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In recent years nitric oxide has become a topic of intense discussion. Not to be confused with nitrous oxide (N2O) sometimes referred to as “Laughing Gas”, which is a nonflammable gaseous anesthetic used in dentist’s offices and hospitals.
The discovery of nitric oxide (NO) as a signaling molecule in the body was made in the 1980s by Robert F. Furchgott, Louis J. Ignarro, and Ferid Murad. They were awarded the 1998 Nobel Prize in Physiology or Medicine for their work.
Here are some key milestones in the discovery of nitric oxide:
1620
Belgian scientist Jan Baptista van Helmont first prepared nitric oxide.
1772
English chemist Joseph Priestley first studied nitric oxide and called it "nitrous air".
1970s
Researchers began to understand the role of the endothelium, the innermost layer of blood vessels, in blood vessel contraction and relaxation.
1977
Ferid Murad discovered that nitroglycerin causes the body to produce nitric oxide, which relaxes blood vessels.
1980
Robert Furchgott's "sandwich experiment" demonstrated that the presence or absence of endothelium affects blood vessel contraction and relaxation.
1986
Louis Ignarro concluded that EDRF, an endothelial factor, was identical to nitric oxide. He also discovered that nitric oxide is the neurotransmitter responsible for penile erection.
I have noticed that the topic of nitric oxide is becoming more and more frequent in scientific literature which points to its importance to general health. Sometimes it is difficult for people to ignore the focus on erectile dysfunction as it relates to nitric oxide. This is only natural since things related to sexuality are always a hot topic… No pun intended. The fact is that “sex drive” is inherent in all living species. If it were not, they would become extinct. As humans, our intellect and religious beliefs sometimes act to suppress our natural instincts towards sex. Rest assured, that anything that prevents sexual activity becomes an immediate and serious problem, particularly for men, because testosterone makes them the aggressor by default.
However, it is my objective to demonstrate that the importance of nitric oxide goes far beyond its effect on proper sexual functionality. Nitric oxide (NO) is a naturally occurring molecule in the body that plays a vital role in many physiological processes, including:
Blood circulation
NO helps blood vessels relax and widen, which improves blood flow and lowers blood pressure.
Brain function
NO acts as a neurotransmitter, helping to send messages throughout the body and increasing blood flow to the brain. It also plays a role in learning, perception of pain, and regulation of gene expression.
Immune system
NO helps control and communicate with immune cells, helping them to react more quickly to invaders. It also has antibacterial, antifungal, and antiviral properties.
Digestive system
NO controls the smooth muscles in the gastrointestinal tract, helping to move food out of the body.
Respiratory system
NO helps relax the airways, which can be helpful for breathing diseases like asthma.
Renal system
NO increases blood flow to the kidneys, which helps with urination.
Muscle function
NO modulates muscle contraction and cell function and is involved in cell-cell interactions.
Low levels of nitric oxide can increase the risk of high blood pressure, coronary artery disease, impaired vision, depression, and cognitive decline
The Importance of Nasal Breathing and Nitric Oxide Production
The exact origin of the NO found in nasal air and the relative contribution from different sources within the nasal airways are not known. There are, however, some indications that favor the paranasal sinuses rather than the mucosa of the nasal cavity as a major source of nasal NO in adult healthy humans.
In 1998, The Nobel Peace Prize was awarded jointly to Robert F. Furchgott, Louis J. Ignarro and Ferid Murad. The title of the Nobel Prize was “Nitric Oxide as a Unique Signaling Molecule in the Cardiovascular System.” Today, it is recognized that NO is a widespread signaling molecule in all organs of the body, not only the cardiovascular system.
Nasal breathing improves lung health and oxygenation of the body in several ways. The nose helps to filter particulate matter that can adversely affect the health of the lungs and contribute to inflammation. Breathing through the nose significantly reduces particle deposition in the lungs that occurs during mouth breathing. Nasal breathing also improves pulmonary function by improving the motility of the cilia. It also improves the circulation in the lungs so that the blood is better oxygenated by around 10%.
Humming increases nitric oxide levels in the nose by causing air to oscillate, which speeds up the exchange of air between the sinuses and the nasal cavity. The paranasal sinuses are major producers of NO, and humming can increase nasal NO levels by up to 15-fold.
Try humming to increase nitric oxide:
Close your mouth and breathe through your nose
Place the tip of your tongue behind your top front teeth
Exhale slowly through your nose while making a sustained "hmmmmmm..." sound
Gently massage your sinuses
Nitric oxide is produced naturally by the human body and is one of the most important molecules for blood vessel health. It’s a vasodilator, meaning it relaxes the inner muscles of your blood vessels, causing the vessels to widen. In this way, nitric oxide increases blood flow and lowers blood pressure.
How to Increase Nitric Oxide in Your Body (click to view)
Normal vs. Dilated Blood Vessels
The image above shows the same blood vessel before and after the effect of nitric oxide on the endothelial cells that line the inside of blood vessels, this action has the effect of lowering blood pressure and lowering the chance of blood clots.
Supplements that increase nitric oxide in the body make up one of the most popular supplement categories today. These supplements don’t contain nitric oxide itself. However, they contain compounds that your body can use to make nitric oxide and have been shown to provide many benefits for health and performance.
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Beets
Beets are rich in dietary nitrates, which your body can convert to nitric oxide. Thanks to their rich content of dietary nitrates, beets have been linked to a number of health benefits, including improved thinking ability, enhanced athletic performance, and lower blood pressure levels.
Garlic
Garlic can boost nitric oxide levels by activating nitric oxide synthase, the enzyme that helps convert the amino acid L-arginine to nitric oxide.
Meat
Meat, poultry, and seafood are all excellent sources of coenzyme Q10 (CoQ10), an important compound that is believed to help preserve nitric oxide in the body.Organ meats, fatty fish, and muscle meats such as beef, chicken and pork contain the highest concentration of CoQ10.
Dark Chocolate
Dark chocolate is loaded with flavanols, naturally occurring compounds that boast an extensive list of powerful health benefits.
Leafy Greens
Leafy green vegetables such as spinach, arugula, kale, and cabbage are packed with nitrates, which your body converts to nitric oxide.
Citrus Fruit
Citrus fruits such as oranges, lemons, limes, and grapefruit are all excellent sources of vitamin C, an important water-soluble vitamin that plays a central role in health.
Pomegranate
Pomegranate is loaded with potent antioxidants that can protect your cells against damage and preserve nitric oxide.
Nuts and Seeds
Nuts and seeds are high in arginine, a type of amino acid that is involved in nitric oxide production.
Watermelon
Watermelon is one of the best sources of citrulline, an amino acid that your body converts first to arginine and then to nitric oxide.
Red Wine
Red wine contains many powerful antioxidants and has been linked to some health benefits.
Interestingly, some studies have found that drinking red wine could also increase nitric oxide levels.
Blood pressure: NO helps blood vessels relax and widen, which improves blood flow and lowers blood pressure.
Heart health: NO can help protect against heart problems and cardiovascular disease.
Exercise performance: NO can improve endurance, reduce inflammation and fatigue, and help muscles repair and grow.
Immune system: NO helps the immune system respond to infection and inflammation.
Nervous system: NO helps send messages throughout the body, including to the brain, and aids erectile function.
Digestive system: NO controls the smooth muscles in the gastrointestinal tract and helps move poop out of the body.
Respiratory system: NO helps relax the airways and prevents them from becoming very restricted.
Brain health: NO can support brain health.
Nitric oxide (NO) is a signaling molecule that plays a vital role in vascular health and the cardiovascular system:
Vasodilation: NO acts as a vasodilator, opening up blood vessels to improve blood flow and blood pressure
Platelet aggregation: NO prevents platelets from aggregating and sticking to the endothelium
Inflammation: NO has anti-inflammatory properties
Atherosclerosis: NO inhibits the atherosclerotic process
Myocardial contractility: NO regulates myocardial contractility
When there isn't enough NO in the blood vessel walls, it's called endothelial dysfunction. This can lead to a number of problems, including: Narrowed blood vessels, High blood pressure, Inflammation in the artery walls, Increased platelet production, and porous blood vessel walls.
Reduced bioavailability of NO is thought to be a central factor in cardiovascular disease. However, it's not clear if this is the cause or result of endothelial dysfunction.
Since the discovery of nitric oxide deficiency as a cause of erectile dysfunction there has been a great deal of interest in supplements and medications that can be used to increase available nitric oxide in the bloodstream. Following are a number of supplements that have been proven effective and safe for nitric oxide supplementation:
L-arginine
May improve ED by increasing blood flow to the penis. However, it can cause side effects like nausea, cramps, and diarrhea. You should not take L-arginine with sildenafil (Viagra).
Ginseng
A study found that Panax ginseng improved sexual function in men with ED. However, it can cause side effects like insomnia, headaches, and vertigo.
Propionyl-L-carnitine
When combined with Viagra, propionyl-L-carnitine may improve erectile function. It is likely safe when used under medical supervision.
DHEA
May increase libido in women and help with ED in men. It appears to be safe at low doses, but it can cause acne.
Fenugreek
Also known as “methi,” fenugreek may increase sexual arousal and orgasm.
Ginkgo
May improve circulation by increasing nitric oxide levels in the blood.
Other supplements that may help with ED include:
Vitamin B2, B3, B6, and D3
Vitamin K
Zinc
Pycnogenol
Yohimbe /yohimbine
Tribulus terrestris
Eurycoma longifolia (tongkat ali)
Research into vitamins and supplements to treat ED is still in its early stages, and more research is needed. You should talk with a healthcare professional before trying supplements to help with ED.
The Food and Drug Administration (FDA) approved Viagra (sildenafil) for use as an oral treatment for erectile dysfunction (ED) on March 27, 1998. Despite the drug’s popularity today, the researchers who discovered it weren’t even looking for it. Sildenafil, the active ingredient in Viagra, was originally developed to treat cardiovascular problems. It was meant to dilate the heart’s blood vessels by blocking a particular protein called PDE-5. In animal tests, it seemed to work moderately well: researchers could find evidence that it was impeding PDE-5, and the animals weren’t having any obvious negative side effects. So, it was brought into a phase one clinical trial in the early 1990s, to test whether humans can tolerate a new compound.
Cialis, also known by its generic name tadalafil, was discovered in the early 1990s and approved by the FDA in the United States on November 21, 2003. Like Viagra, Cialis is a phosphodiesterase inhibitor. In 2011 approved for the treatment of benign prosthetic hyperplasia (BPH), commonly referred to as prostate enlargement. This condition leads to frequent urination, particularly common in older men. At 51 to 60 years old about 50% of men are affected. After age 70 more than 80% of men suffer from BPH. Tadalafil offers excellent control and maintenance for this condition. Tadalafil is also used to treat pulmonary arterial hypertension (PAH).
The maximum doses of tadalafil for each of its approved uses are as follows:
ED: 20 mg as needed before sexual activity
BPH: 5 mg once daily
PAH: 40 mg once daily
Before leaving this category, I would like to mention that while Viagra and Cialis have demonstrated their effectiveness in treating ED, particularly in younger men, their efficacy declines in proportion to advancing age possibly requiring increased dosage to produce the same effect. For this reason, the use of Viagra (sildenafil) or Cialis (tadalafil) should be closely monitored because their effect can vary widely on older individuals. Also, Cialis has a significantly longer half-life as compared to Viagra and therefore can remain effective for 36-hours.
Please keep in mind that neither of these medications increase sexual desire or libido. Their main benefit is increased blood flow to the genital region for both males and females. However, recent research has discovered that a particular class of peptides can effectively treat “low sex drive” in both men and women. These naturally occurring amnio acids work directly on the brain to increase libido. The best known of these is PT-141. In June of 2019 the FDA approved this peptide, now named Vyleesi to treat hypoactive sexual desire disorder (HSDD) in premenopausal women. Although still considered “off-label” for men, it has shown to be effective for older men without significant side effects once proper dosage has been established.
Many men complain that Viagra or Cialis takes much longer to take effect then they were told or that they would like. This in turn makes it very difficult to coordinate the time of taking the medication and the ideal time for intercourse. Part of this problem may be related to food, with respect to scheduling and types of meals. As Dr. Malik indicated in her podcast, high-fat meals reduce the effect of both Viagra and Cialis, and in some cases may prevent the medication from working at all. Fortunately, there is a recent development that may help in both these cases…Sublingual ED medications.
Sublingual medications are not pills intended to be swallowed. Instead, these medications are placed under the tongue and absorbed into the blood through the mouth’s tissues. The space under the tongue has many tiny blood vessels (capillaries). The capillaries allow you to absorb the medication directly into your bloodstream…It’s like getting a shot, but without the needle. The end result is they work much faster and may require lower dosages and are not effected by large meals. You must specially ask for these newer options.
Until next time, take care and stay positive… Dr. G
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