Association between hip muscle strength/function and hip cartilage defects in sub-elite football players with hip/groin pain.

OBJECTIVE: To explore associations between hip muscle strength and cartilage defects (presence and severity) on magnetic resonance imaging (MRI) in young adults with hip/groin pain participating in sub-elite football. DESIGN: Sub-elite football players with hip/groin pain (>6 months) completed assessments of isometric hip strength and functional task performance. Hip cartilage defects were assessed using the Scoring Hip Osteoarthritis with MRI tool. This exploratory, cross-sectional study used logistic and negative binomial models to assess the relationships between hip muscle strength or functional task performance and hip cartilage defects, controlling for body mass index, age, testing site and cam morphology, incorporating sex-specific interaction terms. RESULTS: One hundred and eighty-two (37 women) sub-elite (soccer or Australian football) players with hip/groin pain (age 26 ± 7 years) were included. Greater hip extension strength was associated with higher cartilage total score (adjusted incidence rate ratio [aIRR] 1.01, 95%CI: 1.0 to 1.02, p = 0.013) and superolateral cartilage score (adjusted odds ratio (aOR) 1.03, 95% confidence interval (CI): 1.01 to 1.06, p < 0.01). In female sub-elite football players, greater hip external rotation strength was associated with lateral cartilage defects (aOR 1.61, 95%CI: 1.05 to 2.48, p = 0.03) and higher cartilage total score (aIRR 1.25, 95%CI: 1.01 to 1.66, p = 0.042). A one-repetition increase in one-leg rise performance was related to lower odds of superomedial cartilage defects (aOR 0.96, 95%CI: 0.94 to 0.99, p < 0.01). CONCLUSIONS: Overall, there were few associations between peak isometric hip muscle strength and overall hip cartilage defects. It is possible that other factors may have relevance in sub-elite football players. Additional studies are needed to support or refute our findings that higher one leg rise performance was associated with reduced superomedial cartilage defect severity and greater hip extension strength was related to higher cartilage defect severity scores.

Is running good or bad for your knees? A systematic review and meta-analysis of cartilage morphology and composition changes in the tibiofemoral and patellofemoral joints.

BACKGROUND: The general health benefits of running are well-established, yet concern exists regarding the development and progression of osteoarthritis. AIM: To systematically review the immediate (within 20 min) and delayed (20 min-48 h) effect of running on hip and knee cartilage, as assessed using magnetic resonance imaging (MRI). METHOD: Studies using MRI to measure change in hip or knee cartilage within 48 h pre- and post-running were identified. Risk of bias was assessed using a modified Newcastle-Ottawa Scale. Percentage change in cartilage outcomes were estimated using random-effects meta-analysis. Certainty of evidence was evaluated with the Grading of Recommendations Assessment, Development and Evaluation tool. RESULTS: Twenty-four studies were included, evaluating 446 knees only. One third of studies were low risk of bias. Knee cartilage thickness and volume decreased immediately after running, with declines ranging from 3.3% (95% confidence interval [CI]: 2.6%, 4.1%) for weight-bearing femoral cartilage volume to 4.9% (95% CI: 4.43.6%, 6.2%) for patellar cartilage volume. T1ρ and T2 relaxation times were also reduced immediately after running, with the largest decline being 13.1% (95% CI: -14.4%, -11.7%) in femoral trochlear cartilage. Tibiofemoral cartilage T2 relaxation times recovered to baseline levels within 91 min. Existing cartilage defects were unchanged within 48 h post-run. CONCLUSIONS: There is very low certainty evidence that running immediately decreases the thickness, volume, and relaxation times of patellofemoral and tibiofemoral cartilage. Hip cartilage changes are unknown, but knee changes are small and appear transient suggesting that a single bout of running is not detrimental to knee cartilage.

Prenatal Maternal Depressive Symptoms Predict Early Infant Health Concerns.

INTRODUCTION: Recent research suggests that health disparities among low-SES and ethnic minority populations may originate from prenatal and early life exposures. Postpartum maternal depressive symptoms have been linked to poorer infant physical health, yet prenatal depressive symptoms not been thoroughly examined in relation to infant health. METHODS: In a prospective study of low-income Mexican American mothers and their infants, women (N = 322, median age 27.23, IQR = 22.01-32.54) completed surveys during pregnancy (median gestation 39.50, IQR = 38.71-40.14 weeks) and 12 weeks after birth. We investigated (1) if prenatal depressive symptoms predicted infant physical health concerns at 12 weeks of age, (2) whether these associations occurred above and beyond concurrent depressive symptoms, and (3) if birth weight, gestational age, and breastfeeding were mediators of prenatal depression predicting subsequent infant health. RESULTS: Higher prenatal depressive symptoms were associated with more infant physical health concerns at 12 weeks (p < .001), after accounting for 12-week maternal depressive symptoms, breastfeeding, gestational age, and birth weight. Twelve-week maternal depressive symptoms were concurrently associated with more infant health concerns (p < .01). Birth weight, gestational age, and breastfeeding were not associated with maternal depression or infant health concerns. DISCUSSION: Results establish a link between prenatal depressive symptoms and an elevated risk of poor health evident shortly after birth. These findings underscore the importance of the prenatal period as a possible sensitive period for infants' health, and the need for effective interventions for depression during pregnancy to mitigate potentially teratogenic effects on the developing fetus and reduce risks for later health concerns.

International patterns and trends in ovarian cancer incidence, overall and by histologic subtype.

Internationally, ovarian cancer is the 7th leading cancer diagnosis and 8th leading cause of cancer mortality among women. Ovarian cancer incidence varies by region, particularly when comparing high vs. low-income countries. Temporal changes in reproductive factors coupled with shifts in diagnostic criteria may have influenced incidence trends of ovarian cancer and relative rates by histologic subtype. Accordingly, we evaluated trends in ovarian cancer incidence overall (1973-1977 to 2003-2007) and by histologic subtype (1988-1992 to 2003-2007) using volumes IV-IX of the Cancer Incidence in Five Continents database (CI5plus) and CI5X (volume X) database. Annual percent changes were calculated for ovarian cancer incidence trends, and rates of histologic subtypes for individual countries were compared to overall international incidence. Ovarian cancer incidence rates were stable across regions, although there were notable increases in Eastern/Southern Europe (e.g., Poland: Annual Percent Change (APC) 1.6%, p = 0.02) and Asia (e.g., Japan: APC 1.7%, p = 0.01) and decreases in Northern Europe (e.g., Denmark: APC -0.7%, p = 0.01) and North America (e.g., US Whites: APC -0.9%, p < 0.01). Relative proportions of histologic subtypes were similar across countries, except for Asian nations, where clear cell and endometrioid carcinomas comprised a higher proportion of the rate and serous carcinomas comprised a lower proportion of the rate than the worldwide distribution. Geographic variation in temporal trends of ovarian cancer incidence and differences in the distribution of histologic subtype may be partially explained by reproductive and genetic factors. Thus, histology-specific ovarian cancer should continue to be monitored to further understand the etiology of this neoplasm.

Mice lacking tissue non-specific alkaline phosphatase die from seizures due to defective metabolism of vitamin B-6.

In humans, deficiency of the tissue non-specific alkaline phosphatase (TNAP) gene is associated with defective skeletal mineralization. In contrast, mice lacking TNAP generated by homologous recombination using embryonic stem (ES) cells have normal skeletal development. However, at approximately two weeks after birth, homozygous mutant mice develop seizures which are subsequently fatal. Defective metabolism of pyridoxal 5'-phosphate (PLP), characterized by elevated serum PLP levels, results in reduced levels of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) in the brain. The mutant seizure phenotype can be rescued by the administration of pyridoxal and a semi-solid diet. Rescued animals subsequently develop defective dentition. This study reveals essential physiological functions of TNAP in the mouse.

Effects of 21 days of bed rest, with or without artificial gravity, on nutritional status of humans.

Spaceflight and bed rest models of microgravity have profound effects on physiological systems, including the cardiovascular, musculoskeletal, and immune systems. These effects can be exacerbated by suboptimal nutrient status, and therefore it is critical to monitor nutritional status when evaluating countermeasures to mitigate negative effects of spaceflight. As part of a larger study to investigate the usefulness of artificial gravity as a countermeasure for musculoskeletal and cardiovascular deficits during bed rest, we tested the hypothesis that artificial gravity would have an effect on some aspects of nutritional status. Dietary intake was recorded daily before, during, and after 21 days of bed rest with artificial gravity (n = 8) or bed rest alone (n = 7). We examined body composition, hematology, general blood chemistry, markers of oxidative damage, and blood levels of selected vitamins and minerals before, during, and after the bed rest period. Several indicators of vitamin status changed in response to diet changes: serum alpha- and gamma-tocopherol and urinary 4-pyridoxic acid decreased (P < 0.001) and plasma beta-carotene increased (P < 0.001) in both groups during bed rest compared with before bed rest. A decrease in hematocrit (P < 0.001) after bed rest was accompanied by a decrease in transferrin (P < 0.001), but transferrin receptors were not changed. These data provide evidence that artificial gravity itself does not negatively affect nutritional status during bed rest. Likewise, artificial gravity has no protective effect on nutritional status during bed rest.

Cardiovascular disease-risk factors in middle-aged osteopaenic women treated with calcium alone or combined to three nutrients essential to artery and bone collagen.

BACKGROUND: Recent research suggests that cardiovascular disease (CVD) and bone loss are functionally interwoven. This study examined the concomitant effects of a nutritional treatment of osteopaenia on CVD-risk factors. METHODS: A 1-year placebo-controlled trial was conducted on middle-aged women with normal (group A) or low (groups B and C) bone mineral density. Subjects (n = 20 per group) took daily either a placebo, calcium carbonate alone or combined to a vitamin (C and B(6))-proline capsule, respectively. Urinary pyridoxic acid (used to assess treatment compliance), plasma homocysteine, serum lipids and lipoproteins were measured before and after nutritional intervention. RESULTS: Groups were comparable at baseline in most parameters of interest. No changes occurred in groups A and B. The 4%, 7% and 25% reductions of total cholesterol, LDL and triglycerides, and 14% elevation of HDL were all significant in group C. A trend toward reduction was observed for homocysteine in this group. CONCLUSIONS: Vitamins C (500 mg) and B(6) (75 mg) combined with proline had consistent beneficial effects on CVD-risk factors, whereas calcium alone did not. This study also underlined the importance of considering vitamin B(6) status as a potential CVD risk factor.

Associations between circulating sex steroid hormones and leukocyte telomere length in men in the National Health and Nutrition Examination Survey.

Preliminary evidence suggests that sex steroid hormones, such as danazol (a synthetic sex steroid hormone), may be involved in enhancing telomerase activity. Elucidating underlying mechanisms of telomerase activity may further therapeutic options for individuals with telomeropathies and potentially avert certain age-related conditions. Therefore, we conducted a cross-sectional study to investigate the relationship between circulating sex steroid hormones and SHBG with leukocyte telomere length among 499 males in NHANES (1999-2002 surveys). Sample-weighted linear regression analyses were conducted to assess age-adjusted and multivariable-adjusted estimates of associations. Estimates were rescaled to represent telomere length change in base pairs per half the value of the interquartile range of the independent variable. Estradiol and free estradiol were significantly inversely associated with leukocyte telomere length (ßcontinuous per §IQR  = -61, p = 0.04; free estradiol ßcontinuous per §IQR  = -67, p = 0.03). Testosterone, free testosterone, androstanediol glucuronide, and SHBG were not associated with leukocyte telomere length. The inverse association seen in this study indicates that a danazol-induced hypoestrogenic state could partly underlie the previously observed association between danazol therapy and increased leukocyte telomere length.

Markedly increased circulating pyridoxal-5'-phosphate levels in hypophosphatasia. Alkaline phosphatase acts in vitamin B6 metabolism.

Markedly increased circulating concentrations of pyridoxal-5'-phosphate (PLP) were found in each of 14 patients representing all clinical forms of hypophosphatasia, an inborn error characterized by deficient activity of the tissue nonspecific (bone/liver/kidney) isoenzyme of alkaline phosphatase (AP). The mean PLP concentration in plasma was 1174 nM (range, 214-3839 nM) in the patients and 57 +/- 26 nM (mean +/- SD) in 38 control subjects. In four affected children, urinary excretion of the PLP degradation product, 4-pyridoxic acid, was unremarkable during consumption of normal quantities of dietary vitamin B6. Our findings identify increased circulating PLP concentration as a marker for hypophosphatasia and provide further evidence that tissue nonspecific AP acts in vitamin B6 metabolism. Tissue nonspecific AP appears to function as an ectoenzyme to regulate extracellular but not intracellular levels of PLP substrate. Performing assays of circulating PLP concentration alone to assess vitamin B6 nutrition may be misleading in disorders associated with altered AP activity.

Perinatal hypophosphatasia: tissue levels of vitamin B6 are unremarkable despite markedly increased circulating concentrations of pyridoxal-5'-phosphate. Evidence for an ectoenzyme role for tissue-nonspecific alkaline phosphatase.

"Perinatal" hypophosphatasia is the most severe form of this inborn error of metabolism, which is characterized by deficient activity of the tissue-nonspecific (liver/bone/kidney) isoenzyme of alkaline phosphatase (ALP) (TNSALP). We report that autopsy tissue from three affected subjects, which was profoundly low in ALP activity, had essentially unremarkable levels of pyridoxal-5'-phosphate (PLP), pyridoxal, and total vitamin B6 content despite markedly elevated plasma PLP levels (5,800, 14,500, and 98,500 nM; adult norm, 5-109 nM). Our findings help to explain the general absence of symptoms of vitamin B6 excess or deficiency in hypophosphatasia, and provide evidence that TNSALP acts as an ectoenzyme to regulate extracellular rather than intracellular concentrations of PLP (the cofactor form of vitamin B6) and perhaps other phosphate compounds.

Alkaline phosphatase: placental and tissue-nonspecific isoenzymes hydrolyze phosphoethanolamine, inorganic pyrophosphate, and pyridoxal 5'-phosphate. Substrate accumulation in carriers of hypophosphatasia corrects during pregnancy.

Hypophosphatasia features selective deficiency of activity of the tissue-nonspecific (liver/bone/kidney) alkaline phosphatase (ALP) isoenzyme (TNSALP); placental and intestinal ALP isoenzyme (PALP and IALP, respectively) activity is not reduced. Three phosphocompounds (phosphoethanolamine [PEA], inorganic pyrophosphate [PPi], and pyridoxal 5'-phosphate [PLP]) accumulate endogenously and appear, therefore, to be natural substrates for TNSALP. Carriers for hypophosphatasia may have decreased serum ALP activity and elevated substrate levels. To test whether human PALP and TNSALP are physiologically active toward the same substrates, we studied PEA, PPi, and PLP levels during and after pregnancy in three women who are carriers for hypophosphatasia. Hypophosphatasemia corrected during the third trimester because of PALP in maternal blood. Blood or urine concentrations of PEA, PPi, and PLP diminished substantially during that time. After childbirth, maternal circulating levels of PALP decreased, and PEA, PPi, and PLP levels abruptly increased. In serum, unremarkable concentrations of IALP and low levels of TNSALP did not change during the study period. We conclude that PALP, like TNSALP, is physiologically active toward PEA, PPi, and PLP in humans. We speculate from molecular/crystallographic information, indicating significant similarity of structure of the substrate-binding site of ALPs throughout nature, that all ALP isoenzymes recognize these same three phosphocompound substrates.

Patient-provider communication in nephrology care for adolescents and young adults.

OBJECTIVE: To compare the relative quantity of talk between providers, caregivers, and adolescents and young adults (AYAs) with chronic kidney disease (CKD) and how communication differs by age. METHODS: During nephrology clinic visits, conversations between AYAs with CKD (N=99, ages 11-20, median=15), their caregivers, and providers (N=19) were audiotaped and coded using the Roter Interaction Analysis System. Linear mixed models tested AYA age differences in talk frequency by AYAs, caregivers, and providers. Post-hoc analyses tested differences in talk using AYA age groups. RESULTS: During clinic visits, providers spoke the most (63.7%), and caregivers spoke more (22.6%) than AYAs (13.7%). Overall talk differed by AYA age in AYAs (p<0.001) and caregivers (p<0.05), but not providers. Higher AYA age was associated with more AYA talk (biomedical information-giving, partnering, rapport-oriented) and less caregiver biomedical information-giving (ps<0.001-0.05). In post-hoc analyses, young adults talked more than adolescents; caregiver talk decreased in the middle-adolescent group. CONCLUSIONS: Increases in AYA talk occur primarily in young adulthood, whereas caregiver talk decreases in middle adolescence. This may indicate an appropriate developmental shift but raises concerns about conversational gaps during middle-adolescence. PRACTICE IMPLICATIONS: During transition-oriented treatment planning, providers should engage both AYAs and caregivers to avoid potential gaps in communication.

Cementum and dentin in hypophosphatasia.

Hypophosphatasia (HPP) often leads to premature loss of deciduous teeth, due to disturbed cementum formation. We addressed the question to what extent cementum and dentin are similarly affected. To this end, we compared teeth from children with HPP with those from matched controls and analyzed them microscopically and chemically. It was observed that both acellular and cellular cementum formation was affected. For dentin, however, no differences in mineral content were recorded. To explain the dissimilar effects on cementum and dentin in HPP, we assessed pyrophosphate (an inhibitor of mineralization) and the expression/activity of enzymes related to pyrophosphate metabolism in both the periodontal ligament and the pulp of normal teeth. Expression of nucleotide pyrophosphatase phosphodiesterase 1 (NPP1) in pulp proved to be significantly lower than in the periodontal ligament. Also, the activity of NPP1 was less in pulp, as was the concentration of pyrophosphate. Our findings suggest that mineralization of dentin is less likely to be under the influence of the inhibitory action of pyrophosphate than mineralization of cementum.

Elevation of plasma homocysteine in natural menopause can not be explained by a lack of vitamin coenzyme availability: relevance to the risk of cardiovascular disease.

UNLABELLED: The risk of cardio vascular disease (CVD) doubles after menopause. Plasma homocysteine (hCy) is a risk factor which is influenced by vitamins B12,B6 and folate. The present study was conducted to examine the relationship of plasma hCy to the three vitamins and other contributing variables in early natural menopause. METHODS: Participants were healthy, non smoking Caucasian women 3 to 5 years postmenopausal (n = 26) or premenopausal between 30 and 45 y(n = 30). Anthropometric data, dietary records and plasma concentrations of hCy, vitamin B6, vitamin B12 and folate were obtained. RESULTS: The nutritional status of vitamins B6, B12 and folate as measured by dietary intake and blood concentrations was adequate in both groups. Mean fasting plasma total (t) hCy concentration of postmenopausal group was 2-fold higher than the value found for control group (P < 0.0001) without oral methionine loading. The difference between the two groups remained highly significant after adjustment for confounding variables by multivariate analysis, suggesting that the effect of estrogen deficiency was direct. CONCLUSION: In addition to the loss of the protective effects of estrogen on their cardiovascular physiology and lipid metabolism, postmenopausal women are exposed to higher plasma hCy concentrations and deleterious cardiovascular effects. The exact mechanism is not known but does not seem to be related to coenzyme deficiency.

Alkaline phosphatase knock-out mice recapitulate the metabolic and skeletal defects of infantile hypophosphatasia.

Hypophosphatasia is an inborn error of metabolism characterized by deficient activity of the tissue-nonspecific isoenzyme of alkaline phosphatase (TNSALP) and skeletal disease due to impaired mineralization of cartilage and bone matrix. We investigated two independently generated TNSALP gene knock-out mouse strains as potential models for hypophosphatasia. Homozygous mice (-/-) had < 1% of wild-type plasma TNSALP activity; heterozygotes had the predicted mean of approximately 50%. Phosphoethanolamine, inorganic pyrophosphate, and pyridoxal 5'-phosphate are putative natural substrates for TNSALP and all were increased endogenously in the knock-out mice. Skeletal disease first appeared radiographically at approximately 10 days of age and featured worsening rachitic changes, osteopenia, and fracture. Histologic studies revealed developmental arrest of chondrocyte differentiation in epiphyses and in growth plates with diminished or absent hypertrophic zones. Progressive osteoidosis from defective skeletal matrix mineralization was noted but not associated with features of secondary hyperparathyroidism. Plasma and urine calcium and phosphate levels were unremarkable. Our findings demonstrate that TNSALP knock-out mice are a good model for the infantile form of hypophosphatasia and provide compelling evidence for an important role for TNSALP in postnatal development and mineralization of the murine skeleton.

Alkaline phosphatase (EC 3.1.3.1) in serum is inhibited by physiological concentrations of inorganic phosphate.

Natural and artificial manipulation of tissue nonspecific alkaline phosphatase activity indicates that pyrophosphate, phosphoethanolamine, and pyridoxal 5'-phosphate are among the natural substrates for this enzyme. Although inorganic phosphate has been recognized as a competitive inhibitor of this enzyme for many years, the influence of phosphate on alkaline phosphatase activity in serum under physiological conditions has not been previously reported. We examined the kinetics of tissue nonspecific alkaline phosphatase from bovine kidney and sera from 49 patients with a wide range of endogenous phosphate concentrations using pyridoxine 5'-phosphate as a substrate at pH 7.4. For the bovine kidney enzyme, the Km was 0.42 +/- 0.04 micromol/L, and the Ki for phosphate was 2.4 +/- 0.2 micromol/L. Analysis of the kinetics using pyridoxine 5'-phosphate in undiluted serum from 10 subjects with phosphorus ranging from 0.5-2.1 mmol/L and alkaline phosphatase activity ranging from 41-165 nmol/min x mL gave estimates for the Km of 56 +/- 11 micromol/L and for the Ki of 540 +/- 82 micromol/L for phosphate. This indicates that under physiological conditions alkaline phosphatase activity toward pyridoxine 5'-phosphate is reduced approximately 50% by the normal phosphate concentration and that it will increase or decrease significantly in response to changes in phosphate concentration within the ranges observed clinically.

Effect of megavitamin treatment on mental performance and plasma vitamin B6 concentrations in mentally retarded young adults.

Other workers have reported preliminary results suggesting that vitamin and mineral supplements might improve the mental performance of mentally retarded children. The current study examined the effect of 20 wk of the suggested supplement on Stanford Binet scores in mentally retarded adults with nonspecific diagnoses, Down's syndrome, and subjects receiving anticonvulsant medication. No improvement in Stanford Binet scores was observed. However, serum pyridoxal phosphate concentrations were significantly (p less than 0.05) increased in subjects with Down's syndrome receiving the supplement compared with subjects with nonspecific diagnoses receiving the same treatment thus providing further evidence of abnormal vitamin B6 metabolism in Down's syndrome.

Human vitamin B-6 pools estimated through muscle biopsies.

Previous estimates of total vitamin B-6 pools in humans based on extrapolations from tracer studies yielded values of 107-190 mumol when the tracer was administered orally and 345-725 mumol when the tracer was administered intravenously. To obtain a more direct estimate of vitamin B-6 pools, muscle biopsies from five female and seven male adults were analyzed by cation-exchange chromatography. Total muscle mass was estimated from creatinine excretion and the assumption that muscle is 40% of the body weight. The total muscle vitamin B-6 pool was estimated to be 917 +/- 319 mumol in the females and 850 +/- 216 mumol in the males. Because muscle accounts for approximately 80% of the vitamin B-6 in the body, the total body pool of vitamin B-6 in adult humans is probably approximately 1000 mumol.

Response of vitamin B-6 content of muscle to changes in vitamin B-6 intake in men.

Previous reports indicated that in growing rats the vitamin B-6 pool in muscle was relatively stable during deficiency but increased in response to increased vitamin B-6 intake. To determine whether human muscle would show a similar response 10 college-aged males received a low vitamin B-6 diet (1.76 mumol/d) for 6 wk followed by 6 wk on a self-selected diet supplemented with 0.98 mmol pyridoxine HCl/d. During depletion, excretion of pyridoxic acid rapidly adjusted to approximate the intake. Plasma pyridoxal phosphate concentrations at the end of the baseline, depletion, and supplementation periods were 81 +/- 51, 9 +/- 3, and 455 +/- 129 nmol/L, respectively, whereas muscle concentrations were 21 +/- 9, 20 +/- 4, and 25 +/- 7 nmol/g, respectively and total vitamin B-6 in muscle was 28 +/- 10, 27 +/- 4, and 35 +/- 10 nmol/g, respectively. These data provide further confirmation that the vitamin B-6 pools in skeletal muscle are resistant to depletion. They also demonstrate that in humans with constant body weight, vitamin B-6 supplementation is not associated with marked increases in vitamin B-6 in muscle.

Pyridoxic acid excretion during low vitamin B-6 intake, total fasting, and bed rest.

Vitamin B-6 metabolism in 10 volunteers during 21 d of total fasting was compared with results from 10 men consuming a diet low only in vitamin B-6 (1.76 mumol/d) and with men consuming a normal diet during bed rest. At the end of the fast mean plasma concentrations of vitamin B-6 metabolites and urinary excretion of 4-pyridoxic acid tended to be higher in the fasting subjects than in the low-vitamin B-6 group. The fasting subjects lost approximately 10% of their total vitamin B-6 pool and approximately 13% of their body weight. The low-vitamin B-6 group lost only approximately 4% of their vitamin B-6 pool. Compared with baseline, urinary excretion of pyridoxic acid was significantly increased during 17 wk of bed rest. There was no increase in pyridoxic acid excretion during a second 15-d bed rest study. These data suggest the possibility of complex interactions between diet and muscle metabolism that may influence indexes that are frequently used to assess vitamin B-6 status.