Moving beyond inclusion: methodological considerations for menstrual cycle and menopause in research evaluating the effects of dietary nitrate on vascular function

Black women (BLW) have a higher prevalence of cardiovascular disease (CVD) morbidity and mortality compared to white women (WHW). A racial disparity in CVD risk has been identified early in life as young adult BLW demonstrate attenuated vascular function compared to WHW. Previous studies comparing vascular function between premenopausal WHW and BLW have been limited to the early follicular (EF) phase of the menstrual cycle, which may not reflect their vascular function during other menstrual phases. Therefore, we evaluated peripheral microvascular function in premenopausal WHW and BLW using passive leg movement (PLM) during three menstrual phases: EF, ovulation (OV), and mid-luteal (ML). We hypothesized that microvascular function would be augmented during the OV and ML phases compared to the EF phase in both groups, but would be attenuated in BLW compared to WHW at all three phases. PLM was performed on 26 apparently healthy premenopausal women not using hormonal contraceptives: 15 WHW (23±3 years), 11 BLW (24±5 years). There was a main effect of race on the overall change in leg blood flow (∆LBF) (p=0.01) and leg blood flow area under the curve (LBF AUC) (p=0.02), such that LBF was lower in BLW. However, there was no effect of phase on ∆LBF (p=0.69) or LBF AUC (p=0.65), nor an interaction between race and phase on ∆LBF (p=0.37) or LBF AUC (p=0.75). Despite peripheral microvascular function being unchanged across the menstrual cycle, a racial disparity was apparent as microvascular function was attenuated in BLW compared to WHW across the menstrual cycle.

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Impact of the menstrual cycle on peripheral vascular function in premenopausal women: systematic review and meta-analysis

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00341.2020 ◽

2020 ◽

Vol 319 (6) ◽

pp. H1327-H1337

Author(s):

Jennifer S. Williams ◽

Emily C. Dunford ◽

Maureen J. MacDonald

Keyword(s):

Systematic Review ◽

Menstrual Cycle ◽

Endothelial Function ◽

Vascular Function ◽

Meta Analysis ◽

Premenopausal Women ◽

Cycle Phase ◽

Peripheral Vascular ◽

The Impact

Fluctuations in endogenous hormones estrogen and progesterone during the menstrual cycle may offer vasoprotection for endothelial and smooth muscle (VSM) function. While numerous studies have been published, the results are conflicting, leaving our understanding of the impact of the menstrual cycle on vascular function unclear. The purpose of this systematic review and meta-analysis was to consolidate available research exploring the role of the menstrual cycle on peripheral vascular function. A systematic search of MEDLINE, Web of Science, and EMBASE was performed for articles evaluating peripheral endothelial and VSM function across the natural menstrual cycle: early follicular (EF) phase versus late follicular (LF), early luteal, mid luteal, or late luteal. A meta-analysis examined the effect of the menstrual cycle on the standardized mean difference (SMD) of the outcome measures. Analysis from 30 studies ( n = 1,363 women) observed a “very low” certainty of evidence that endothelial function increased in the LF phase (SMD: 0.45, P = 0.0001), with differences observed in the macrovasculature but not in the microvasculature (SMD: 0.57, P = 0.0003, I2 = 84%; SMD: 0.21, P = 0.17, I2 = 34%, respectively). However, these results are partially explained by differences in flow-mediated dilation [e.g., discrete (SMD: 0.86, P = 0.001) vs. continuous peak diameter assessment (SMD: 0.25, P = 0.30)] and/or menstrual cycle phase methodologies. There was a “very low” certainty that endothelial function was largely unchanged in the luteal phases, and VSM was unchanged across the cycle. The menstrual cycle appears to have a small effect on macrovascular endothelial function but not on microvascular or VSM function; however, these results can be partially attributed to methodological differences.

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Dietary nitrate supplementation: impact on skeletal muscle vascular control in exercising rats with chronic heart failure

Journal of Applied Physiology ◽

10.1152/japplphysiol.00014.2016 ◽

2016 ◽

Vol 121 (3) ◽

pp. 661-669 ◽

Cited By ~ 24

Author(s):

Scott K. Ferguson ◽

Clark T. Holdsworth ◽

Trenton D. Colburn ◽

Jennifer L. Wright ◽

Jesse C. Craig ◽

...

Keyword(s):

Myocardial Infarction ◽

Heart Failure ◽

Skeletal Muscle ◽

Mean Arterial Pressure ◽

Chronic Heart Failure ◽

Arterial Pressure ◽

Vascular Function ◽

Left Ventricular ◽

Male Rats ◽

Dietary Nitrate

Chronic heart failure (CHF) results in central and peripheral derangements that ultimately reduce skeletal muscle O2 delivery and impair exercise tolerance. Dietary nitrate (NO3−) supplementation improves skeletal muscle vascular function and tolerance to exercise. We tested the hypothesis that NO3− supplementation would elevate exercising skeletal muscle blood flow (BF) and vascular conductance (VC) in CHF rats. Myocardial infarction (MI) was induced (coronary artery ligation) in young adult male rats. After 21 days of recovery, rats randomly received 5 days of NO3−-rich beetroot juice (CHF + BR, n = 10) or a placebo (CHF, n = 10). Mean arterial pressure (carotid artery catheter) and skeletal muscle BF (radiolabeled microspheres) were measured during treadmill exercise (20 m/min, 5% grade). CHF-induced dysfunction, as determined by myocardial infarction size (29 ± 3% and 33 ± 4% in CHF and CHF + BR, respectively) and left ventricular end-diastolic pressure (18 ± 2 and 18 ± 2 mmHg in CHF and CHF + BR, respectively), and exercising mean arterial pressure (131 ± 3 and 128 ± 4 mmHg in CHF and CHF + BR, respectively) were not different ( P > 0.05) between groups. Total exercising hindlimb skeletal muscle BF (95 ± 5 and 116 ± 9 ml·min−1·100 g−1 in CHF and CHF + BR, respectively) and VC (0.75 ± 0.05 and 0.90 ± 0.05 ml·min−1·100 g−1·mmHg−1 in CHF and CHF + BR, respectively) were 22% and 20% greater in BR-supplemented rats, respectively ( P < 0.05). During exercise, BF in 9 and VC in 10 hindlimb muscles and muscle portions were significantly greater in the CHF + BR group. These results provide strong evidence that dietary NO3− supplementation improves skeletal muscle vascular function during exercise in rats with CHF and, thus, support the use of BR as a novel therapeutic modality for the treatment of CHF.

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The Role of Dietary Nitrate and the Oral Microbiome on Blood Pressure and Vascular tone

Nutrition Research Reviews ◽

10.1017/s0954422420000281 ◽

2020 ◽

pp. 1-53

Author(s):

H.S. Alzahrani ◽

K.G. Jackson ◽

D.A. Hobbs ◽

J.A. Lovegrove

Keyword(s):

Blood Pressure ◽

Vascular Function ◽

Vascular Tone ◽

Cardiovascular Health ◽

Oral Bacteria ◽

Oral Microbiome ◽

Current Evidence ◽

Dietary Nitrate ◽

Beneficial Effects

Abstract There is increasing evidence for the health benefits of dietary nitrates including lowering blood pressure and enhancing cardiovascular health. Although commensal oral bacteria play an important role in converting dietary nitrate to nitrite, very little is known about the potential role of these bacteria in blood pressure regulation and maintenance of vascular tone. The main purpose of this review is to present the current evidence on the involvement of the oral microbiome in mediating the beneficial effects of dietary nitrate on vascular function and to identify sources of inter and intra-individual differences in bacterial composition. A systematic approach was used to identify the relevant articles published on PubMed and Web of Science in English from January 1950 until September 2019 examining the effects of dietary nitrate on oral microbiome composition and association with blood pressure and vascular tone. To date, only a limited number of studies have been conducted, with n=9 in humans and n=3 in animals focusing mainly on blood pressure. In general, elimination of oral bacteria with use of a chlorhexidine based antiseptic mouthwash reduced the conversion of nitrate to nitrite and was accompanied in some studies by an increase in blood pressure in normotensive subjects. In conclusion, our findings suggest that oral bacteria may play an important role in mediating the beneficial effects of nitrate-rich foods on blood pressure. Further human intervention studies assessing the potential effects of dietary nitrate on oral bacteria composition and relationship to real time measures of vascular function are needed, particularly in individuals with hypertension and those at risk of developing cardiovascular diseases.

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Potential Racial Disparity In Peripheral Vascular Function Regardless Of Menstrual Cycle Phase

Medicine & Science in Sports & Exercise ◽

10.1249/01.mss.0000670100.87234.05 ◽

2020 ◽

Vol 52 (7S) ◽

pp. 13-13

Author(s):

Michele N. D'Agata ◽

Alexandra E. Hirt ◽

Elissa K. Katulka ◽

Felicia R. Berube ◽

Megan M. Wenner ◽

...

Keyword(s):

Menstrual Cycle ◽

Racial Disparity ◽

Vascular Function ◽

Cycle Phase ◽

Peripheral Vascular ◽

Menstrual Cycle Phase

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Blunted Hyperemic Response to Mental Stress in Young, Non-Hispanic Black Men is not Impacted by Acute Dietary Nitrate Supplementation

Journal of Applied Physiology ◽

10.1152/japplphysiol.00453.2020 ◽

2021 ◽

Author(s):

John D. Akins ◽

Bryon M. Curtis ◽

Jordan C. Patik ◽

Guillermo Olvera ◽

Aida Nasirian ◽

...

Keyword(s):

Blood Flow ◽

Vascular Function ◽

Mental Stress ◽

Forearm Blood Flow ◽

Phase 1 ◽

Nitrate Content ◽

Phase 2 ◽

Dietary Nitrate ◽

Nitrate Supplementation ◽

No Bioavailability

Non-Hispanic black individuals have an elevated prevalence of cardiovascular disease in large part, related to impaired vascular function, secondary to reduced nitric oxide (NO) bioavailability. Nitrate supplementation increases NO bioavailability and improves vascular function. This study tested the hypothesis that forearm blood flow responses in young, non-Hispanic, black (BL) men during mental stress are blunted relative to, non-Hispanic, white (WH) men and that acute dietary nitrate supplementation would improve this response in BL men. This study was comprised of two parts. Phase 1 investigated the blood flow responses between young, BL and WH men whereas Phase 2 investigated the effect of acute nitrate supplementation in a subset of the BL men. Eleven (9 for Phase 2) BL and 8 WH men (23 ± 3 vs. 24 ± 4 y, respectively) participated. During each visit, brachial artery blood flow was assessed during 3 min of mental stress. Phase 1 was completed in one visit, while Phase 2 was completed over two visits separated by ~1-wk. During Phase 2, data were collected before and 2-h post-consumption of a beverage high in nitrate content or nitrate depleted. In Phase 1, peak forearm blood flow (FBF, P < 0.01), total FBF (P < 0.05), and forearm vascular conductance (P < 0.001) were blunted in the BL. During Phase 2, pre-beverage responses were unaffected following beverage consumption (P > 0.05 for all). Young, BL men have blunted microvascular vasodilatory responses to acute mental stress, which may not be altered following acute nitrate supplementation.

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Investigating the effects of dietary nitrate on vascular function, platelet reactivity and restenosis in patients with stable angina

http://isrctn.com/ ◽

10.1186/isrctn17373946 ◽

2015 ◽

Author(s):

Krishnaraj Rathod

Keyword(s):

Stable Angina ◽

Vascular Function ◽

Platelet Reactivity ◽

Dietary Nitrate

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Recommendations and Nutritional Considerations for Female Athletes: Health and Performance

Sports Medicine ◽

10.1007/s40279-021-01508-8 ◽

2021 ◽

Author(s):

Bryan Holtzman ◽

Kathryn E. Ackerman

Keyword(s):

Menstrual Cycle ◽

Female Athletes ◽

Sports Science ◽

Specific Effects ◽

Optimal Health ◽

Menstrual Patterns ◽

And Performance ◽

Methodological Considerations ◽

Hormonal Milieu ◽

Future Work

AbstractOptimal nutrition is an important aspect of an athlete’s preparation to achieve optimal health and performance. While general concepts about micro- and macronutrients and timing of food and fluids are addressed in sports science, rarely are the specific effects of women’s physiology on energy and fluid needs highly considered in research or clinical practice. Women differ from men not only in size, but in body composition and hormonal milieu, and also differ from one another. Their monthly hormonal cycles, with fluctuations in estrogen and progesterone, have varying effects on metabolism and fluid retention. Such cycles can change from month to month, can be suppressed with exogenous hormones, and may even be manipulated to capitalize on ideal timing for performance. But before such physiology can be manipulated, its relationship with nutrition and performance must be understood. This review will address general concepts regarding substrate metabolism in women versus men, common menstrual patterns of female athletes, nutrient and hydration needs during different phases of the menstrual cycle, and health and performance issues related to menstrual cycle disruption. We will discuss up-to-date recommendations for fueling female athletes, describe areas that require further exploration, and address methodological considerations to inform future work in this important area.

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