Newsletter #277

Hey friends, this week I wanted to dive into a new study examining the effect of dietary nitrates on brain health — and the importance of the context in which they are consumed.

Nitrates are found naturally in a range of edible plants, like beets and leafy greens such as spinach and arugula. When we consume nitrates, they act as precursors to nitric oxide (NO), which in turn relaxes and widens the walls of blood vessels, enhancing blood flow and lowering blood pressure.

This is obviously beneficial for vascular health in general, and cohort studies have found that consuming a diet richer in nitrate is associated with lower cardiovascular risk. It also seems to be particularly helpful for the brain, which relies upon a healthy blood supply for proper function. For instance, a study that compared a high-nitrate to a low-nitrate diet in older adults found that the higher nitrate diet resulted in increased blood flow in areas of the brain that are involved with executive functioning.

You might wonder, then: why can’t we just use nitrate in a pill to efficiently elevate levels of nitric oxide?

The answer, it seems, is that taking sodium nitrate in isolation is not very effective when compared to consuming nitrates in a food matrix. For instance, when researchers had subjects ingest 800 mg of nitrate in the form of fresh vegetables, levels of plasma nitrate and nitrite increased and blood pressure reliably declined. But when the same participants consumed 800 mg of nitrate from sodium nitrate (NaNO3), they did not observe the same benefits. And when trained athletes drank beetroot juice, they performed better at high-intensity cycling, but failed to see improvements in oxygen consumption when they attempted the same trial using sodium nitrate.

Why is this?

It has been hypothesized that other naturally occurring compounds in vegetables may have important synergistic effects when co-ingested with nitrate. We know, for instance, that reactive oxygen species (ROS) can scavenge nitric oxide. Could antioxidant compounds in plants combat ROS, and thus boost bioavailability of NO? And could this explain why a diet rich in vegetables (especially green leafy) is associated with reduced risk of neurodegeneration?

To explore potential interactions between vitamin C and inorganic nitrate, researchers in the UK recruited ten younger (29 ± 1 years) and ten older (62 ± 1 years) participants in Newcastle, and had them visit the laboratory on four different occasions. On each visit, they were given a solution of 1) potassium nitrate, 2) vitamin C, 3) potassium nitrate + vitamin C, and 4) placebo. Over a three hour period, resting blood pressure and various indices of vascular function were monitored.

Nitrate supplementation alone did not influence blood pressure or vascular function significantly. However, in the older participants, combined supplementation with nitrate and vitamin C resulted in a decrease in mean arterial blood pressure (−2.6 mmHg), as well as a decrease in pulse wave velocity. Pulse wave velocity is a clinical measure of arterial stiffness. Generally, as people get older, blood vessels stiffen, and the pressure waves of blood travels faster through arteries, which can lead to damage to the blood vessels as well as pathological remodeling of the heart. Vitamin C by itself also improved pulse wave velocity, to a lesser degree, and decreased blood pressure in older adults.

So, this trial certainly seems to suggest that nitrates need to be consumed with dietary antioxidants in order to work their magic, and vascular improvements are most likely to be evident in people who are starting out with a worse baseline (i.e. older adults).

To examine how nitrate in the diet correlates with risk of dementia, researchers analyzed data from the Rotterdam Study, a large prospective population-based cohort. Between 1990-2009, dietary intake was assessed in 9543 older adults in the Netherlands who did not have dementia at the start of the study. Subjects were then followed until January 2020 (a mean followup of 14.5 years).

The researchers determined that higher intake of dietary nitrate from vegetables, but not from non-vegetable sources, was associated with a lower risk of going on to develop dementia. Specifically, every 50-mg per day increase in dietary nitrate was linked to an 8% reduction in risk. To put that amount into perspective, excellent sources of nitrate are arugula (~480 mg per 100 g) and beet juice (~280 mg per 100 mL).

The researchers suggest that when nitrate is consumed from non-vegetable sources, without antioxidant compounds naturally occurring in vegetables, it is more likely to be converted to nitrosamines, which are potentially carcinogenic and have been implicated in neurodegeneration. However, it is worth noting here that nitrates from non-vegetable sources would have primarily come from foods that are high in sodium and saturated fat (such as processed meats). In other words, non-vegetable sources of nitrates may have been associated to poorer outcomes simply because they were bound to unhealthy foods.

In any case, if you're hoping to maximize the benefits of dietary nitrate, it probably makes sense to acquire them from fresh whole foods, like arugula and spinach — or from concentrated beetroot juice if you are looking for efficiency.

We now know that oral bacteria play a central role in nitric oxide homeostasis, through the salivary nitrate-nitrite-nitric oxide pathway. When dietary nitrate is absorbed through the small intestine and enters systemic circulation, some of it is taken up by the salivary glands. Nitrate-reducing oral bacteria reduce that nitrate to nitrite, which is swallowed and then absorbed again, where it undergoes further reduction to nitric oxide.

Much like antibiotics can result in perturbations of the gut microbiota, antibacterial mouthwash can disrupt oral flora, and in turn interfere with the proper functioning of this pathway.

For instance, one trial found that using chlorhexidine mouthwash for seven days led to a 90% reduction in oral nitrite production and a 25% reduction in plasma nitrite levels. In the volunteers, these shifts in nitrite were correlated with a significant increase in blood pressure, suggestive of a clinically meaningful inhibition of the salivary nitrate-nitrite-nitric oxide pathway.

Of course, this is unfortunate if you are an athlete who is relying on nitrate supplements, like beetroot juice, for ergogenic purposes. But it may also have serious health implications.

Multiple meta-analyses over the years have found that the use of such mouth rinses is associated with higher mortality rates in hospitalized patients, and it has been hypothesized that disruption of the nitrate–nitrite–nitric oxide pathway may explain this otherwise perplexing relationship.

Beet It delivers ~400 mg of nitrate per serving in a portable 2.4 ounce shot. So this is definitely the fastest and easiest way to get your nitrates!

Furthermore, Beet It is what many researchers, including Jonathan Burdette at Wake Forest, have used to examine effects of dietary nitrate (check out our interview with him), so you can be assured that this product will be effective.

Optimizing Nutrition with Smoothies

This week, we’d like to highlight our course on smoothies and phytochemicals.

The course takes a deep dive into phytochemicals in plants, their powerful health effects, and how intelligently-devised smoothies can help optimize our intake of these compounds.

For more practical information on using smoothies to enhance nutrition, please refer to our How-to Guide for smoothies.

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