related to NO synthesis. Here are some key nutrients that may help increase NO production:
L-Arginine:
L-arginine is an amino acid that serves as a precursor for NO synthesis.
It is a substrate for the enzyme nitric oxide synthase (NOS), which converts L-arginine into NO.
L-Citrulline:
L-citrulline is another amino acid that can be converted into L-arginine in the body.
It indirectly supports NO production by increasing arginine levels.
Nitrates and Nitrites:
Certain foods, such as beets, leafy greens, and some root vegetables, contain nitrates.
The consumption of nitrate-rich foods increases NO in the body independent of NOS enzymatic function. The body can convert dietary nitrates into nitrites and then into NO.
Antioxidants:
Antioxidants, such as vitamins C and E, help protect NO from being broken down by reactive oxygen species (ROS).
By reducing oxidative stress, antioxidants support the stability and availability of NO.
Polyphenols:
Polyphenols found in foods like berries, tea, dark chocolate, and red wine have been associated with increased NO production.
They may enhance endothelial function and promote NO synthesis.
Garlic:
Garlic contains allicin, a compound that has been suggested to increase NO production.
Garlic may also have other cardiovascular benefits.
Omega-3 Fatty Acids:
Omega-3 fatty acids, found in fatty fish and flaxseeds, may support NO production.
They have been associated with improved endothelial function.
Coenzyme Q10 (CoQ10):
CoQ10 is involved in the electron transport chain in mitochondria and may have a role in supporting NO production.
It also possesses antioxidant properties.
Vitamin D:
Vitamin D has been linked to improved endothelial function and NO synthesis.
Adequate vitamin D levels may be beneficial for cardiovascular health.
Magnesium:
Magnesium is a mineral that is involved in the activation of nitric oxide synthase (NOS).
It may support the production of NO in the body.
Folate (Vitamin B9):
Folate is involved in the conversion of L-arginine to NO.
It plays a role in the activity of endothelial NOS (eNOS).
Lifestyle & Nitric Oxide
Several lifestyle changes can positively influence nitric oxide production in the body. Here are some strategies to naturally boost NO levels:
Regular Exercise:
Engage in regular physical activity, as exercise stimulates the production of NO. Both aerobic exercise and resistance training have been shown to positively influence NO levels.
Sunlight Exposure:
Exposure to sunlight can increase NO production through the skin. Aim for safe sun exposure to promote the synthesis of vitamin D, which plays a role in NO production.
NO levels are lower in winter than summer months.
Far infrared saunas have been shown to increase NO.
Hydration:
Stay adequately hydrated, as dehydration can impair NO synthesis. Water is essential for the production and function of NO in the body.
Maintain Healthy Blood Pressure:
High blood pressure can negatively impact NO production. Adopting a heart-healthy lifestyle, including a balanced diet, regular exercise, and stress management, can help maintain healthy blood pressure.
Adequate Sleep:
Ensure you get enough quality sleep, as sleep deprivation may reduce NO levels. Aim for 7-9 hours of sleep per night to support overall health.
Decreased NO with aging is associated with impaired circadian rhythm.
NO increases and regulates REM sleep.
Manage Stress:
Chronic stress can negatively affect NO production. Practice stress management techniques such as meditation, deep breathing exercises, yoga, or other relaxation methods.
Moderate Alcohol Consumption:
Excessive alcohol intake can impair NO synthesis. If you consume alcohol, do so in moderation to support overall health.
Avoid Tobacco Products:
Smoking and the use of tobacco products can adversely affect NO levels. Quitting smoking is a crucial step in promoting cardiovascular health and NO production.
Nitric Oxide and the Organic Conundrum
Many factors contribute to the effectiveness of nitrate rich vegetables on the cardiovascular system. Those factors include the region in which the produce is grown, the soil quality, amount of sunlight, time of harvest, and perhaps most importantly, the amount of nitrogen in the soil.
Organic farmers, like any others, need to provide enough nitrogen (N) for crops to maintain good yields, product quality and profitability. But unlike conventional farmers, organic farmers rarely rely primarily on bagged N fertilizers.
Organic produce has been shown to have considerably less nitrate than conventionally grown produce.
Difference between Plant & Meat Nitrites
Nitrites are compounds that can be found in both plant-based and animal-based foods. Nitrites in plant-based foods come from the plant itself, which often has other beneficial nutrients and compounds, such as antioxidants and fiber.
In processed meats, nitrites are added as preservatives at higher levels. Nitrites can react with compounds naturally present in meat, such as amines, to form nitrosamines. Nitrosamines are known to be potentially carcinogenic.
The World Health Organization has classified processed meat as a Group 1 carcinogen. This is in the same category as tobacco.
Several studies have linked the consumption of processed meats containing added nitrites with an increased risk of several health issues. These include cancer (particularly colorectal) and cardiovascular disease.