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Nitric Oxide

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  • Breathwork has shown promise in ameliorating oxidative stress – a driver of many chronic diseases – in healthy people and those with chronic conditions. However, scientists don’t fully understand the underlying mechanisms that drive these effects. A recent review found that breathwork promotes the activity of endogenous antioxidant enzymes.

    Researchers analyzed the findings of 10 randomized controlled trials (519 participants) investigating the effects of breathwork. The studies encompassed a range of breathwork styles and measured various biomarkers, including malondialdehyde, superoxide dismutase, glutathione, nitric oxide, vitamin C, and total antioxidant capacity levels.

    They found that participants who engaged in breathwork exhibited greater changes in the biomarkers than those who did not. In particular, breathwork increased the activity of the endogenous antioxidant enzymes superoxide dismutase and glutathione activities and decreased levels of malondialdehyde, a marker of oxidative stress.

    Breathwork is an umbrella term that refers to various breathing exercises and techniques. Evidence suggests that breathwork improves heart rate variability and promotes resilience to stress. People often engage in breathwork as part of general relaxation practices, yoga, or meditation.

    These findings suggest that breathwork reduces oxidative stress by promoting the activity of endogenous antioxidant enzymes. Only 10 studies were included in the analysis, however, so more research is needed to support the findings. Sulforaphane, a bioactive compound derived from broccoli, reduces oxidative stress, too. Learn more in this clip featuring sulforaphane expert Dr. Jed Fahey.

  • A new study shows how omega-3 fatty acids increase nitric oxide production – a molecule that supports and enhances athletic performance. Endurance athletes who consumed supplemental omega-3s had higher blood levels of arginine, an amino acid involved in nitric oxide production.

    The study involved 26 men who underwent endurance training for 12 weeks. Half of the men took an omega-3 supplement (approximately 3 grams daily) for the duration of the training, while the other half did not. Researchers measured their Omega-3 Indices and blood amino acid levels before and after the intervention.

    They found that the men who took the supplemental omega-3s had higher Omega-3 Indices than those who did not. These higher indices corresponded with higher blood arginine levels – indirect indicators of increased nitric oxide synthesis and bioavailability.

    Nitric oxide is a molecule produced in the body’s blood vessels and from precursors acquired in the diet via nitrate-containing foods, such as beets and green leafy vegetables. It plays crucial roles in regulating vasodilation, heart rate, and mitochondrial respiration.

    Omega-3s are essential fatty acids that play important roles in cardiovascular health. An abundance of research shows that supplemental omega-3s enhance muscle function and recovery. Learn more about omega-3s in our comprehensive overview article and this episode featuring omega-3 expert Dr. Bill Harris.

    These findings suggest that omega-3 supplementation support nitric oxide production – potentially boosting athletic performance. This was a small study, however, and larger studies are needed to confirm these findings.

  • From the article:

    They were studying estrogen’s effects on blood vessels, focusing on its impact on the smooth muscle cells that allow blood vessels to contract, thereby regulating blood pressure and blood flow. These researchers found that estrogen targets nitric oxide synthase 1, one of three versions of the enzyme that makes the powerful vasodilator, nitric oxide.

    “What we were finding is that estrogen seems to be what you might call a natural nitroglycerin; nitroglycerin also works by making nitric oxide,” Dr. White says.

    Then they tried to block estrogen’s activity by blocking nitric oxide. “What surprised the heck out of me was after we blocked nitric oxide production and added estrogen, we got a contraction,” says Dr. White. “Estrogen now had turned into a constrictor agent, an agent that would increase blood pressure.”

    They looked further and found that normal aging decreases levels of the cofactors L-arginine and tetrahydrobiopterin – both critical to nitric oxide synthase’s production of nitric oxide.

    […]

    “Under normal conditions, such as a pre-menopausal woman, this enzyme, nitric oxide synthase, makes nitric oxide,” says Dr. White. “But if you block the production of nitric oxide, this nitric oxide synthase now has a secondary product that normally isn’t made in an appreciable form. Now it makes a compound called superoxide. It’s an oxidant, and oxidation is bad in general. It causes a lot of cellular damage. But what we also have found is that now, instead of causing relaxation, it causes constriction. So you completely flip-flop the response here.

    “One of the things this means is that menopause is a good thing, a sort of revolutionary endocrinology idea,” says Dr. White.

    View full publication

  • From the article:

    “While scientists use different toxins and a number of complex genetic approaches to model Parkinson’s disease in mice, we have found that the sudden drop in the levels of testosterone following castration is sufficient to cause persistent Parkinson’s like pathology and symptoms in male mice,” said Dr. Kalipada Pahan, lead author of the study and the Floyd A. Davis endowed professor of neurology at Rush. “We found that the supplementation of testosterone in the form of 5-alpha dihydrotestosterone (DHT) pellets reverses Parkinson’s pathology in male mice.”

    “In men, testosterone levels are intimately coupled to many disease processes,” said Pahan. Typically, in healthy males, testosterone level is the maximum in the mid-30s, which then drop about one percent each year. However, testosterone levels may dip drastically due to stress or sudden turn of other life events, which may make somebody more vulnerable to Parkinson’s disease.

    […]

    “This study has become more fascinating than we thought,” said Pahan. “After castration, levels of inducible nitric oxide synthase (iNOS) and nitric oxide go up in the brain dramatically. Interestingly, castration does not cause Parkinson’s like symptoms in male mice deficient in iNOS gene, indicating that loss of testosterone causes symptoms via increased nitric oxide production.”

    View full publication

  • A small randomized placebo-controlled trial finds the blood pressure-lowering effect of exercise was diminished by 61% during the first hour of recovery, and completely abolished 2 hours after exercise when participants were given antibacterial mouthwash.

    Part of the blood-pressure-lowering effect of exercise has to do with increased levels of nitrate and subsequently nitric oxide which causes vasodilatation. When antibacterial mouthwash was given to the participants, their blood nitrite levels did not increase after exercise. It was only when participants used the placebo that nitrite levels in blood raised, suggesting that oral bacteria may play a role in nitrate levels in the circulation at least over the first period of recovery after exercise.

    The antibacterial mouthwash used was 0.2% chlorhexidine. This was a small trial (23 participants) so no definitive conclusions can be made but these results are interesting and should be further explored.

  • You probably already know that ambient light regulates circadian rhythms by interacting with light-sensitive neurons in the eye.

    But let’s review anyway: In full white light (which contains all colors of light), the rays of the blue and green light spectrum activate melanopsin, a photosensitive protein in specific cells of the retina in the back of the eye. When light hits these cells, a signal transmits information to the brain’s master clock. By detecting various intensities and tones of light, the brain can keep track of what time of day it is.

    This is relatively well established. We also know that sunlight can stimulate the production of vitamin D and nitric oxide, both of which have important effects on health. But are these all of the effects that light has on our physiology?

    It has been known for several decades that a small percentage of blue light can penetrate human skin, and can even reach white subcutaneous adipose tissue. But the relevance of this finding on our physiology was not obvious.

    Curiously, it has also been reported that high OPN4 (the gene that encodes the photopigment melanopsin) mRNA levels are found in human subcutaneous fat. Kind of weird: what the heck are these light-sensitive eye proteins doing in our fat tissue? Additionally, we now know that fat cells contain transient receptor potential cation (TRPC) channels – membranes that are found in the retina that open in response to varying intensities of light.

    So, we know that blue light can get to subcutaneous fat tissue, and fat cells seem to have the machinery needed to respond to the signal that is transmitted by light. Very interesting. Is it possible that visible light penetrates the skin, and exerts physiological effects by activating a melanopsin / TRPC channel signaling pathway in human fat? And if so, could exposure to visible light have an impact on the regulation of body fat? The answer appears to be yes.

    My guest in this episode (inadvertently) found the answer to this novel questions…

  • Multiple studies have now linked chronic use of these painkillers with an increased risk of heart attack and stroke. They mechanisms appear to be mediated through the inhibition of an enzyme known as Cox 2. There have been a couple of mechanisms investigated in animal studies. First, NSAIDs have been shown to inhibit the production of a molecule called prostacyclin that relaxes blood vessels and “unglues” platelets. Second, they have been shown to inhibit the production of nitric oxide (which cox 2 also regulates to some degree).

    Other studies have shown that people taking 2 grams of phytosomal curcumin (called Meriva) had pain reduction equivalent to 800 mg of ibuprofen.

    To hear a longer discuss surounding NSAIDS and heart attack risk, as well as the relevance of curcumin in pain-relief make sure to check out JRE#773 or, more recently, Tim Ferriss Show #237 where both topics are discussed.