Consumption of Nitrate-Rich Beetroot Juice with or without Vitamin C Supplementation Increases the Excretion of Urinary Nitrate, Nitrite, and N-nitroso Compounds in Humans

Abstract

Consumption of nitrate-rich beetroot juice (BRJ) by athletes induces a number of beneficial physiological health effects, which are linked to the formation of nitric oxide (NO) from nitrate. However, following a secondary pathway, NO may also lead to the formation of N-nitroso compounds (NOCs), which are known to be carcinogenic in 39 animal species. The extent of the formation of NOCs is modulated by various other dietary factors, such as vitamin C. The present study investigates the endogenous formation of NOCs after BRJ intake and the impact of vitamin C on urinary NOC excretion. In a randomized, controlled trial, 29 healthy recreationally active volunteers ingested BRJ with or without additional vitamin C supplements for one week. A significant increase of urinary apparent total N-nitroso Compounds (ATNC) was found after one dose (5 to 47 nmol/mmol: p < 0.0001) and a further increase was found after seven consecutive doses of BRJ (104 nmol/mmol: p < 0.0001). Vitamin C supplementation inhibited ATNC increase after one dose (16 compared to 72 nmol/mmol, p < 0.01), but not after seven daily doses. This is the first study that shows that BRJ supplementation leads to an increase in formation of potentially carcinogenic NOCs. In order to protect athlete’s health, it is therefore important to be cautious with chronic use of BRJ to enhance sports performances.

Acceptability and Feasibility of a 13-Week Pilot Randomised Controlled Trial Testing the Effects of Incremental Doses of Beetroot Juice in Overweight and Obese Older Adults

“…This is consistent with results reported by Berends et al (2019) and Jajja et al (2015), who showed that urinary nitrate excretion remained at similar elevated levels during periods of the NO 3 − supplementation. The majority of ingested NO 3 − is excreted in urine during the following 24 h [47]. Previous studies have shown that urinary NO 3 − concentration returned to baseline 24 h after NO 3 − ingestion [48,49] which is consistent with our observation that urinary NO 3 − concentration decreased markedly when samples were collected 36 h after BJ ingestion in the low-dose NO 3 − group.…”

The benefits and risks of beetroot juice consumption: a systematic review

“…Vitamin C supplementation inhibited ATNC increase after one dose, but not after seven daily doses. This is the only study that investigated the effect of ingestion of high-nitrate levels through BRJ consumption on the formation of potentially carcinogenic NOCs, and its results demonstrated an increase in the excretion of these compounds after already one single dose (Berends et al 2019).…”

“…If these DNA lesions are not repaired, mutations can occur which are potentially involved in the process of cancer development (Vermeer & van Maanen, 2001). Consequently, ingestion of a high concentration of nitrate may increase the amount of endogenous NOCs being formed (Berends et al 2019). However, the current body of literature on the possible negative effects is rather limited as compared to the beneficial health effects of BRJ consumption.…”

Boosting nitric oxide in stress and respiratory infection: Potential relevance for asthma and COVID-19

“…Of particular concern is the finding that generation of N-nitroso compounds (NOCs), a potential carcinogen, can be stimulated by acute nitrate ingestion ( Zamani et al, 2020 ). One study has examined effects of beetroot juice on NOC excretion, and results indicate that acute consumption did result in increased levels of NOCs in urine ( Berends et al, 2019 ). However, more recent epidemiological studies have not found associations between nitrite and gastric cancer or esophageal cancer ( Ma et al, 2018 ).…”