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S7

Also known as: Inorganic nitrate, Nitrate, Nitric oxide boosters, Sodium nitrate, Potassium nitrate, Inorganic Nitrate

Overview

Inorganic nitrates are compounds containing the nitrate ion (NO3^-), naturally abundant in leafy green vegetables like spinach and beetroot. As a supplement, nitrates are used to enhance athletic performance and improve cardiovascular health by increasing nitric oxide (NO) levels in the body. Nitrates convert to nitric oxide, a potent vasodilator, improving blood flow and oxygen delivery to tissues. Research on nitrate supplementation is moderately mature, with numerous systematic reviews and meta-analyses available. However, the evidence is mixed, with some studies showing positive effects and others indicating trivial or statistically insignificant results. The quality of evidence is often limited by small sample sizes and heterogeneity among studies. Supplement forms include beetroot juice, nitrate-rich foods, and nitrate salts like sodium or potassium nitrate.

Benefits

The benefits of nitrate supplementation are mixed, with some studies showing positive effects while others indicate trivial or statistically insignificant results. A systematic review and meta-analysis found statistically non-significant effects on aerobic performance, maximal time to exhaustion (TTE), submaximal TTE, VO2 peak, and 6-minute walking distance in clinical populations, particularly those with cardiovascular diseases (CVD). However, another systematic review and meta-analysis indicated a statistically significant improvement in maximum walking distance when using fixed-effect models, although this was influenced by studies with some risk of bias. Benefits appear more pronounced in populations with peripheral artery disease (PAD), where antioxidant interventions (including nitrates) showed significant improvements in walking distances. Effect sizes are generally small to trivial, with standard mean differences (SMDs) often below 0.2, indicating minimal clinical significance in many outcomes.

How it works

Inorganic nitrates are converted to nitric oxide (NO) in the body, primarily through the nitrate-nitrite-nitric oxide pathway. NO acts as a vasodilator by stimulating the production of cyclic guanosine monophosphate (cGMP) in vascular smooth muscle cells, leading to blood vessel relaxation and increased blood flow. The primary interaction is with the cardiovascular system, where increased NO levels can improve blood flow and reduce blood pressure. The key molecular target is soluble guanylate cyclase, which is activated by NO to produce cGMP. Nitrates are generally well-absorbed from the gastrointestinal tract and rapidly converted to NO in the body.

Side effects

Nitrates are generally considered safe when used in recommended doses, but high doses can lead to adverse effects. Common side effects include headache, dizziness, and gastrointestinal upset, particularly at higher doses. Uncommon side effects include flushing, palpitations, and orthostatic hypotension. Rare side effects include severe hypotension, methemoglobinemia, and allergic reactions. Nitrates can interact with phosphodiesterase inhibitors (e.g., sildenafil), leading to severe hypotension. They are contraindicated in patients with severe hypotension, acute myocardial infarction, and those taking certain medications like phosphodiesterase inhibitors. Caution is advised in pregnant or breastfeeding women, as well as in patients with certain cardiovascular conditions.

Dosage

The minimum effective dose is not well-established but typically ranges from 500 mg to 2 grams of nitrate per day. Optimal dosages vary but are often in the range of 1-3 grams per day, depending on the specific health outcome being targeted. The maximum safe dose is generally considered to be around 4-6 grams per day, though this can vary based on individual tolerance and health status. Timing can vary; some studies use acute doses before exercise, while others use subacute or chronic supplementation models. Nitrates can be taken in various forms, including beetroot juice, nitrate-rich foods, or supplements like sodium nitrate or potassium nitrate. Absorption is generally good but can be influenced by dietary factors and individual variability.

FAQs

How long does it take to see benefits from nitrate supplementation?

Benefits can be seen acutely or after several days of supplementation, depending on the individual and the specific outcome being measured.

Are nitrates safe for everyone?

Generally safe, but caution is advised in certain populations, such as those with hypotension or those taking phosphodiesterase inhibitors.

How should nitrates be taken?

Can be taken as supplements, foods, or beverages, with timing varying based on the desired effect, such as before exercise or as part of a daily regimen.

What are the common side effects of nitrate supplementation?

Headache, dizziness, and gastrointestinal upset are common, particularly at higher doses.

Do nitrates always improve athletic performance?

No, the evidence is mixed, and benefits are not universal. Individual responses can vary.

Research Sources

https://www.mdpi.com/2072-6643/16/22/3832 – This systematic review and meta-analysis examined the ergogenic effects of nitrate supplementation in clinical populations. The study found trivial effects on aerobic performance, maximal time to exhaustion, submaximal time to exhaustion, VO2 peak, and 6-minute walking distance. The authors noted that heterogeneity and small sample sizes limit the significance of the findings.
https://www.dec.gov.ua/wp-content/uploads/2019/11/global-evidence-summit-abstracts-2017.pdf – This abstract from the Global Evidence Summit discusses the impact of dietary supplements on nitric oxide levels. It highlights a statistically significant improvement in maximum walking distance in the intervention group, particularly with antioxidant interventions. However, the quality of evidence is affected by the risk of bias in included studies.
https://www.mdpi.com/2227-9059/11/7/1859 – This study investigates the effects of plant-based supplements on nitric oxide production. It provides insights into how certain plant-derived compounds can enhance nitric oxide levels, potentially leading to improved cardiovascular function and exercise performance. The research emphasizes the importance of understanding the mechanisms and efficacy of these natural supplements.
https://iris.who.int/bitstream/handle/10665/364094/1020-3397-2022-2809-635-701-eng.pdf?isAllowed=y&sequence=1 – This document from the World Health Organization discusses various aspects of nutrition and health. While it may not directly focus on nitrate supplementation, it provides valuable context on dietary guidelines and the importance of a balanced diet for overall well-being, which can indirectly influence the effectiveness of supplements like nitrates.
https://vaneeghen.com/insights/128/vaneeghen.com/insights/128/s7-plant-based-and-clinically-proven-to-increase-nitric-oxide-no-by-230 – This article promotes a plant-based supplement (S7) and claims it is clinically proven to increase nitric oxide levels by 230%. While it highlights the potential benefits of nitric oxide enhancement, it's important to note that this source is promotional material and may not provide a balanced view of the scientific evidence.