Exercise-related menstrual dysfunction (ExMD) is associated with low energy availability (EA), decreased bone mineral density (BMD), and increased risk of musculoskeletal injury. We investigated whether a 6-month carbohydrate-protein (CHO-PRO) supplement (360 kcal/day, 54 g CHO/day, 20 g PRO/day) intervention would improve energy status and musculoskeletal health and restore menses in female athletes (n = 8) with ExMD. At pre/post-intervention, reproductive and thyroid hormones, bone health (BMD, bone mineral content, bone markers), muscle strength/power and protein metabolism markers, profile of mood state (POMS), and energy intake (EI)/energy expenditure (7 day food/activity records) were measured. Eumenorrheic athlete controls with normal menses (Eumen); n = 10) were measured at baseline. Multiple linear regressions were used to evaluate differences between groups and pre/post-intervention blocking on participants. Improvements in EI (+382 kcal/day; p = 0.12), EA (+417 kcal/day; p = 0.17) and energy balance (EB; +466 kcal/day; p = 0.14) were observed with the intervention but were not statistically significant. ExMD resumed menses (2.6 ± 2.2-months to first menses; 3.5 ± 1.9 cycles); one remaining anovulatory with menses. Female athletes with ExMD for >8 months took longer to resume menses/ovulation and had lower BMD (low spine (ExMD = 3; Eumen = 1); low hip (ExMD = 2)) than those with ExMD for <8 months; for 2 ExMD the intervention improved spinal BMD. POMS fatigue scores were 15% lower in ExMD vs. Eumen (p = 0.17); POMS depression scores improved by 8% in ExMD (p = 0.12). EI, EA, and EB were similar between groups, but the intervention (+360 kcal/day) improved energy status enough to reverse ExMD despite no statistically significant changes in EI. Similar baseline EA and EB between groups suggests that some ExMD athletes are more sensitive to EA and EB fluctuations.

Quercetin (Q) and green tea extract (E) are reported to counter insulin resistance and inflammation and favorably alter fat metabolism. We investigated whether a mixture of E + Q (EQ) could synergistically influence metabolic and inflammation endpoints in a high-fat diet (HFD) fed to mice. Male C57BL/6 mice (n = 40) were put on HFD (fat = 60%kcal) for 12 weeks and randomly assigned to Q (25 mg/kg of body weight (BW)/day), E (3 mg of epigallocatechin gallate/kg BW/day), EQ, or control groups for four weeks. At 16 weeks, insulin sensitivity was measured via the glucose tolerance test (GTT), followed by area-under-the-curve (AUC) estimations. Plasma cytokines and quercetin were also measured, along with whole genome transcriptome analysis and real-time polymerase chain reaction (qPCR) on adipose, liver, and skeletal muscle tissues. Univariate analyses were conducted via analysis of variance (ANOVA), and whole-genome expression profiles were examined via gene set enrichment. At 16 weeks, plasma quercetin levels were higher in Q and EQ groups vs. the control and E groups (p < 0.05). Plasma cytokines were similar among groups (p > 0.05). AUC estimations for GTT was 14% lower for Q vs. E (p = 0.0311), but non-significant from control (p = 0.0809). Genes for cholesterol metabolism and immune and inflammatory response were downregulated in Q and EQ groups vs. control in adipose tissue and soleus muscle tissue. These data support an anti-inflammatory role for Q and EQ, a result best captured when measured with tissue gene downregulation in comparison to changes in plasma cytokine levels.

Flavonoids and fish oils have anti-inflammatory and immune-modulating influences. The purpose of this study was to determine if a mixed flavonoid-fish oil supplement (Q-Mix; 1000 mg quercetin, 400 mg isoquercetin, 120 mg epigallocatechin (EGCG) from green tea extract, 400 mg n3-PUFAs (omega-3 polyunsaturated fatty acid) (220 mg eicosapentaenoic acid (EPA) and 180 mg docosahexaenoic acid (DHA)) from fish oil, 1000 mg vitamin C, 40 mg niacinamide, and 800 µg folic acid) would reduce complications associated with obesity; that is, reduce inflammatory and oxidative stress markers and alter genomic profiles in overweight women. Overweight and obese women (n = 48; age = 40–70 years) were assigned to Q-Mix or placebo groups using randomized double-blinded placebo-controlled procedures. Overnight fasted blood samples were collected at 0 and 10 weeks and analyzed for cytokines, C-reactive protein (CRP), F₂-isoprostanes, and whole-blood-derived mRNA, which was assessed using Affymetrix HuGene-1_1 ST arrays. Statistical analysis included two-way ANOVA models for blood analytes and gene expression and pathway and network enrichment methods for gene expression. Plasma levels increased with Q-Mix supplementation by 388% for quercetin, 95% for EPA, 18% for DHA, and 20% for docosapentaenoic acid (DPA). Q-Mix did not alter plasma levels for CRP (p = 0.268), F2-isoprostanes (p = 0.273), and cytokines (p > 0.05). Gene set enrichment analysis revealed upregulation of pathways in Q-Mix vs. placebo related to interferon-induced antiviral mechanism (false discovery rate, FDR < 0.001). Overrepresentation analysis further disclosed an inhibition of phagocytosis-related inflammatory pathways in Q-Mix vs. placebo. Thus, a 10-week Q-Mix supplementation elicited a significant rise in plasma quercetin, EPA, DHA, and DPA, as well as stimulated an antiviral and inflammation whole-blood transcriptomic response in overweight women.

Female athletes who follow a diet that fails to meet energy and nutrient needs are at risk for musculoskeletal injuries, menstrual disturbances, and poor sports performance. Common nutritional concerns for the female athlete include low energy availability (EA) (i.e., energy intake from food remaining for metabolic processes after accounting for energy expended during exercise) and inadequate dietary intakes (i.e., not meeting sports nutrition guidelines) of carbohydrates, protein, essential fatty acids (EFAs), B-vitamins, calcium, iron, and vitamin D. Low EA and the associated nutrient deficiencies are more common in athletes who compete in weight-sensitive sports (i.e., aesthetic, gravitational, and weight category sports) because low body fat and mass confer a competitive advantage. Other athletes at risk for energy and nutrient deficits include athletes following a vegetarian or gluten-free diet (GFD). Careful dietary planning can help an athlete meet energy and nutrient needs. This review covers the nutrition issues associated with low EA and special diets (i.e., vegetarian and GFD) and describes strategies to help female athletes meet their energy and nutrient needs.

Low energy availability (EA) (e.g., insufficient energy intake (EI) to match energy needs, including exercise energy expenditure) has been identified as a primary contributor to exercise-associated menstrual dysfunction (ExMD) in active women. For health reasons, active women may self-select diets lower in energy density (ED, kcal/g), which can inadvertently contribute to inadequate EI. Using data from two studies, we compared the ED of active women with ExMD (n = 9; 24 ± 6 years) to eumenorrheic (EU) active controls (EU: n = 18, 27 ± 6 years). ED was calculated from 6 to 7 days weighted food records using two methods: with/without beverages. ANOVA and Wilcoxon Rank-Sum were used to test group differences. ED was not different between groups, but there was a trend toward a lower median ED (10%) (p = 0.049 unadjusted; p = 0.098 adjusted) in the ExMD-group (Method 1—all beverages: ExMD = 1.01 kcal/g (range = 0.52–1.41), EU = 1.22 kcal/g (range = 0.72–1.72); Method 2—without beverages: ExMD = 1.51 kcal/g (range = 1.26–2.06), EU = 1.69 kcal/g (range = 1.42–2.54)). This lower ED represents a 9% decrease (~219 kcal/day) in EI (ExMD = 2237 ± 378 kcal/day; EU = 2456 ± 470 kcal/day; p > 0.05). EI and macro/micronutrient intakes were similar for groups. In the ExMD-group, low ED could contribute to lower EI and EA. Future research should examine the interaction of ED and exercise on appetite, EI, and EA in active women, especially those with ExMD.