J. Philip Karl

Randomized, double-blind, placebo-controlled trial of iron supplementation in female soldiers during military training: effects on iron status, physical performance, and mood

BACKGROUND Decrements in iron status have been reported in female soldiers during military training. Diminished iron status adversely affects physical and cognitive performance. OBJECTIVE We wanted to determine whether iron supplementation could prevent decrements in iron status and improve measures of physical performance and cognitive status in female soldiers during basic combat training (BCT). DESIGN In this 8-wk randomized, double-blind, placebo-controlled trial, soldier volunteers (n = 219) were provided with capsules containing either 100 mg ferrous sulfate or a placebo. Iron status indicator assays were performed pre- and post-BCT. Two-mile running time was assessed post-BCT; mood was assessed by using the Profile of Mood States questionnaire pre- and post-BCT. RESULTS The BCT course affected iron status: red blood cell distribution width and soluble transferrin receptor were elevated (P < 0.05), and serum ferritin was lowered (P < 0.05) post-BCT. Iron supplementation attenuated the decrement in iron status; group-by-time interactions (P < 0.01) were observed for serum ferritin and soluble transferrin receptor. Iron supplementation resulted in improved (P < 0.05) vigor scores on the Profile of Mood States post-BCT and in faster running time (P < 0.05) in volunteers reporting to BCT with iron deficiency anemia. CONCLUSIONS Iron status is affected by BCT, and iron supplementation attenuates the decrement in indicators of iron status in female soldiers. Furthermore, iron supplementation may prove to be beneficial for mood and physical performance during the training period. Future efforts should identify and treat female soldiers or athletes who begin training regimens with iron deficiency or iron deficiency anemia.

Iron deficiency and obesity: the contribution of inflammation and diminished iron absorption

Poor iron status affects billions of people worldwide. The prevalence of obesity continues to rise in both developed and developing nations. An association between iron status and obesity has been described in children and adults. The mechanism explaining this relationship remains unknown; however, findings from recent reports suggest that body mass index and inflammation predict iron absorption and affect the response to iron fortification. The relationship between inflammation and iron absorption may be mediated by hepcidin, although further studies will be required to confirm this potential physiological explanation for the increased prevalence of iron deficiency in the obese.

Nutrient Deficiencies After Gastric Bypass Surgery

Bariatric surgery, and in particular, gastric bypass, is an increasingly utilized and successful approach for long-term treatment of obesity and amelioration of comorbidities. Nutrient deficiencies after surgery are common and have multiple causes. Preoperative factors include obesity, which appears to be associated with risk for several nutrient deficiencies, and preoperative weight loss. Postoperatively, reduced food intake, suboptimal dietary quality, altered digestion and absorption, and nonadherence with supplementation regimens contribute to risk of deficiency. The most common clinically relevant micronutrient deficiencies after gastric bypass include thiamine, vitamin B₁₂, vitamin D, iron, and copper. Reports of deficiencies of many other nutrients, some with severe clinical manifestations, are relatively sporadic. Diet and multivitamin use are unlikely to consistently prevent deficiency, thus supplementation with additional specific nutrients is often needed. Though optimal supplement regimens are not yet defined, most micronutrient deficiencies after gastric bypass currently can be prevented or treated by appropriate supplementation.

Menaquinones, Bacteria, and the Food Supply: The Relevance of Dairy and Fermented Food Products to Vitamin K Requirements

Vitamin K exists in the food supply as phylloquinone, a plant-based form and as menaquinones (MKs), a collection of isoprenologues mostly originating from bacterial synthesis. Although multiple bacterial species used as starter cultures for food fermentations synthesize MK, relatively little is known about the presence and distribution of MK in the food supply and the relative contribution of MK to total dietary vitamin K intake. Dairy products may be a predominant source of dietary MK in many regions of the world, and there is recent interest in enhancing the MK content of dairy products through identification and selection of MK-producing bacteria in dairy fermentations. This interest is increased by emerging evidence that current dietary recommendations based on the classic role of vitamin K as an enzyme cofactor for coagulation proteins may not be optimal for supporting vitamin K requirements in extrahepatic tissues and that MK may have unique bioactivity beyond that as an enzyme cofactor. Observational studies have reported favorable associations between MK intake and bone and cardiovascular health. Although randomized trials have provided some evidence to support the beneficial effects of MK on bone, the evidence to date is not definitive, and randomized trials have not yet examined MK intake in relation to cardiovascular outcomes. Food production practices provide a means to enhance dietary MK availability and intake. However, parallel research is needed to optimize these production practices, develop comprehensive food MK content databases, and test hypotheses of unique beneficial physiological roles of MK beyond that achieved by phylloquinone.

Randomized, double-blind, placebo-controlled trial of an iron-fortified food product in female soldiers during military training: relations between iron status, serum hepcidin, and inflammation

BACKGROUND Iron status degrades in female soldiers during military training. Inflammation-mediated up-regulation of hepcidin, a key mediator of iron homeostasis, may be a contributing factor. OBJECTIVE We measured the efficacy of an iron-fortified food product for maintaining iron status in female soldiers during basic combat training (BCT) and examined relations between iron status, serum hepcidin concentrations, and inflammation. DESIGN A randomized, double-blind, placebo-controlled trial was conducted. Volunteers received an iron-fortified food product (total dose = 56 mg Fe/d) or a placebo twice daily during the 9-wk BCT course. Iron-status indicators, serum hepcidin concentrations, and markers of inflammation were measured pre- and post-BCT. RESULTS BCT affected iron status; serum ferritin concentrations decreased (P < or = 0.05), and concentrations of soluble transferrin receptor (sTfR) and hemoglobin and the red cell distribution width increased (P < or = 0.05). Consumption of the iron-fortified food product attenuated declines in iron status in iron-deficient anemic soldiers; a group-by-time interaction was observed for hemoglobin and sTfR concentrations (P < or = 0.05). Serum hepcidin concentrations were not affected by BCT; however, hepcidin concentrations were lower in iron-deficient anemic soldiers than in those with normal iron status (P < or = 0.05) and were positively associated with serum ferritin (P < or = 0.05) and C-reactive protein (P < or = 0.05) concentrations pre- and post-BCT. CONCLUSIONS Twice-daily consumption of an iron-fortified food product improved iron status in iron-deficient anemic soldiers but not in iron-normal or iron-deficient nonanemic soldiers. Serum hepcidin concentrations were not affected by training but were associated with iron status and inflammation pre- and post-BCT. This trial was registered at clinicaltrials.gov as NCT01100905.

Longitudinal decrements in iron status during military training in female soldiers

Fe is an essential micronutrient required for optimal cognitive and physical performance. Cross-sectional studies indicate that training degrades Fe status in female military personnel; however, longitudinal studies to measure the direct impact of military training on Fe status and performance have not been conducted. As such, the objective of the present study was to determine the longitudinal effects of military training on Fe status in female soldiers. Fe status was assessed in ninety-four female soldiers immediately before and following a 9-week basic combat training (BCT) course. Fe status indicators included Hb, erythrocyte distribution width (RDW), serum ferritin, transferrin saturation and soluble transferrin receptor (sTfR). A 2-mile (3.2 km) run test was performed at the end of BCT to assess aerobic performance. Fe status was affected by BCT, as all Fe status indicators, excluding Hb, were diminished (P < or = 0.01) at the end of BCT. Fe status indicators at the end of BCT (Hb and RDW) were associated (P < or = 0.05) with running performance, as was the change in sTfR over the training period (r 0.320; P < or = 0.05). In conclusion, Fe status in female soldiers is degraded during BCT, and degraded Fe status is associated with diminished aerobic performance. Female athletes and military personnel should strive to maintain Fe status to optimise physical performance.

The Role of Whole Grains in Body Weight Regulation

Whole grain (WG)-rich diets are purported to have a variety of health benefits, including a favorable role in body weight regulation. Current dietary recommendations advocate substituting WG for refined grains (RG), because many of the beneficial bioactive components intrinsic to WG are lost during the refining process. Epidemiological studies consistently demonstrate that higher intakes of WG, but not RG, are associated with lower BMI and/or reduced risk of obesity. However, recent clinical trials have failed to support a role for WG in promoting weight loss or maintenance. Though the biochemical and structural characteristics of WG have been shown to modulate appetite, nutrient availability, and energy utilization, the capacity of WG foods to elicit these effects varies with the type and amount of grain consumed as well as the nature of its consumption. As such, WG foods differentially affect physiologic factors influencing body weight with the common practice of processing and reconstituting WG ingredients during food production likely mitigating the capacity for WG to benefit body weight regulation.

Substituting whole grains for refined grains in a 6-wk randomized trial has a modest effect on gut microbiota and immune and inflammatory markers of healthy adults

Background: Observational studies suggest an inverse association between whole-grain (WG) consumption and inflammation. However, evidence from interventional studies is limited, and few studies have included measurements of cell-mediated immunity.Objective: We assessed the effects of diets rich in WGs compared with refined grains (RGs) on immune and inflammatory responses, gut microbiota, and microbial products in healthy adults while maintaining subject body weights.Design: After a 2-wk provided-food run-in period of consuming a Western-style diet, 49 men and 32 postmenopausal women [age range: 40-65 y, body mass index (in kg/m2) <35] were assigned to consume 1 of 2 provided-food weight-maintenance diets for 6 wk.Results: Compared with the RG group, the WG group had increased plasma total alkyresorcinols (a measure of WG intake) (P < 0.0001), stool weight (P < 0.0001), stool frequency (P = 0.02), and short-chain fatty acid (SCFA) producer Lachnospira [false-discovery rate (FDR)-corrected P = 0.25] but decreased pro-inflammatory Enterobacteriaceae (FDR-corrected P = 0.25). Changes in stool acetate (P = 0.02) and total SCFAs (P = 0.05) were higher in the WG group than in the RG group. A positive association was shown between Lachnospira and acetate (FDR-corrected P = 0.002) or butyrate (FDR-corrected P = 0.005). We also showed that there was a higher percentage of terminal effector memory T cells (P = 0.03) and LPS-stimulated ex vivo production of tumor necrosis factor-α (P = 0.04) in the WG group than in the RG group, which were positively associated with plasma alkylresorcinol concentrations.Conclusion: The short-term consumption of WGs in a weight-maintenance diet increases stool weight and frequency and has modest positive effects on gut microbiota, SCFAs, effector memory T cells, and the acute innate immune response and no effect on other markers of cell-mediated immunity or systemic and gut inflammation. This trial was registered at clinicaltrials.gov as NCT01902394.

Vitamin D status, dietary intake, and bone turnover in female Soldiers during military training: a longitudinal study

BackgroundVitamin D is an essential nutrient for maintaining bone health, to include protecting against stress fracture during periods of rapid bone turnover. The objective of this longitudinal, observational study was to assess vitamin D status, biomarkers of bone turnover, and vitamin D and calcium intake in female Soldiers (n = 91) during US Army basic combat training (BCT).MethodsAnthropometric, biological and dietary intake data were collected at wk 0, 3, 6, and 9 of the 10 wk BCT course. Mixed models repeated measures ANOVAs were used to assess main effects of time, race, and time-by-race interactions.ResultsWhite volunteers experienced a decrease in serum 25(OH)D levels, whereas non-white volunteers experienced an increase during BCT. However, serum 25(OH)D levels were lower in non-whites than whites at all timepoints (P-interaction < 0.05). Group mean PTH levels increased (P < 0.05) during the first 3 wk of training, remained elevated for the duration of BCT, and were higher in non-whites compared to whites (P-race < 0.05). Biomarkers of both bone formation (bone alkaline phosphatase and procollagen I N-terminal peptide) and resorption (tartrate-resistant acid phosphatase and C-terminal telopeptide) increased (P < 0.05) during BCT, indicating increased bone turnover. Estimated daily intakes of vitamin D and calcium were below recommended levels (15 μg and 1000 mg/day, respectively), both before (group mean ± SEM; 3.9 μg/d ± 0.4 and 887 mg/d ± 67) and during BCT (4.1 μg/d ± 0.3 and 882 mg/d ± 51).ConclusionsThese findings demonstrate that female Soldiers experience dynamic changes in vitamin D status coupled with increased bone turnover and potentially inadequate vitamin D and calcium intake during military training.

Changes in intestinal microbiota composition and metabolism coincide with increased intestinal permeability in young adults under prolonged physiological stress

The magnitude, temporal dynamics, and physiological effects of intestinal microbiome responses to physiological stress are poorly characterized. This study used a systems biology approach and a multiple-stressor military training environment to determine the effects of physiological stress on intestinal microbiota composition and metabolic activity, as well as intestinal permeability (IP). Soldiers (n = 73) were provided three rations per day with or without protein- or carbohydrate-based supplements during a 4-day cross-country ski-march (STRESS). IP was measured before and during STRESS. Blood and stool samples were collected before and after STRESS to measure inflammation, stool microbiota, and stool and plasma global metabolite profiles. IP increased 62 ± 57% (mean ± SD, P < 0.001) during STRESS independent of diet group and was associated with increased inflammation. Intestinal microbiota responses were characterized by increased α-diversity and changes in the relative abundance of >50% of identified genera, including increased abundance of less dominant taxa at the expense of more dominant taxa such as Bacteroides Changes in intestinal microbiota composition were linked to 23% of metabolites that were significantly altered in stool after STRESS. Together, pre-STRESS Actinobacteria relative abundance and changes in serum IL-6 and stool cysteine concentrations accounted for 84% of the variability in the change in IP. Findings demonstrate that a multiple-stressor military training environment induced increases in IP that were associated with alterations in markers of inflammation and with intestinal microbiota composition and metabolism. Associations between IP, the pre-STRESS microbiota, and microbiota metabolites suggest that targeting the intestinal microbiota could provide novel strategies for preserving IP during physiological stress.NEW & NOTEWORTHY Military training, a unique model for studying temporal dynamics of intestinal barrier and intestinal microbiota responses to stress, resulted in increased intestinal permeability concomitant with changes in intestinal microbiota composition and metabolism. Prestress intestinal microbiota composition and changes in fecal concentrations of metabolites linked to the microbiota were associated with increased intestinal permeability. Findings suggest that targeting the intestinal microbiota could provide novel strategies for mitigating increases in intestinal permeability during stress.