Nitric Oxide
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Elevated homocysteine levels often slip under the radar during routine checkups, yet they quietly raise our risk...
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Elevated homocysteine levels often slip under the radar during routine checkups, yet they quietly raise our risk...
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The body's ability to generate nitric oxide, a molecule involved in keeping blood pressure under control, falls with age, but providing oral microbes with nitrate-rich foods may help to compensate for this decline by generating more of its precursor, nitrite. Researchers set out to test how age affects responses to nitrate-rich beetroot juice and to antiseptic mouthwash, and whether shifts in oral bacteria explain changes in cardiovascular function.
The trial enrolled 39 younger adults (18–30 years) and 36 older adults (67–79 years). Each person completed three two-week treatment periods. The first two periods followed a randomized double-blind crossover design: all participants received both nitrate-rich and nitrate-depleted beetroot juice in different orders, without knowing which treatment they received. The third period tested antiseptic mouthwash in an open-label format, meaning participants knew which treatment they were given. During each period, researchers assessed blood pressure, blood vessel function, nitric oxide markers in blood and saliva, and shifts in oral microbes.
The findings suggest that age shaped both vascular responses and the oral microbiome:
In both age groups, nitrate-rich juice raised nitrate and nitrite in blood and saliva by about tenfold compared with placebo or mouthwash.
Older adults began with higher blood pressure than younger ones. After nitrate-rich juice, they showed clear reductions, with systolic pressure falling by 7 mmHg and diastolic by 2 to 3 mmHg, while no changes were observed in the younger group.
Nitrate caused a shift in the overall bacterial community in both age groups, but the resulting composition differed by age. Placebo and mouthwash did not alter overall community structure.
Species that support nitrite formation increased, such as Neisseria, while bacteria that divert nitrite away from nitric oxide production declined, including Prevotella and Veillonella. These shifts were stronger in older adults.
Only in young adults, antiseptic mouthwash reduced bacterial diversity and weakened the ability of arteries to widen, although blood pressure did not change.
The findings suggest that nitrate from beetroot juice improved blood pressure in older adults because their oral microbiome shifted toward species that favor nitric oxide production. These microbial shifts may explain the rise in circulating nitrite and the fall in blood pressure seen in older participants. In younger adults, the microbiome shifted in similar ways and plasma nitrite levels rose, but blood pressure remained unchanged. This may reflect that their nitric oxide system was already functioning effectively and, combined with their lower starting blood pressure, left little room for additional benefit from the higher nitrite levels. By contrast, only in the young did mouthwash reduce microbial diversity and impair the arteries' ability to widen. This difference suggests that vascular function in younger adults may depend more on overall microbial diversity, whereas in older adults the key factor was specific compositional changes that influenced nitrite handling. Because the trial relied on genetic markers of bacteria rather than full genomic profiling, always tested mouthwash last, and assessed nitric oxide only indirectly through nitrate and nitrite levels, further studies are needed to confirm these results.
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Breathwork enhances endogenous antioxidant enzyme activity to counter oxidative stress. www.frontiersin.orgVitamin C Mortality Sulforaphane Glutathione Nitric Oxide Antioxidant Oxidative Stress Breathing Technique
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.
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Omega-3s may increase levels of arginine, boosting nitric oxide production. www.nutraingredients-usa.com
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.
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Age-related depletion of nitric oxide synthase cofactors may change the antihypertensive effect of estrogen into a prohypertensive effect. (2005) www.sciencedaily.com
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.
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“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.
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Castration-induced sudden drop in testosterone caused Parkinson's symptoms in mice. (2013) www.sciencedaily.com
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.
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“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.”
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Blood pressure-lowering effect of exercise was diminished by 61% during the 1st hr of recovery when participants were given antibacterial mouthwash. www.sciencedaily.com
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.
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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…
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Taking common non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen for only a week may increase heart attack risk by as much as 50%. www.telegraph.co.uk
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).
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.