질산염 대사 - 산화질소 탐구...

[문형철]

채소(시금치, 상추, 배추, 무, 양배추, 비트) 등에 많은 질산염

보충제로도 있음...

질산염 --> 아질산염 --> NO

타액(구강박테리아)가 질산염을 아질산염으로 전환

NO의 효능

1) 혈관이완, 확장 .. 혈압하강.. 뇌 혈류량 증대, 심장질환 예방

2) Cellular signal

3) type 1  muscle fiber(지근) - 근지구력 향상..

Nutrients. 2021 Sep; 13(9): 3183.

Published online 2021 Sep 13. doi: 10.3390/nu13093183

PMCID: PMC8465461

PMID: 34579061

Effects of Nitrate Supplementation on Exercise Performance in Humans: A Narrative Review

Matjaž Macuh1,* and Bojan Knap2,3

Gary D. Miller, Academic Editor

Author information Article notes Copyright and License information PMC Disclaimer

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Abstract

Nitrates have become increasingly popular for their potential role as an ergogenic aid. The purpose of this article was to review the current scientific evidence of nitrate supplementation on human performance. The current recommendation of nitrate supplementation is discussed, as well as possible health complications associated with nitrate intake for athletes, and dietary strategies of covering nitrate needs through sufficient intake of nitrate-rich foods alone are presented. Pubmed, Scopus, and Web of Science were searched for articles on the effects of nitrate supplementation in humans.

Nitrates are an effective ergogenic aid when taken acutely or chronically in the range of ~5–16.8 mmol (~300–1041 mg) 2–3 h before exercise and primarily in the case of exercise duration of ~10–17 min in less trained individuals (VO2max < 65 mL/kg/min). Nitrate needs are most likely meet by ingesting approximately 250–500 g of leafy and root vegetables per day; however, dietary supplements might represent a more convenient and accurate way of covering an athlete’s nitrate needs. Athletes should refrain from mouthwash usage when nitrate supplementation benefits are desired. Future research should focus on the potential beneficial effects of nitrate supplementation on brain function, possible negative impacts of chronic nitrate supplementation through different nitrate sources, and the effectiveness of nitrate supplementation on strength and high-intensity intermittent exercise.

질산염 Nitrates 은 

에르고제닉(활동성을 높이는) 보조제로서의 잠재적인 역할로 인해 

점점 더 인기를 얻고 있습니다. 

이 글의 목적은 

질산염 보충제가 

운동 능력에 미치는 현재의 과학적 증거를 검토하는 것입니다. 

현재 질산염 보충제에 대한 권장 사항과 

운동선수의 질산염 섭취와 관련된 건강상의 합병증에 대해 논의하고, 

질산염이 풍부한 식품의 충분한 섭취만으로 

질산염 필요량을 충족하는 식이 전략에 대해 소개합니다. 

인간에게 질산염 보충제가 미치는 영향에 관한 논문은 Pubmed, Scopus, Web of Science에서 검색했습니다. 

질산염 Nitrates 은 

운동 2~3시간 전에 5~16.8mmol(~300~1041mg) 범위에서 

급성 또는 지속적으로 섭취할 경우, 

주로 운동 시간이 10~17분인 경우(VO2max < 65mL/kg/min)에 효과적인 에르고제닉 보조제로서 

운동량이 적은 개인에게 도움이 될 수 있습니다. 

질산염 필요량은 

하루에 약 250~500g의 잎채소와 뿌리채소를 섭취하면

대부분 충족되지만,  -- 무우, 상추, 양배추, 비트..

식이 보충제를 섭취하는 것이 

운동선수의 질산염 필요량을 더 편리하고 정확하게 충족할 수 있는 방법일 수 있습니다. 

운동선수는 

질산염 보충제의 효과를 원할 때 

구강 청결제 사용을 자제해야 합니다. 

향후 연구에서는 

질산염 보충제가 

뇌 기능에 미치는 잠재적인 유익한 효과, 

다양한 질산염 공급원을 통한 만성 질산염 보충제의 부정적인 영향, 

근력 및 고강도 간헐적 운동에 대한 질산염 보충제의 효과에 초점을 맞추어야 합니다.

Keywords: nitrate, sports, performance, nitric oxide, dietary supplements, exercise science

1. Introduction

Nitric oxide (NO) is a signaling molecule involved in numerous vascular and cellular functions, such as cellular respiration, vasodilation, and angiogenesis. NO is produced through both endogenous and exogenous pathways by dietary nitrate (NO3−) ingestion. NO3− is an active compound found in certain NO3− rich vegetables and elicits potentially ergogenic as well as health-promoting effects. As such, NO3− presents as an interesting compound from both a sports perspective as an ergogenic aid as well as a potentially cost-effective tool for reducing the likelihood of cardiovascular events [1].

NO impacts exercise performance through several mechanisms: decreased fatigue during exercise, increased nutrient and oxygen delivery to the working muscles, and increased excretion of metabolic by-products of high-intensity exercise. There are several supplements promoted as so-called ‘NO boosters’. Historically, the amino acid L-arginine has been used extensively in these products to increase blood flow through NO production. Later, the non-essential amino-acid L-citrulline, found primarily in watermelons, cucumbers, and other melons, has replaced L-arginine in these supplements to a certain degree. Oral intake of L-citrulline as a dietary supplement increases the bioavailability of L-arginine to a greater extent than supplementation with L-arginine, as it is directly transported to the kidneys where it is converted to L-arginine, whereas L-arginine is subjected to catabolism via the enzyme arginase [2]. An extensive review of the literature on the effects of L-arginine and L-citrulline is beyond the scope of this article. However, it is worth noting that the positive effects of increased NO bioavailability may be induced through not only NO3− supplementation but potentially through L-arginine and L-citrulline supplementation as well.

NO3− supplementation and its effects on different types of exercise performance have gained attention in the past 2 decades. The purpose of this narrative review was to review the current scientific literature on the effects of NO3− supplementation on human performance, mechanisms by which NO3− may act as an ergogenic aid, and whether NO3− supplements are needed. The review was conducted using the online databases PubMed, Scopus, and Web of Science by searching keywords of ‘nitrate supplementation’ and ‘nitrate supplementation exercise performance’. Studies published up to September 2021 (English language restriction) were included. Studies completed in animal models or individuals with certain medical conditions were excluded from the review.

산화질소(NO)는 

세포 호흡, 

혈관 확장, 

혈관 신생 등 수많은 혈관 및 세포 기능에 관여하는 신호 분자입니다. 

 cellular respiration, vasodilation, and angiogenesis

NO는 

식이 질산염(NO3-) 섭취에 의한 

내인성 및 외인성 경로를 통해 생성됩니다. 

식이질산염(NO3-)는 

NO3-가 풍부한 특정 채소에서 발견되는 활성 화합물로, 

잠재적으로 에르고제닉 효과와 건강 증진 효과를 이끌어냅니다. 

따라서 

NO3-는 

심혈관 질환 발생 가능성을 낮추는 

잠재적인 비용 효율적인 도구일 뿐만 아니라 

운동 능력 향상 보조제로서 스포츠 측면에서 흥미로운 화합물입니다[1].

NO는 

운동 중 피로 감소, 

근육에 영양분 및 산소 공급 증가, 

고강도 운동의 대사 부산물 배설 증가 등 

여러 메커니즘을 통해 운동 능력에 영향을 미칩니다. 

소위 'NO 부스터 NO boosters '라고 홍보하는 

보충제가 몇 가지 있습니다. 

역사적으로 

아미노산 L-아르기닌은 

이러한 제품에서 NO 생성을 통해 

혈류를 증가시키기 위해 광범위하게 사용되어 왔습니다. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9921013/

최근에는 

수박, 오이, 기타 멜론에서 주로 발견되는 

비필수 아미노산인 L-시트룰린이 이러한 보충제에서 

L-아르기닌을 어느 정도 대체하고 있습니다. 

L-아르기닌은 

효소 아르기나제를 통해 이화 작용을 거치는 반면, 

L-시트룰린은 신장으로 직접 운반되어 

L-아르기닌으로 전환되기 때문에 

식이 보충제로 L-시트룰린을 경구 섭취하면 

L-아르기닌 보충제보다 생체 이용률이 더 높아집니다 [2]. 

L-아르기닌과 L-시트룰린의 효과에 대한 광범위한 문헌 검토는 

이 글의 범위를 벗어납니다. 

그러나

 NO 생체이용률 증가의 긍정적인 효과는 

NO3 보충제뿐만 아니라 

잠재적으로 L-아르기닌과 L-시트룰린 보충제를 통해서도 

유도될 수 있다는 점에 주목할 필요가 있습니다.

NO3 보충제와 

다양한 유형의 운동 수행 능력에 미치는 영향은 

지난 20년간 주목을 받아왔습니다. 

이 내러티브 리뷰의 목적은 

NO3- 보충제가 

운동 수행 능력에 미치는 영향, 

NO3-가 에르고제닉 보조제로 작용할 수 있는 메커니즘, 

NO3- 보충제의 필요 여부에 대한 최신 과학 문헌을 검토하는 것이었습니다. 

이 검토는 

온라인 데이터베이스인 PubMed, Scopus, Web of Science에서 

'질산염 보충제' 및 '질산염 보충제 운동 능력'이라는 

키워드를 검색하여 수행되었습니다. 

2021년 9월까지 발표된 연구(영어 제한)가 포함되었습니다. 동물 모델이나 특정 질병을 앓고 있는 사람을 대상으로 한 연구는 검토 대상에서 제외되었습니다.

1.1. Nitrates: Mechanisms of Action as an Ergogenic Aid

NO3− may improve sports performance primarily through its effects on skeletal muscle, blood vessels, and the brain [3]. Increased NO availability can affect mitochondrial respiration and biogenesis, increase blood flow in active muscles during physical activity, and consequently reduce adenosine triphosphate (ATP) consumption during muscle contraction, and reduce oxygen consumption during aerobic exercise [4]. The effect of NO3− on blood vessels is manifested through blood pressure reduction, an observation also seen in otherwise healthy populations with blood pressure values in reference ranges. NO3− may also increase heat loss through the skin during physical activity [3]. Research on the effect of NO3− on the brain is currently in its infancy and is not as well understood as are the effects on skeletal muscles and blood vessels. As such, there is currently no direct evidence that the addition of NO3− could, in fact, increase the availability of NO in the brain. Nevertheless, research completed in animal models reports that NO in the brain reduces oxygen consumption during exercise [5], accelerates heat loss through the skin during physical activity [6], and potentially exhibits protective effects against exercise-induced hyperthermia [6,7].

NO3-는 

주로 골격근, 혈관 및 뇌에 미치는 영향을 통해 

스포츠 수행 능력을 향상시킬 수 있습니다[3]. 

NO 가용성이 증가하면 

미토콘드리아 호흡과 

생체 생성에 영향을 미치고, 

신체 활동 중 활성 근육의 혈류를 증가시켜 

결과적으로 근육 수축 중 아데노신 삼인산(ATP) 소비를 줄이고, 

유산소 운동 중 산소 소비를 감소시킬 수 있습니다[4]. 

NO3-가 

혈관에 미치는 영향은 

혈압 감소를 통해 나타나며, 

이는 혈압 수치가 기준 범위 내에 있는 건강한 사람에서도 관찰됩니다. 

NO3-는 또한 

신체 활동 중 피부를 통한 열 손실을 증가시킬 수 있습니다 [3]. 

NO3-가 뇌에 미치는 영향에 대한 연구는 

현재 초기 단계에 있으며 

골격근과 혈관에 미치는 영향만큼 잘 알려져 있지 않습니다. 

따라서 

현재로서는 

NO3-의 첨가가 

실제로 뇌에서 NO의 가용성을 증가시킬 수 있다는 직접적인 증거는 없습니다. 

그럼에도 불구하고 동물 모델에서 수행된 연구에 따르면 

뇌의 NO는 운동 중 산소 소비를 줄이고[5], 

신체 활동 중 피부를 통한 열 손실을 가속화하며[6], 

잠재적으로 운동으로 인한 고열에 대한 보호 효과를 나타낸다고 합니다[6,7].

1.2. Nitrates: Metabolism

NO is synthesized either by ingesting foods rich in NO3−, L-arginine, L-citrulline, or through endogenous synthesis. NO synthesis from L-arginine takes place via its oxidation, catalyzed by the family of enzymes called nitric oxide synthase (NOS), and takes place in the presence of oxygen. The oxidation of L-arginine to NO was once thought to be the only way NO is formed in the body. However, we now know that this is not the case and that NO can be produced through the reduction of NO3− and nitrites (NO2−) in the body [8]. NO formation via the NO3−–NO2−–NO pathway takes place with a gradual decrease in oxygen concentration (hypoxia), which occurs during intense physical activity. This pathway can be described as an alternative or complementary pathway of NO formation in the absence of oxygen to the aforementioned pathway via the amino acid L-arginine [9].

After ingestion of NO3− from diet or dietary supplements, plasma NO3− levels peak after approximately 1–2 h or after 2–3 h for NO2− before concentrations of both compounds gradually decrease and return to baseline levels after approximately 24 h [10].

Digestion of ingested NO3− and NO2− begins in the mouth, where a certain portion (~25%) of ingested NO3− is digested by saliva via anaerobic bacteria that reside there and reduce NO3− to NO2−. The greater part of NO3− reduction takes place later in the stomach because of the low pH of the environment. Further reduction of NO2− takes place via a non-enzymatic reaction in the gastric lumen. Most of the circulating NO3− is eventually excreted through urine. However, approximately 20–25% of NO3− is taken up by the pancreas from the bloodstream and concentrated in saliva. The cycle of NO3− metabolism is thus completed and is then repeated, where the anaerobic bacteria in human saliva initially reduce NO3− to NO2−. NO2− and remaining non-reduced NO3− is then swallowed again where a smaller percentage of NO2− is further reduced to NO by the low pH environment of the gastric lumen [9]. Most of the remaining NO2−, however, re-enters the systemic circulation and is transported to specific locations throughout the body where they are reduced to NO via various enzymatic or non-enzymatic degradation pathways. The exact mechanism of NO2− re-entry into the circulation is unknown, but the reduction takes place primarily in the vascular system under conditions of hypoxia and reduced pH levels. Through the NO3−–NO2−–NO pathway of NO3− degradation, endogenously ingested nitrates are recycled by oral bacteria and act as a kind of reservoir of NO synthesis precursors [11].

It is important to note that this NO3− recycling process is severely impaired when oral mouthwashes are used on a regular basis as they destroy oral bacteria and consequently lower plasma NO3− levels [12,13]. This may be an important implication for athletes who should possibly be cautioned against mouthwash usage, especially during NO3− supplementation periods. Interestingly, chlorine-sterilized pool water does not seem to impair the NO3− reduction pathway through oral bacteria breakdown, as previously speculated by some. This has important implications for swimmers, a population where NO3− supplementation might be efficacious [14].

NO는 

NO3-, 

L-아르기닌, 

L-시트룰린이 풍부한 식품을 섭취하거나 

내인성 합성을 통해 합성됩니다. 

L-아르기닌으로부터의 NO 합성은 

산화질소 합성효소(NOS)라는 효소 계열에 의해 촉매되는 산화를 통해 이루어지며, 

산소가 있는 상태에서 이루어집니다. 

한때 

L-아르기닌이 NO로 산화되는 것이

 체내에서 NO가 형성되는 유일한 방법이라고 여겨졌습니다. 

그러나 이제는 이것이 사실이 아니며 

체내에서 NO3- 및 아질산염(NO2-)의 환원을 통해 

NO가 생성될 수 있다는 것을 알고 있습니다[8].

 NO3--NO2--NO 경로를 통한 NO 형성은 

격렬한 신체 활동 중에 발생하는 

산소 농도(저산소증)의 점진적인 감소와 함께 발생합니다. 

이 경로는 앞서 언급한 

아미노산 L-아르기닌을 통한 경로에 대한 산소가 없을 때 

NO 형성의 대체 또는 보완 경로로 설명할 수 있습니다[9].

식이 또는 식이 보충제를 통해 NO3-를 섭취한 후 

혈장 NO3- 수치는 약 1~2시간 후 또는 

NO2-의 경우 2~3시간 후에 최고조에 달한 후 

두 화합물의 농도가 점차 감소하고 

약 24시간 후에 기준 수준으로 돌아갑니다[10].

섭취한 NO3-와 NO2-의 소화는 

입안에서 시작되며, 

섭취한 NO3-의 일정 부분(~25%)은 

입안에 존재하는 혐기성 박테리아를 통해 

타액에 의해 소화되어 NO3-를 NO2-로 환원합니다. 

NO3- 감소의 대부분은 

환경의 낮은 pH로 인해 위장에서 더 늦게 일어납니다. 

NO2-의 추가 감소는 

위 내강에서 비효소 반응을 통해 이루어집니다. 

순환하는 NO3-의 대부분은 결국 소변을 통해 배설됩니다. 

그러나 

약 20-25%의 NO3-는 

혈류에서 췌장에 의해 흡수되어 

타액에 농축됩니다. 

이렇게 

NO3- 대사의 사이클이 완료된 후

 타액의 혐기성 박테리아가 

처음에 NO3-를 NO2-로 환원하는 과정이 반복됩니다. 

그런 다음 NO2-와 환원되지 않은 나머지 NO3-를 다시 삼키면 

위 내강의 낮은 pH 환경에 의해 

더 적은 비율의 NO2-가 NO로 추가로 환원됩니다 [9]. 

그러나 

남은 NO2-의 대부분은 

다시 전신 순환계로 유입되어 

다양한 효소적 또는 비효소적 분해 경로를 통해 

몸 전체의 특정 위치로 운반되어 NO로 환원됩니다. 

NO2가 순환계로 재진입하는 정확한 메커니즘은 알려져 있지 않지만, 

저산소증과 pH 수준이 감소된 조건에서 

주로 혈관계에서 감소가 일어납니다. 

NO3--NO2--NO- 분해 경로를 통해 

내인성적으로 섭취된 질산염은 

구강 박테리아에 의해 재활용되며 

일종의 NO 합성 전구체의 저장소 역할을 합니다[11].

구강 청결제를 

정기적으로 사용하면 

구강 박테리아를 파괴하여 

결과적으로 혈장 NO3- 수치를 낮추기 때문에 

이러한 NO3- 재활용 과정이 심각하게 손상된다는 점에 

유의하는 것이 중요합니다 [12,13]. 

이는 특히 NO3- 보충제를 복용하는 기간 동안 

구강청결제 사용에 주의를 기울여야 하는 운동선수에게 

중요한 시사점이 될 수 있습니다. 

흥미롭게도 

염소 소독된 수영장 물은 

이전에 일부에서 추측했던 것처럼 

구강 박테리아 분해를 통한 NO3- 감소 경로를 손상시키지 않는 것으로 보입니다. 

이는 NO3 보충제가 

효과적일 수 있는 집단인 수영 선수들에게 중요한 의미가 있습니다 [14].

2. Nitrates and Exercise Performance

NO3− have been frequently researched over the past decade and a half in terms of their impact on sports performance in a wide variety of training modalities. One of the first of such studies reported positive effects of NO3− supplementation on time to exhaustion [15]. Afterward, NO3− supplementation was found to have a positive impact on lowering oxygen consumption and time to exhaustion [16].

Several other studies report positive benefits of NO3− intake, such as lowering blood pressure [17,18], reduced use of ATP and reduced degradation of phosphocreatine (PCr), improved muscle contractile efficiency [16], reduced oxygen consumption during submaximal exercise [19,20,21], and improved performance [16,19,22,23,24]. Conversely, many other studies do not report the above-mentioned positive effects [25,26,27,28,29,30,31]. A more detailed analysis of studies examining the effects of NO3− supplementations on exercise performance is presented in Table 1.

NO3-는 

지난 10년 반 동안 다양한 훈련 방식에서 

스포츠 수행 능력에 미치는 영향에 대해 자주 연구되어 왔습니다. 

이러한 연구 중 첫 번째 연구 중 하나는 

NO3- 보충제가 탈진 시간에 긍정적인 영향을 미친다고 보고했습니다[15]. 

그 후 NO3 보충제는 

산소 소비량과 탈진 시간을 줄이는 데 

긍정적인 영향을 미치는 것으로 밝혀졌습니다 [16].

다른 여러 연구에서도 

혈압 강하[17,18], 

ATP 사용 감소 및 

포스포크레아틴(PCr) 분해 감소, 근육 수축 효율 개선[16], 

최대 이하 운동 시 산소 소비 감소[19,20,21], 

운동 능력 향상[16,19,22,23,24] 등 NO3 섭취의 긍정적인 이점을 보고한 바 있습니다. 

반대로 다른 많은 연구에서는 위에서 언급한 긍정적인 효과를 보고하지 않았습니다[25,26,27,28,29,30,31]. NO3 보충제가 운동 수행 능력에 미치는 영향을 조사한 연구에 대한 자세한 분석은 표 1에 나와 있습니다.

Table 1

Effects of nitrate supplementation on exercise performance.

Study (Year)Number of Participants (Sex)Participant CharacteristicsSupplementation ProtocolPerformance Protocol (Measured Variable)Main Findings

Larsen et al. (2007) [15]	9 (7 M, 2 F)	Cyclists and triathlon competitors (VO2peak 55 ± 3.7 mL/kg/min)	0.033 mmol NO3−/kg BM for 2 consecutive days thrice daily	Incremental ergometer test (time in s)	↔ Time to exhaustion
Bailey et al. (2009) [16]	8 (M)	Healthy and recreationally active VO2max 49 ± 5 mL/kg/min)	5.5 mmol NO3− for 6 consecutive days	High-intensity exercise (time in s)	↓ O2 uptake during high-intensity exercise ↑ Time to exhaustion ↓ Systolic blood pressure
Bailey et al. (2010) [17]	7 (M)	Healthy and recreationally active	5.1 mmol NO3− for 6 consecutive days	High-intensity exercise (time in s)	↓ Muscle phosphocreatine degradation ↑ Time to exhaustion ↑ ATP turnover
Vanhatalo et al. (2010) [18]	8 (5 M, 3 F)	Healthy individuals	5.2 mmol NO3− twice daily for 15 consecutive days	Incremental cycling test (power in W)	↓ Steady-state VO2 ↑ Peak power and work rate
Larsen et al. (2010) [32]	9 (7 M, 2 F)	Healthy and recreationally active (VO2max 3.72 ± 0.33 mL/kg/min)	0.1 mmol NO3−/kg BM for 2 consecutive days	Incremental ergometer test (time in s)	↔ Time to exhaustion
Vanhatalo et al. (2011) [33]	9 (7 M, 2 F)	Healthy and recreationally active	9.3 mmol NO3− split into three doses taken 24, 12, and 2.5 h prior to testing	Knee extension (time in s)	↑ Knee extension performance ↑ PCr recovery time constant
Lansley et al. (2011) [22]	9 (M)	Well-trained cyclists VO2peak 56 ± 5.7 mL/kg/min)	≃6.2 mmol NO3−	4 km and 16.1 km time trial (time in min and power in W)	↑ Power output in both 4 km and 16.1 km trial ↑ Performance in both 4 km and 16.1 km trial
Murphy et al. (2011) [23]	11 (5 M, 6 F)	Healthy and recreationally active	500 g beetroot (≃500 mg or 8 mmol NO3−)	5 km running time trial (velocity in km/h)	↔ Performance ↓ RPE
Masschelein et al. (2012) [19]	15 (M)	Healthy and recreationally active (VO2peak 61.7± 2.1 mL/kg/min)	0.07 mmol NO3−/kg BM/day for 6 consecutive days	Incremental ergometer test (time in s)	↓ VO2 and ↑ arterial O2 saturation during rest and exercise in hypoxic conditions
Bescos et al. (2012) [34]	13 (M)	Cyclists and triathlon competitors	11.8 mmol NO3−	Incremental test (time in s and power in W)	↔ Mean distance ↔ Power output
Peacock et al. (2012) [30]	10 (M)	Cross-country skiers (VO2max 69.6 ± 5.1 mL/kg/min)	1 g KNO3 (9.9 mmol or 614 mg NO3−)	5 km running time trial (time in s)	↔ Time trail performance ↔ O2 cost
Bond et al. (2012) [35]	14 (M)	Rowers	5 mmol NO3− for 6 consecutive days	6 × 500 m ergometer test at high-intensity (time in s)	↔ Rowing performance
Cermak et al. (2012) [36]	12 (M)	Cyclists and triathlon competitors (VO2peak = 58 ± 2 mL/kg/min; Wmax = 342 ± 10 W)	8 mmol NO3− for 6 consecutive days	10 km running time trial (time in s and power in W)	↑ Time trial performance ↑ Power output
Cermak et al. (2012) [25]	20 (M)	Cyclists and triathlon competitors (VO2peak 60 ± 1 mL/kg/min; Wmax 398 ± 7.7 W)	8.7 mmol NO3−	Cycling at 75 % Wmax to ≃1073 kJ (caloric-expenditure-based time trial) (time in min and power in W)	↔ Time trial ↔ Power output ↔ HR
Kelly et al. (2013) [37]	9 (M)	Healthy and recreationally active (VO2max 54.5 ± 7.5 mL/kg/min)	8.2 mmol NO3− for 5 consecutive days	Cyclic ergometry at 1) 60%, 2) 70%, 3) 80%, and 4) 100% Wmax (time in s)	↑ Exercise tolerance at 60%, 70%, and 80% peak power ↔ At 100% peak power
Breese et al. (2013) [38]	9 (4 M, 5 F)	Healthy individuals	8 mmol NO3− for 6 consecutive days	Incremental cycling test (time in s)	↑ VO2 kinetics ↑ Time-to-task failure
Wylie et al. (2013) [39]	10 (M)	Healthy individuals	(1) 4.2 or (2) 8.4 or (3) 16.8 mmol NO3−	Cycling to complete exhaustion (time in s)	↓ Steady-state O2 uptake during moderate-intensity exercise and ↑ time-to-task failure for 8.4 and 16.8 mmol NO3−
Wylie et al. (2013) [40]	14 (M)	Team sports athletes (VO2max 52 ± 7 mL/kg/min)	4.1 mmol NO3− twice daily for 2 consecutive days	Yo-Yo test (distance in m)	↑ Yo-Yo performance
Muggeridge et al. (2013) [20]	8 (M)	Kayak competitors (VO2max 49 ± 6.1 mL/kg/min)	5.0 mmol NO3−	15 min rowing at 60 % Wmax (power in W)	↓ VO2 ↔ Peak power or time trial performance
Christensen et al. (2013) [26]	10 (M)	Cyclists (VO2max 72 ± 4 mL/kg/min)	5.0 mmol NO3− 4 for 6 consecutive days	Repeated sprints (power in W) and time trial ≃1677 kJ (energy-expenditure-based time trial) (time in s and power in W)	↔ Vo2 kinetics ↔ Exercise economy ↔ Time trial performance
Hoon et al. (2014) [41]	28 (M)	Cyclists	4.1 mmol NO3−	4 min time trial (power in W)	↔ Time trial performance
Boorsma et al. (2014) [42]	8 (M)	Elite 1500 m runners (VO2max 80 ± 5 mL/kg/min)	19.5 mmol NO3−	1500 m running time trial (time in s)	↔ VO2peak ↔ Time trial performance
Martin et al. (2014) [43]	16 (9 M, 7 F)	Team sports athletes (VO2max M: 57.4 ± 8 mL/kg/min; F: 47.2 ± 8 mL/kg/min)	4.83 mmol NO3−	8 s repeated sprints test on cyclic ergometer (number of sprints, work in kJ, power in W)	↔ Mean power output ↓ Number of sprints ↓ Total work
Peeling et al. (2015) [44]	6 (M)	National-level kayak competitors (VO2peak 57.15 ± 2.8 mL/kg/min)	5.5 mmol NO3−	4 min maximal ergometer test (power in W and distance in m)	↓ VO2 ↑ Exercise economy ↑ Time trial performance
Porcelli et al. (2015) [21]	21 (M)	8 individuals with lower aerobic capacity (VO2peak 28.2–44.1 mL/kg/min), 7 individuals with medium aerobic capacity (VO2peak: 45.5–57.1 mL/kg/min), and 6 individuals with high aerobic capacity (VO2peak: 63.9–81.7 mL/kg/min)	5.5 mmol NO3− for 5 consecutive days	3 km running time trial	↑ Time trial performance for lower and medium aerobic capacity ↔ Time trial performance for high aerobic capacity
Wylie et al. (2015) [45]	10 (M)	Healthy and recreationally active	8.2 mmol NO3− 3, 4 or 5 consecutive days	24 × 6 s sprints with 24 s rest; 7 × 30 s sprints with 240 s rest; 6 × 60 s sprints with 60 s rest (power in W)	↑ Power output for condition 1 ↔ Power output for conditions 2 and 3
McQuillan et al. (2017a) [27]	9 (M)	Cyclists (VO2peak: 68 ± 3 mL/kg/min)	9 mmol NO3− 3 for 7 consecutive days	1 km time trial at fourth and seventh day of investigation and 4 km time trial at third in sixth day of investigation (time in s and power in W)	↔ Time trial ↔ Power output
McQuillan et al. (2017b) [28]	8 (M)	Cyclists (VO2peak = 63 ± 4 mL/kg/min)	~4 mmol NO3− for 8 consecutive days	4 km time trial (time in s in power in W)	↔ Time trial ↔ Power output
Christensen et al. (2017) [46]	17 (M)	8 recreationally active (VO2max 46 ± 3 mL/kg/min) and 9 well-trained cyclists (VO2max: 64 ± 3 mL/kg/min)	9 mmol NO3−	Incremental test for cycling and arm cranking (power in W)	↔VO2max ↑ Peak power for cycling ↔ Peak power for arm cranking
Nyakayiru et al. (2017a) [29]	17 (M)	Cyclists and triathlon competitors (65 ± 4 mL/kg/min, Wmax 411 ± 35 W)	4 mmol NO3− for 6 consecutive days	10 km time trial (time in s)	↔VO2 ↔ Time trial
Nyakayiru et al. (2017b) [24]	32 (M)	Football players	12.9 mmol NO3− for 6 consecutive days	Yo-Yo test (distance in m)	↑ Covered distance
Vasconcellos et al. (2017) [47]	25 (14 M, 11 F)	Runners (M: VO2peak 64.31 ± 4.71 mL/kg/min−1; F: VO2peak 52.79 ± 4.57 mL/kg/min	9.92 NO3− ± 1,97 mmol	High-intensity running (time in s)	↔ Time to fatigue ↔ VO2max ↓ Blood glucose ↔ Systolic and diastolic blood pressures ↔ Serum cortisol, ↔ Blood lactate
Shannon et al. (2017) [48]	8 (M)	Runners in triathlon competitors (VO2max: 62.3 ± 8.1 mL/kg/min)	~12.5 mmol NO3−	Running for 1500 m and 10 000 m (time in s)	↔ Resting blood pressure ↑ Blood lactate for 1500 m time trial ↔ Blood lactate for 10,000 m time trial ↑ Time trial performance for 1500 m ↔ Time trial performance for 10,000 m
De Castro et al. (2018) [49]	14 (M)	Healthy and recreationally active runners (VO2max: 45.4 ± 5.9 mL/kg/min)	8.4 mmol NO3− for 3 consecutive days	10 km running time trial (time in min and velocity in km/h)	↔ Time trial performance ↔ Mean velocity
Cuenca et al. (2018) [50]	15 (M)	Healthy and recreationally active	6.4 mmol NO3−	WAnT and CMJ (power in W, time to Wpeak)	↑ Peak and mean power output ↓ Time taken to reach Wpeak
Oskarsson et al. (2018) [51]	9 (M 7, F 2)	(M: VO2max 59.0 ± 2.9 mL/kg/min; F: VO2max 53.1 ± 11.4 mL/kg/min)	6.4 mmol NO3	1 km running time trial (time in s)	↔ Relative oxygen uptake, running economy, respiratory exchange ratio, HR, or RPE at submaximal intensities ↔ Performance, maximum HR, peak blood lactate concentration, or RPE during the maximal-intensity time trial
Jo et al. (2019) [52]	29 (M 15, F 14)	Healthy and recreationally active	8 mmol NO3− for 15 consecutive days	8 km time trial (time in s, power in W, velocity in km/h)	Multiday NO3− supplementation: ↑ Time trial performance ↑ Average power ↑ Velocity Single serving NO3−: ↔ Time trial performance ↔Average power ↔ Velocity
Rokkedal-Lausch et al. (2019) [53]	12 (M)	Cyclists (VO2max 66.4 ± 5.3 mL/min/kg)	12.4 mmol NO3− for 7 consecutive days	10 km time trial in normoxic and hypoxic conditions (time in s and power in W)	↑ Time trial performance in normoxic and hypoxic conditions ↔ HR ↔ Oxygen saturation ↔ Muscle oxygenation
Esen et al. (2019) [54]	10 (5 M, 5 F)	Swimmers with a minimum of 10 years training experience and minimum of 5 years competing experience	~800 mg NO3− for 3 consecutive days	100 in 200 m swimming for time (time in s)	↔ Time trial performance for 100 and 200 m ↓ Systolic blood pressure
Wickham et al. (2019) [55]	12 (F)	Healthy and recreationally active (VO2peak: 40.7 ± 4.3 mL/kg/min)	Acute and chronic supplementation (~26 mmol) of NO3− for either 1 or 8 consecutive days	10 min time trial at 50 and 70 % VO2max (time in s)	↔ MVC voluntary activation ↔ Peak twitch torque, ↔ time to peak torque, ↔ half relaxation time ↔ Time trial performance ↔ VO2
Kent et al. (2019) [56]	12 (M)	Team sports athletes (VO2peak 53.1 ± 8.7 mL/kg/min)	12.9 mmol NO3−	Four cycling sprints at sea and 3000 m altitude	↔ Peak and mean power
Mosher et al. (2019) [57]	11 (M)	Cyclists (VO2max: 60.8 ± 7.4 mL/kg/min)	12.8 mmol NO3− for 3 consecutive days	40 km time trial (time in s)	↔ Time trial performance ↔ VO2 ↔ Blood lactate ↔ RPE
Ranchal-Sanchez et al. (2020) [58]	12 (M)	Healthy and recreationally active	6.4 mmol NO3−	Incremental test at 60, 70, and 80% maximal power for bench press and squat (number of repetitions, power in W, and velocity in m/s)	↑ NOR for 60 and 70% 1 RM ↔ NOR for 80% 1 RM ↑ NOR for squat ↔ NOR for bench press ↔ Power ↔ Velocity
López-Samanes et al. (2020) [59]	13 (M)	Professional tennis players	300 mg NO3−	Serving speed, CMJ, IHS, 5-0-5 agility test, and 10 m sprints test	↔ Serve velocity ↔ CMJ ↔ IHS ↔ 5-0-5 agility test ↔ Sprint performance
Liubertas et al. (2020) [60]	13 (M)	Healthy individuals	Acute and chronic intake (for 6 consecutive days) of 400 mg NO3−	Incremental cycling test first, third, and sixth day of investigation (power in W and VO2max)	↑ Peak power ↑ VO2max
Rodríguez-Fernández et al. (2020) [61]	18 (M)	Healthy and recreationally active	800 mg NO3−	Four sets of eight all-out half-squats with each set completed at different moment intertia (power in W)	↑ Mean and peak power output in the concentric and eccentric movement phases
Jonvik et al. (2021) [62]	15 (M)	Recreationally active	985 mg NO3− for 6 consecutive days	CMJ, upper leg voluntary isometric (30° and 60° angle) and isokinetic contractions (60, 120, 180, and 300°s−1) and test of 30 reciprocal isokinetic voluntary contractions at 180°s−1	↔ CMJ ↔ Maximal isometric knee extensor strength and isokinetic knee extension power ↔ Muscular endurance
Dumar et al. (2021) [63]	10 (M)	National Collegiate Athletic Association sprinters	400 mg NO3− 2 h prior to exercise	3 × 15 s WAnT with 2 min rest in the AM and PM (power in W and anaerobic capacity in Wkg−1)	NO3− attenuated the decrease in AM exercise performance ↔ RPE ↓ HR
Marshall et al. (2021) [64]	22 (12 M, 10 W)	Healthy adults	~12.5 mmol NO3− for 20 consecutive days	Harvard Step Test fitness at baseline (44 m altitude), 2350 m (day 9), 3400 m (day 12), and 4800 m (day 17)	NO3− attenuated the decline in fitness scores with altitude ↑ HR recovery ↔ RPE ↔ High-altitude illness occurrence
Fowler et al. (2021) [65]	11 (M)	Healthy adults (VO2max: 41.1 ± 3.6 mL/kg/min)	∼9.2 mmol NO3− for 5 consecutive days	Cycling exercise tolerance test in hot and dry conditions (35 °C, 28% relative humidity)	↔ Performance ↓ Arterial pressure ↔ Sweat rate ↔ Heart rate ↔ Oxygen consumption and carbon dioxide production ↔ Thermal sensation
Townsend et al. (2021) [66]	16 (M)	Division I baseball athletes	180 mg NO3− daily for 11 weeks	1 RM bench press, WAnT, body composition analysis via a 4-compartment model	↔Perfromance (1 RM bench press and WAnT; observed trend for improved peak power in the WAnT) ↔ Body composition and muscle thickness ↔ HR and blood pressure

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↑ = Significantly greater (p < 0.05) compared with placebo; ↔ = no significant change compared with placebo; ↓ = significantly lower (p < 0.05) compared with placebo; NO3− = nitrates; BM = body mass; PCr = phosphocreatine; RPE = rating of perceived exertion; WAnT = Wingate anaerobic test; CMJ = counter movement jump; HR = heart rate; MVC = maximum voluntary strength; NOR = number of repetitions; 1 RM = repetition maximum; HIS = isometric grip strength. Potential reasons why some studies presented in Table 1 report a positive effect of NO3− supplementation and others do not may result from different research methodological approaches, different testing, and supplementation protocols, potentially through the production of free radicals through NO reaction with O2, and differences between participants training status.

The latter may be the most prominent reason why researchers report different findings, and many factors may contribute to this effect. The first is that intense exercise itself increases NOS activity [67], making top-tier athletes less dependent on the NO3−–NO2−–NO pathway of NO production and having higher baseline levels of NO3− in comparison to less trained individuals [4]. Poveda et al. (1997) reported a 158% increase in baseline plasma NO2− concentration in a sample of 10 well-trained runners and cyclists versus non-trained individuals [68]. Porcelli et al. (2015) reported that when VO2max is low (<65 mL/kg/min), the effect of NO3− on reducing oxygen consumption during exercise is most pronounced and can be as high as 10%. On the other hand, at higher VO2max (>65 mL/kg/min), the effect of NO3− is negligible [21]. It is worth noting that VO2max is affected by both sports’ specificity as well as age. Certain elite-level athletes where NO3− supplementation might be useful participating in sports requiring not only endurance, but also speed, strength, and anaerobic capacity might not have the same level of VO2max as solely endurance athletes [69,70]. Additionally, in master athletes, there is a progressive decline of VO2max with age [71]. Thus, a specific cut-off point at 65 mL/kg/min justifying the usage of NO3− supplementation might or not might not be valid in all sports situations.

The observation that NO3− supplementation effects are less pronounced in better-trained individuals is also supported in a systematic review and meta-analysis by Campos et al. (2018) [3]. These researchers reported that despite the smaller impact of NO3− on the performance of well-trained individuals, the effect of NO3− should not be neglected. NO3− is currently regarded as one of a handful of dietary supplements with a direct, positive effect on athlete’s performance based on the latest consensus statement by the International Olympic Committee (IOC) [72]. The effect of NO3− supplementation on performance may be particularly desirable on competition day, where the differences between the competitors are marginal.

Additionally, diet may also influence NO3− supplementation effects in well-trained individuals. This effect, speculative in nature, relates to the general eating habits of elite athletes. We can assume that most top athletes include decent amounts of foods rich in NO3− as well as L-arginine and L-citrulline, making the effect of the dietary supplementation less pronounced [4]. Of course, the latter works solely on the assumption that the athlete consumes enough NO3−-rich foods, and if the intake of NO3− from the diet is too low, dietary supplement usage will most likely yield greater benefits. A parallel may be drawn with creatine supplementation. Vegetarians and vegans who consume diets poorest in creatine (meat, fish, and eggs) have the lowest levels of muscle creatine phosphate, and the effect of creatine supplementation on performance is significantly more pronounced in this population versus omnivores [73].

Lastly, a difference in performance outcomes observed in studies using NO supplementation might be attributed to NO’s ability to interact with other free radicals. As NO half-life in vivo is in the order of a few seconds, this reaction might be dependent on its initial concentration [74], thus making it potentially problematic in the context of NO supplementation where a bolus of NO3− is ingested at once without the presence of other ingredients affecting its digestion. In this context, a major concern might be the interaction between NO and superoxide (O2) leading to peroxynitrite (OONO−) formation—a highly reactive nitrogen species (RNS) affecting mitochondrial function, signal transduction, and stress response [75,76]. Chronic OONO− formation might directly lead to the production of RNS and reactive oxygen species (ROS) in other subcellular compartments, leading to increased oxidative stress [77], which might affect performance. As with other supplements affecting oxidative stress, special emphasis on using such supplements in the right context might have to be taken when using NO3− supplementation. For example, high doses of vitamin C and E have been shown to blunt aerobic exercise adaptations [78,79]. High antioxidant usage has also been shown to blunt body composition improvements following a resistance training protocol [80]. This might limit the usage of such supplements during specific conditions where an athlete’s recovery is more important than optimal adaptation (e.g., tournaments where an athlete has many competitions in a short time frame). For NO3− supplementation, no such guidelines can be given, and to our knowledge, no research has looked directly into differences in RNS formation from NO3− supplementation or via NO3− rich diet but should be taken into account, especially when chronic NO3− supplementation is being considered.

There are also several literature reviews and meta-analyses examining the effectiveness of NO3− supplementation on exercise performance. Hoon et al. (2013) reported a statistically significant improvement in performance for constant power/speed tests and smaller, statistically insignificant but positive effects in the case of incremental tests and time trials [81]. However, the meta-analysis did not consider differences in NO3− supplementation protocols between trials as well as the training status of individuals. Pawlak-Chaouch et al. published a meta-analysis including 26 randomized and placebo-controlled studies in 2016 and reported a significant reduction in VO2 during submaximal exercise [82]. Afterward, a meta-analysis by Van De Wall and Vukovich in 2018 reported that NO3− supplementation can improve tolerance to and efficiency of continuous high-intensity exercise and maximal exercise with increasing intensity [4]. The authors recommend the effectiveness of both acute as well as chronic NO3− supplementation (up to 15 days) when taken in an amount of 5–9 mmol with similar conclusions being found in a meta-analysis by McMahon et al. (2016) on the impact of NO3− supplementation specifically on endurance performance [83]. This meta-analysis included 47 studies and reported that the effect of NO3− supplementation was efficient on submaximal aerobic capacity, but lower effectiveness for time trial tests, which is in line with past research by Hoon et al. (2013) [81].

후자가 연구자들이 서로 다른 결과를 보고하는 가장 두드러진 이유일 수 있으며, 여러 가지 요인이 이러한 효과에 기여할 수 있습니다. 

첫 번째는 

격렬한 운동 자체가 

NOS 활동을 증가시켜[67], 

최고 수준의 운동선수는 훈련이 덜 된 사람에 비해 

NO3--NO2--NO 생성 경로에 덜 의존하고 

기준치 NO3- 수치가 더 높다는 것입니다[4]. 

(1997)은 잘 훈련된 10명의 달리기 선수와 

사이클리스트 샘플에서 

훈련되지 않은 개인에 비해 기준 혈장 NO2- 농도가 

158% 증가했다고 보고했습니다 [68]. 

Porcelli 등(2015)은 

VO2max가 낮을 때(<65mL/kg/min) 운

동 중 산소 소비를 감소시키는 NO3-의 효과가 가장 두드러지며 10%까지 높아질 수 있다고 보고했습니다. 

반면, 

VO2max가 높을수록(>65mL/kg/min) 

NO3-의 효과는 무시할 수 있습니다[21]. 

VO2max는 

나이뿐만 아니라 스포츠의 특이성에도 영향을 받는다는 점에 

주목할 필요가 있습니다. 

지구력뿐만 아니라 

속도, 근력, 무산소 능력을 필요로 하는 스포츠에 참여하여 

NO3- 보충제가 유용할 수 있는 특정 엘리트 수준의 운동선수는 

지구력 운동선수와 같은 수준의 VO2max를 갖지 못할 수 있습니다[69,70]. 

또한, 

숙련된 운동선수의 경우 나이가 들면서 

VO2max가 점진적으로 감소합니다[71]. 

따라서 

NO3 보충제 사용을 정당화하는 65mL/kg/min의 특정 컷오프 지점은 모든 스포츠 상황에서 유효할 수도 있고 그렇지 않을 수도 있습니다.



NO3 보충제의 효과가 잘 훈련된 사람에게서 덜 두드러진다는 관찰은 

Campos 등(2018)의 체계적인 검토 및 메타 분석에서도 뒷받침됩니다[3]. 

이 연구자들은 NO3-가 잘 훈련된 개인의 운동 능력에 미치는 영향은 작지만, NO3-의 효과를 무시해서는 안 된다고 보고했습니다. NO3-는 현재 국제 올림픽 위원회(IOC)의 최신 합의문에 따라 선수의 운동 능력에 직접적이고 긍정적인 영향을 미치는 소수의 식이 보충제 중 하나로 간주되고 있습니다[72]. NO3 보충제가 경기력에 미치는 영향은 선수들 간의 차이가 미미한 경기 당일에 특히 바람직할 수 있습니다.

또한, 식단도 

잘 훈련된 개인의 NO3 보충제 효과에 영향을 미칠 수 있습니다. 

이러한 효과는 추측에 불과하지만 

엘리트 운동선수의 일반적인 식습관과 관련이 있습니다. 

대부분의 최고 운동선수들은 

L-아르기닌과 L-시트룰린뿐만 아니라 

NO3-가 풍부한 식품을 적절히 섭취하기 때문에 

식이 보충제의 효과가 덜 두드러진다고 가정할 수 있습니다 [4]. 

물론 후자는 

운동선수가 NO3가 풍부한 음식을 충분히 섭취한다는 전제하에 작동하며, 

식단에서 NO3 섭취량이 너무 적으면 

식이 보충제를 사용하면 더 큰 효과를 얻을 가능성이 높습니다. 

크레아틴 보충제를 섭취하는 것도 마찬가지입니다. 

크레아틴이 가장 부족한 식단(육류, 생선, 계란)을 섭취하는 채식주의자와 비건은 

근육 크레아틴 인산염 수치가 가장 낮으며, 

크레아틴 보충제가 운동 능력에 미치는 영향은 

이 집단에서 잡식주의자에 비해 훨씬 더 뚜렷하게 나타납니다[73].

마지막으로, 

NO 보충제를 사용한 연구에서 관찰된 운동 능력 결과의 차이는 

NO가 다른 자유 라디칼과 상호 작용하는 능력에 기인할 수 있습니다. 

생체 내 NO 반감기는 

수 초 정도이므로 

이 반응은 초기 농도에 따라 달라질 수 있으므로[74], 

소화에 영향을 미치는 다른 성분 없이 한 번에 많은 양의 NO3-를 섭취하는 

NO 보충제의 맥락에서 잠재적으로 문제가 될 수 있습니다. 

이러한 맥락에서 주요 관심사는 

미토콘드리아 기능, 

신호 전달 및 스트레스 반응에 영향을 미치는 반응성이 높은 질소 종(RNS)인 

과산화질소(O2)와 NO의 상호작용으로 인한 

과산화아질산염(OONO-) 형성일 수 있습니다[75,76]. 

만성적인 OONO- 형성은 

다른 세포 내 구획에서 RNS 및 활성 산소종(ROS)의 생성으로 직접 이어져 

산화 스트레스를 증가시켜[77] 

운동 능력에 영향을 미칠 수 있습니다. 

산화 스트레스에 영향을 미치는 다른 보충제와 마찬가지로 

NO3 보충제를 사용할 때는

 올바른 맥락에서 이러한 보충제를 사용하는 데 특별히 주의를 기울여야 할 수 있습니다. 

예를 들어, 고용량의 비타민 C와 E는 

유산소 운동 적응을 둔화시키는 것으로 나타났습니다 [78,79]. 

또한 항산화제를 많이 섭취하면 

저항 운동 프로토콜에 따른 체성분 개선 효과가 둔화되는 것으로 나타났습니다 [80].

 따라서 최적의 적응보다 선수의 회복이 더 중요한 특정 조건(예: 단기간에 많은 경기를 치르는 토너먼트)에서는 이러한 보충제의 사용이 제한될 수 있습니다. NO3 보충제의 경우 이러한 가이드라인을 제시할 수 없으며, 저희가 아는 한 NO3 보충제 또는 NO3가 풍부한 식단을 통한 RNS 형성의 차이를 직접적으로 조사한 연구는 없지만, 특히 만성적인 NO3 보충제를 고려하는 경우 이를 고려해야 합니다.

또한 NO3 보충제가 운동 수행 능력에 미치는 영향을 조사한 여러 문헌 검토와 메타 분석도 있습니다. 훈 등(2013)은 일정한 파워/속도 테스트의 경우 통계적으로 유의미한 성능 향상을, 점진적 테스트와 타임 트라이얼의 경우 통계적으로 미미하지만 긍정적인 효과가 있다고 보고했습니다[81]. 그러나 메타 분석에서는 시험 간 NO3 보충 프로토콜의 차이와 개인의 훈련 상태는 고려하지 않았습니다. 2016년에 26개의 무작위 및 위약 대조 연구를 포함한 메타분석을 발표한 Pawlak-Chaouch 등은 최대치 이하 운동 중 VO2가 유의미하게 감소한다고 보고했습니다[82]. 그 후 2018년 Van De Wall과 Vukovich의 메타 분석에 따르면 NO3 보충제는 지속적인 고강도 운동과 강도가 증가하는 최대 운동에 대한 내성과 효율성을 개선할 수 있다고 보고했습니다[4]. 저자들은 NO3 보충제가 특히 지구력 수행 능력에 미치는 영향에 대한 McMahon 등(2016)의 메타 분석에서도 비슷한 결론을 얻었으며, 5-9mmol의 양을 섭취할 경우 급성 및 만성 NO3 보충제(최대 15일)의 효과를 모두 권장합니다 [83]. 이 메타 분석에는 47개의 연구가 포함되었으며, NO3 보충제의 효과는 최대 유산소 능력에는 효과적이지만 타임 트라이얼 테스트에는 효과가 낮다고 보고했는데, 이는 Hoon 등(2013)의 과거 연구와 일치하는 결과입니다[81].

2.1. Nitrates: Supplementation Protocol

Even though a linear correlation exists between the amount of NO3− ingested and the increase in plasma NO3− levels, we can assume that there is an upper limit of NO3− intake that still elicits a positive effect on performance. Wylie et al. (2013) reported that ingestion of 4.2 mmol NO3− did not affect VO2 during moderate-intensity cycling, but VO2 was affected by NO3− supplemented at 8.4 mmol and 16.8 mmol [39]. However, ingestion of 16.8 mmol NO3− compared to 8.4 mmol NO3− did not provide additional benefits. Thus, we can assume that the effect of NO3− on performance exists within a specific interval. This interval is most likely between 5–9 mmol (310–560 mg) NO3− taken either acutely 2–3 h before exercise [41] or chronically over an extended period [4]. Similar recommendations can also be found from the IOC [72] and Senefeld et al. (2020) [84]. The authors of the latter meta-analysis report that the effect of NO3− is not statistically significant if NO3− is taken less than 2 h before exercise as this does not allow enough time for NO3− to NO conversion.

The effect of acute or chronic NO3− intake is expected to be similar based on the current literature [84]; however, chronic NO3− intake of more than 3 consecutive days before the race may potentially reap greater benefits for well-trained athletes [85].

NO3- 섭취량과 혈장 NO3- 수치 증가 사이에는 

선형적인 상관관계가 존재하지만, 

운동 능력에 긍정적인 영향을 미치는 NO3- 섭취의 상한선이 있다고 가정할 수 있습니다. 

Wylie 등(2013)은 중간 강도의 사이클링을 하는 동안

 4.2mmol NO3- 섭취는 

VO2에 영향을 미치지 않았지만, 

8.4mmol과 16.8mmol로 보충한 NO3-는 VO2에 영향을 미쳤다고 보고했습니다[39]. 

그러나 8.4mmol NO3-에 비해 16.8mmol NO3-의 섭취는 추가적인 이점을 제공하지 않았습니다. 따라서 NO3-가 성능에 미치는 영향은 특정 간격 내에 존재한다고 가정할 수 있습니다. 이 간격은 운동 2~3시간 전에 급성으로 섭취하거나[41] 장기간에 걸쳐 만성적으로 섭취하는 5-9mmol(310-560mg) NO3-일 가능성이 가장 높습니다[4]. 유사한 권장 사항은 IOC [72] 및 Senefeld 외(2020) [84]에서도 찾아볼 수 있습니다. 후자의 메타 분석의 저자들은 운동 2시간 이내에 NO3-를 섭취하면 NO3-가 NO로 전환될 시간이 충분하지 않기 때문에 NO3-의 효과가 통계적으로 유의미하지 않다고 보고합니다.

현재 문헌에 따르면 급성 또는 만성 NO3- 섭취의 효과는 비슷할 것으로 예상되지만[84], 잘 훈련된 운동선수에게는 경기 전 3일 이상 연속으로 만성 NO3-를 섭취하는 것이 더 큰 이점을 얻을 수 있습니다[85].

2.2. Nitrates: Effects of Exercise Type and Conditions

The IOC reports the effectiveness of NO3− differs across not only training status but exercise type and trial duration as well [72]. As such, the impact of NO3− supplementation is reported to be in the range of 4–25% for time to exhaustion tests and 1–3 % for sport-specific tests lasting less than 40 min. NO3− is expected to have the greatest effect between the range of approximately 12 and 40 min. Furthermore, within this time frame, the effects of NO3− supplementation are likely most pronounced for exercise lasting between 601 and 999 s (~10–17 min), with the effects of NO3− being effective regardless of normoxic or hypoxic conditions [84].

Effects of NO3− supplementation have been studied in a wide variety of performance tests. However, the effects are most likely especially pronounced in time to exhaustion tests rather than time trial tests or incremental power tests. This may be due to the fact that time to exhaustion tests are supposedly better at measuring an athlete’s endurance capacity and are highly influenced by psychological factors (e.g., motivation, boredom, etc.) [3,86]. As for the type of exercise, Senefeld et al. (2020) report a significant effect of NO3− on cycling and running, the most commonly studied training modalities in research on NO3− supplementation, but not in knee extension tests or rowing rests. However, the lack of effect is most likely due to the relatively low proportion of studies completed on these two forms of performance tests rather than the exercise type per se [84].

NO3− might be particularly effective for team sports athletes because of their potential beneficial effect on cognition. Athletes who participate in team sports are forced to make many quick decisions during training and competition. However, prolonged high-intensity exercise can have a negative impact on reaction time and task performance [87]. Thompson et al. (2015) reported a statistically significantly shorter reaction time in individuals receiving NO3− supplementation in the amount of 6.4 mmol to 12.8 mmol for 7 consecutive days [88]. These positive effects of NO3− supplementation on cognition may arise from the positive effect of NO on neurovascular coupling [89] and increased cerebral perfusion, primarily in the prefrontal cortex responsible for executive function [90]. NO3− thus has a potentially positive effect on reducing the decline in cognitive function, primarily athlete’s reaction time, which is otherwise associated with repetitive high-intensity intermittent exercise.

A large majority of studies on NO3− supplementation effects on performance have been completed on endurance tests. Some research, however, focuses on investigating these effects on high-intensity exercise and strength, where mixed results are observed. Thompson et al. (2016) reported improvements in sprints in the Yo-Yo test after NO3− supplementation [91]. A similar effect in the same test in a sample of 32 football players is also reported by Nyakayiru et al. (2017) [24]. Cuenca et al. (2018) also reported an ergogenic effect of acute NO3− intake of 6.4 mmol in the Wingate test, primarily in the first half of the sprints [50]. However, Martin et al. (2014) do not report a positive effect of NO3− on the protocol of 8 s sprints with 30 s pauses [43].

A systematic review by San Juan et al. (2020) on the effect of NO3− on weight training in an otherwise limited sample of four studies reported a positive effect of NO3− on upper body strength and the number of repetitions performed in upper body strength test (bench press) as well as lower body strength test (squat) [92]. We certainly need more research into the impact of NO3− on high-intensity exercise and strength, but preliminary results suggest that NO3− could be beneficial in this sport context as well.

Another avenue of NO3− effects on performance is research completed in extreme conditions, such as hypoxic and cold environmental settings (e.g., mountaineering, skiing, altitude training, etc.). As altitude increases, hypoxic conditions reduce O2 availability and decrease exercise performance. We can somewhat overcome this problem with altitude acclimatization; however, this process may take up to several weeks to fully manifest, which is not always possible in certain sports situations. Additionally, physical fitness otherwise seen at sea level might not ever be fully regained, even with prolonged acclimatization [93]. It is suggested that NO plays an essential role in hypoxia-induced vasodilatation, thereby ensuring adequate O2 availability to the working muscle and brain tissue during hypoxic conditions [94,95]. Certain populations native to higher altitudes (e.g., Sherpa) have been proposed to exert abnormal hypoxic tolerance in part due to elevated circulating levels of NO [96]. Indeed, research completed at simulated altitude shows the benefits of NO3− supplementation on certain physiological parameters (e.g., improved mitochondrial respiration, O2 consumption during exercise, etc.). However, these findings do not seem to be observed in field tests at ’real’ altitudes, making real-world applications limited [93,96,97]. Certain researchers have postulated that chronic NO3− supplementation might even be detrimental for athletes training at altitude from a perspective of possibly blunting hypoxic adaptations by decreasing arterial and muscle O2 saturation, which may act as a signal for such adaptations [98]. As such, there is currently no clear benefit of NO3- supplementation for athletes performing at high altitudes, and more research is needed on this specific topic.

IOC는 

NO3-의 효과가 훈련 상태뿐만 아니라 

운동 유형과 시험 기간에 따라 다르다고 보고합니다[72]. 

따라서 

NO3- 보충제의 효과는 

탈진 시간 테스트의 경우 4-25%, 40분 미만 지속되는 스포츠별 테스트의 경우 

1-3% 범위인 것으로 보고되었습니다. 

NO3-는 

약 12~40분 범위에서 가장 큰 효과가 있을 것으로 예상됩니다. 

또한, 이 시간 범위 내에서 NO3- 보충제의 효과는 

601~999초(~10~17분) 동안 지속되는 운동에서 가장 두드러지며, 

정상 산소 또는 저산소 상태에 관계없이 효과적입니다[84].

NO3- 보충제의 효과는 다양한 성능 테스트에서 연구되었습니다. 그러나 그 효과는 타임 트라이얼 테스트나 증분 파워 테스트보다는 시간 대비 탈진 테스트에서 특히 두드러지게 나타났습니다. 이는 탈진까지의 시간 테스트가 선수의 지구력 능력을 측정하는 데 더 적합하고 심리적 요인(예: 동기 부여, 지루함 등)의 영향을 많이 받는 것으로 추정되기 때문일 수 있습니다[3,86]. 운동 유형과 관련하여 Senefeld 등(2020)은 NO3- 보충에 관한 연구에서 가장 일반적으로 연구되는 훈련 방식인 사이클링과 달리기에는 NO3-가 유의미한 효과를 보이지만 무릎 확장 테스트나 조정 휴식에는 영향을 미치지 않는다고 보고했습니다. 그러나 이러한 효과의 부족은 운동 유형 자체보다는 이 두 가지 형태의 운동 능력 테스트에 대한 연구 비율이 상대적으로 낮기 때문일 가능성이 높습니다 [84].

NO3-는 인지에 잠재적으로 유익한 효과가 있기 때문에 팀 스포츠 운동선수에게 특히 효과적일 수 있습니다. 팀 스포츠에 참가하는 선수는 훈련과 경기 중에 많은 결정을 빠르게 내려야 합니다. 그러나 장시간의 고강도 운동은 반응 시간과 과제 수행에 부정적인 영향을 미칠 수 있습니다 [87]. 톰슨 등(2015)은 7일 연속으로 6.4mmol~12.8mmol의 NO3 보충제를 섭취한 사람의 반응 시간이 통계적으로 유의하게 짧아졌다고 보고했습니다[88]. NO3- 보충제가 인지에 미치는 이러한 긍정적인 효과는 신경 혈관 결합에 대한 NO의 긍정적인 효과 [89]와 주로 실행 기능을 담당하는 전전두엽 피질의 뇌 관류 증가 [90]에서 비롯된 것일 수 있습니다. 따라서 NO3-는 반복적인 고강도 간헐적 운동과 관련된 인지 기능, 주로 운동선수의 반응 시간 저하를 줄이는 데 잠재적으로 긍정적인 영향을 미칠 수 있습니다.

NO3 보충제가 운동 능력에 미치는 영향에 대한 대부분의 연구는 지구력 테스트를 통해 이루어졌습니다. 그러나 일부 연구는 고강도 운동과 근력에 대한 이러한 효과를 조사하는 데 초점을 맞추고 있으며, 그 결과도 엇갈리는 것으로 나타났습니다. 톰슨 등(2016)은 NO3 보충제 섭취 후 요요 테스트에서 스프린트가 개선되었다고 보고했습니다[91]. 32명의 축구 선수 표본을 대상으로 한 동일한 테스트에서도 비슷한 효과가 보고되었습니다 [24]. (2018)은 또한 Wingate 테스트에서 주로 스프린트 전반부에 6.4 mmol의 급성 NO3- 섭취의 에르고 제닉 효과를보고했습니다 [50]. 그러나 Martin 등(2014)은 30초 휴식과 8초 스프린트 프로토콜에 대한 NO3-의 긍정적 효과를 보고하지 않았습니다[43].

4개의 제한된 연구 표본에서 웨이트 트레이닝에 대한 NO3-의 효과에 대한 San Juan 등(2020)의 체계적 검토에서는 상체 근력 테스트(벤치 프레스)와 하체 근력 테스트(스쿼트)에서 수행된 반복 횟수에 대한 NO3-의 긍정적인 효과가 보고되었습니다 [92]. 고강도 운동과 근력에 대한 NO3-의 영향에 대해서는 더 많은 연구가 필요하지만, 예비 결과에 따르면 NO3-는 이러한 스포츠 상황에서도 유익할 수 있다고 합니다.

NO3-가 운동 능력에 미치는 또 다른 영향은 저산소 및 추운 환경(예: 등산, 스키, 고산 훈련 등)과 같은 극한 조건에서 수행된 연구입니다. 고도가 높아질수록 저산소 상태는 산소 가용성을 감소시키고 운동 능력을 저하시킵니다. 고도 적응을 통해 이 문제를 어느 정도 극복할 수 있지만, 이 과정이 완전히 나타나기까지 최대 몇 주가 걸릴 수 있으며 특정 스포츠 상황에서는 항상 가능한 것은 아닙니다. 또한, 장기간의 적응에도 불구하고 해수면에서의 체력이 완전히 회복되지 않을 수도 있습니다[93]. NO는 저산소증으로 인한 혈관 확장에 필수적인 역할을 하여 저산소 상태에서 작동하는 근육과 뇌 조직에 적절한 산소 가용성을 보장하는 것으로 알려져 있습니다 [94,95]. 높은 고도에 서식하는 특정 집단(예: 셰르파)은 부분적으로 순환하는 NO 수치가 높아 비정상적인 저산소 내성을 발휘하는 것으로 제안되었습니다 [96]. 실제로 시뮬레이션 고도에서 수행된 연구에 따르면 NO3 보충제가 특정 생리적 매개변수(예: 미토콘드리아 호흡 개선, 운동 중 산소 소비량 등)에 미치는 이점이 있는 것으로 나타났습니다. 그러나 이러한 결과는 '실제' 고도에서의 현장 테스트에서는 관찰되지 않아 실제 적용에는 한계가 있는 것으로 보입니다 [93,96,97]. 일부 연구자들은 동맥 및 근육 산소 포화도를 감소시켜 저산소 적응을 무디게 할 수 있다는 관점에서 만성 NO3- 보충제가 고지에서 훈련하는 운동선수에게 해로울 수 있다고 가정했으며, 이는 그러한 적응의 신호로 작용할 수 있습니다 [98]. 따라서 현재로서는 높은 고도에서 운동하는 운동선수에게 NO3 보충제의 명확한 이점은 없으며, 이 특정 주제에 대한 더 많은 연구가 필요합니다.

2.3. Nitrates: Food Sources and Supplementation

The primary sources of NO3− and NO2− is either through NO3− rich foods or through endogenous productions. Of these pathways, nutrition represents the one with greater potential to supply the body with a higher amount of NO3− as the endogenous supply of NO3− is relatively limited, and only a bowl of green leafy vegetables contains a higher amount of NO3− than is formed endogenously throughout the entire day [9]. Athletes should thus be advised to meet their NO3− through nutrition, either with NO3− supplementation or through NO3− rich foods—primarily leafy greens and root vegetables.

However, the NO3− content of these vegetables varies greatly, as it depends on many factors such as the origin of the vegetable, the quality and pH of the soil in which the vegetables are grown, type and frequency of nitrogen fertilizers, type of vegetable cultivation, time of vegetable harvesting, age of the plant at harvest, conditions of vegetable storage and weather conditions in which vegetables are grown, and method of vegetable preparation, etc. [99].

Given all these factors, it is difficult to make a specific recommendation for athletes to meet the needs of NO3− via the diet due to the large number of variable factors that affect the NO3− content in the diet. Speculations can be made based on current data on the average NO3− of NO3− rich foods (e.g., beetroot, endive, fennel, kohlrabi, lettuce, pak choi, radish, rocket, and spinach) that this figure would be set at 150 g of aforementioned foods at the lowest [100]. However, this number might be significantly higher or possibly lower in some cases, depending on the above-mentioned factors. As a higher vegetable intake than 150 g is generally recommended, athletes should probably be encouraged to ingest approximately 250–500 g of leafy and root vegetables per day to ensure adequate NO3− intake.

Additionally, ingesting a bolus of NO3− via supplementation might hold a greater risk of peroxynitrite production relative to covering NO3− needs through diet. This might be another limiting factor of NO3− supplementation, as discussed in the chapter titled ’Nitrates and exercise performance’.

Lastly, NO3− in the form of a dietary supplement may represent a more convenient and accurate way to cover the needs for NO3−; however, as with any other dietary supplement, there is always the possibility of supplement contamination [101], and an athlete’s budget must also be considered.

NO3-와 NO2-의 주요 공급원은 

NO3-가 풍부한 식품 또는 

내인성 생성을 통한 것입니다. 

이러한 경로 중 영양 섭취는 

내인성 공급이 상대적으로 제한적이며 

녹색 잎채소 한 그릇에만 하루 종일 내인성 생성되는 것보다 

더 많은 양의 NO3-를 함유하고 있기 때문에 

더 많은 양의 NO3-를 체내에 공급할 가능성이 더 큰 경로입니다 [9]. 

따라서 

운동선수는 

NO3- 보충제나 NO3-가 풍부한 식품(주로 잎채소와 뿌리채소)을 통해 영양 섭취를 통해 

NO3-를 충족하는 것이 좋습니다.

그러나 

이러한 채소의 NO3- 함량은 

채소의 원산지, 채소가 재배되는 토양의 질과 pH, 질소 비료의 종류와 빈도, 

채소 재배 유형, 채소 수확 시기, 수확 시 식물의 나이, 채소 저장 조건 및 채소가 재배되는 기상 조건, 

채소 조리 방법 등과 같은 여러 요인에 따라 크게 달라집니다. [99].

이러한 모든 요인을 고려할 때, 

식단에서 NO3- 함량에 영향을 미치는 다양한 요인으로 인해 

운동선수에게 식단을 통해 

NO3-의 필요를 충족시키기 위한 구체적인 권장 사항을 제시하기는 어렵습니다. 

NO3- 가 풍부한 식품(예: 비트, 엔다이브, 회향, 콜라비, 상추, 박초, 무, 로켓, 시금치)의 

평균 NO3- 에 대한 현재 데이터를 기반으로 추측할 수 있는 수치는 

앞서 언급한 식품을 가장 적게는 150g에서 가장 높게 설정할 수 있다는 것입니다[100]. 

그러나 위에서 언급한 요인에 따라 이 수치는 경우에 따라 훨씬 더 높거나 낮을 수도 있습니다. 일반적으로 150g보다 더 많은 양의 채소를 섭취하는 것이 권장되므로 운동선수는 적절한 NO3 섭취를 위해 하루에 약 250~500g의 잎채소와 뿌리채소를 섭취하는 것이 좋습니다.

또한, 보충제를 통해 NO3-를 대량으로 섭취하면 식단을 통해 NO3- 필요량을 충족하는 것보다 과산화아질산염 생성 위험이 더 커질 수 있습니다. 이는 '질산염과 운동 수행 능력'이라는 장에서 설명한 것처럼 NO3- 보충제의 또 다른 제한 요인일 수 있습니다.

마지막으로, 식이 보충제 형태의 NO3-는 NO3-의 필요량을 충족하는 데 더 편리하고 정확한 방법이 될 수 있지만, 다른 식이 보충제와 마찬가지로 항상 보충제 오염 가능성이 있으며[101], 운동선수의 예산도 고려해야 합니다.

3. Conclusions

Based on current literature, NO3− represents an effective ergogenic aid for improving performance through various mechanisms and is useful in a variety of sports situations and exercise modalities. The effect of NO3− is most pronounced in less-trained individuals when taken acutely or chronically in the range of ~5–16.8 mmol (~300–1041 mg NO3−) 2–3 h before exercise and primarily in the case of exercise duration of ~10–17 min. Nitrate supplementation is less pronounced in well-trained individuals (VO2max > 65 mL/kg/min); however, it might still be desirable, especially during competition. Athletes should refrain from mouthwash usage when nitrate supplementation benefits are desired.

NO3− is found in certain vegetables, but due to many variable factors, we cannot make exact recommendations to cover these needs through diet alone. Given that there is a potential for supplement contamination, it would make sense to explore how dietary needs for NO3− can be covered through dietary sources. Currently, speculations can be made that this figure is roughly 250–500 g of leafy and root vegetables per day. Dietary supplements might represent a more convenient and accurate way of covering one’s needs for nitrate; however, potential supplement contamination and an athlete’s budget must be considered.

Future research should focus on the potential beneficial effects of NO3− on the brain, especially in regard to sport-specific situations, and on the effectiveness of NO3− in strength training and high-intensity intermittent training.

현재 문헌에 따르면 

NO3-는 

다양한 메커니즘을 통해 운동 능력을 향상시키는 데 효과적인

 에르고제닉 보조제로서 

다양한 스포츠 상황과 운동 방식에 유용합니다. 

NO3-의 효과는 

운동 2~3시간 전에 ~5-16.8mmol(~300-1041mg NO3-)의 범위에서 

급성 또는 만성적으로 섭취할 때, 

그리고 주로 운동 시간이 ~10-17분인 경우에 훈련이 덜 된 사람에게 

가장 두드러지게 나타남을 알 수 있습니다. 

질산염 보충제는 

잘 훈련된 사람(VO2max > 65mL/kg/min)에게는 그 효과가 덜하지만, 

특히 경기 중에는 질산염 보충제를 섭취하는 것이 바람직할 수 있습니다. 

운동선수는 질산염 보충제의 효과를 원할 때 구강 청결제 사용을 자제해야 합니다.

NO3-는 특정 채소에 많이 함유되어 있지만, 

다양한 요인으로 인해 식단만으로 이러한 필요량을 충족하기 위한 정확한 권장량을 제시할 수는 없습니다. 

보충제의 오염 가능성이 있다는 점을 고려할 때, 

식이 공급원을 통해 NO3-의 필요량을 충족할 수 있는 방법을 모색하는 것이 합리적일 것입니다. 

현재로서는 

하루에 대략 250~500g의 잎채소와 뿌리채소를 섭취하면 

이 수치를 충족할 수 있을 것으로 추측할 수 있습니다. 

식이 보충제는 

질산염에 대한 필요량을 충족하는 더 편리하고 정확한 방법이 될 수 있지만, 

보충제의 오염 가능성과 운동선수의 예산을 고려해야 합니다.

향후 연구는 특히 스포츠별 상황과 관련하여 

NO3-가 뇌에 미치는 잠재적인 유익한 효과와 근력 운동 및 고강도 간헐적 훈련에서 NO3-의 효과에 초점을 맞추어야 합니다.

Author Contributions

Conceptualization, M.M. and B.K.; methodology, M.M.; validation, M.M. and B.K.; formal analysis, M.M.; investigation, M.M.; resources, M.M.; data curation, M.M.; writing—original draft preparation, M.M.; writing—review and editing, M.M.; visualization, B.K.; supervision, B.K.; project administration, B.K.; funding acquisition, B.K. All authors have read and agreed to the published version of the manuscript.

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Funding

This research received no external funding.

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Institutional Review Board Statement

Not applicable.

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Informed Consent Statement

Not applicable.

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Conflicts of Interest

The authors declare no conflict of interest.

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Footnotes

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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[문형철]

https://academic.oup.com/pmj/article/98/1158/285/6958842

질산염(산화질소) 불면에도 효과있음