Randomized, controlled trial to assess the safety and efficacy of odanacatib in the treatment of men with osteoporosis.

Odanacatib (ODN) was investigated as an osteoporosis treatment in 292 men. Compared with placebo, odanacatib improved bone mineral density and led to sustained bone resorption decreases while producing relatively little bone formation reduction that leveled off with time. However, increased risk of stroke in another study stopped further odanacatib development. INTRODUCTION: ODN, a selective oral cathepsin K inhibitor, was in development for osteoporosis treatment. This phase 3, double-blind, randomized, placebo-controlled, 24-month study investigated ODN safety and efficacy in men with osteoporosis. METHODS: Men with idiopathic osteoporosis or osteoporosis due to hypogonadism and a lumbar spine or hip (total hip [TH], femoral neck [FN], or trochanter) bone mineral density (BMD) T-score of ≤ - 2.5 to ≥ - 4.0 without prior vertebral fracture or ≤ - 1.5 to ≥ - 4.0 with one prior vertebral fracture were randomized (1:1) to once-weekly ODN 50 mg or placebo. All received 5600 IU vitamin D3 weekly and calcium supplementation as needed (≥ 1200 mg daily). The primary efficacy outcome was changed from baseline in lumbar spine BMD versus placebo. RESULTS: Overall, 292 men, mean age 68.8 years, were randomly assigned to ODN or placebo. Versus placebo, ODN increased BMD from baseline at the lumbar spine, TH, FN, and trochanter by 5.6%, 2.0%, 1.7%, and 2.1%, respectively (all p < 0.01), and decreased uNTx/Cr (68%, p < 0.001), sCTx (77%, p < 0.001), sP1NP (16%, p = 0.001), and sBSAP (8%, p = 0.019). The between-group bone formation marker decrease peaked at 3 months, then returned toward baseline. The safety profile, including cardiovascular events, was similar between groups. CONCLUSION: Though a promising osteoporosis therapy for men, ODN development was discontinued due to increased risk of stroke in the LOFT phase 3 trial. TRIAL REGISTRATION: Clinicaltrials.gov NCT01120600 (registered May 11, 2010).

Consensus statement from 2nd International Conference on Controversies in Vitamin D.

The 2nd International Conference on Controversies in Vitamin D was held in Monteriggioni (Siena), Italy, September 11-14, 2018. The aim of this meeting was to address ongoing controversies and timely topics in vitamin D research, to review available data related to these topics and controversies, to promote discussion to help resolve lingering issues and ultimately to suggest a research agenda to clarify areas of uncertainty. Several issues from the first conference, held in 2017, were revisited, such as assays used to determine serum 25-hydroxyvitamin D [25(OH)D] concentration, which remains a critical and controversial issue for defining vitamin D status. Definitions of vitamin D nutritional status (i.e. sufficiency, insufficiency and deficiency) were also revisited. New areas were reviewed, including vitamin D threshold values and how they should be defined in the context of specific diseases, sources of vitamin D and risk factors associated with vitamin D deficiency. Non-skeletal aspects related to vitamin D were also discussed, including the reproductive system, neurology, chronic kidney disease and falls. The therapeutic role of vitamin D and findings from recent clinical trials were also addressed. The topics were considered by 3 focus groups and divided into three main areas: 1) "Laboratory": assays and threshold values to define vitamin D status; 2) "Clinical": sources of vitamin D and risk factors and role of vitamin D in non-skeletal disease and 3) "Therapeutics": controversial issues on observational studies and recent randomized controlled trials. In this report, we present a summary of our findings.

Nutrition and physical activity in the prevention and treatment of sarcopenia: systematic review.

This systematic review summarizes the effect of combined exercise and nutrition intervention on muscle mass and muscle function. A total of 37 RCTs were identified. Results indicate that physical exercise has a positive impact on muscle mass and muscle function in subjects aged 65 years and older. However, any interactive effect of dietary supplementation appears to be limited. INTRODUCTION: In 2013, Denison et al. conducted a systematic review including 17 randomized controlled trials (RCTs) to explore the effect of combined exercise and nutrition intervention to improve muscle mass, muscle strength, or physical performance in older people. They concluded that further studies were needed to provide evidence upon which public health and clinical recommendations could be based. The purpose of the present work was to update the prior systematic review and include studies published up to October 2015. METHODS: Using the electronic databases MEDLINE and EMBASE, we identified RCTs which assessed the combined effect of exercise training and nutritional supplementation on muscle strength, muscle mass, or physical performance in subjects aged 60 years and over. Study selection and data extraction were performed by two independent reviewers. RESULTS: The search strategy identified 21 additional RCTs giving a total of 37 RCTs. Studies were heterogeneous in terms of protocols for physical exercise and dietary supplementation (proteins, essential amino acids, creatine, ß-hydroxy-ß-methylbuthyrate, vitamin D, multi-nutrients, or other). In 79% of the studies (27/34 RCTs), muscle mass increased with exercise but an additional effect of nutrition was only found in 8 RCTs (23.5%). Muscle strength increased in 82.8% of the studies (29/35 RCTs) following exercise intervention, and dietary supplementation showed additional benefits in only a small number of studies (8/35 RCTS, 22.8%). Finally, the majority of studies showed an increase of physical performance following exercise intervention (26/28 RCTs, 92.8%) but interaction with nutrition supplementation was only found in 14.3% of these studies (4/28 RCTs). CONCLUSION: Physical exercise has a positive impact on muscle mass and muscle function in healthy subjects aged 60 years and older. The biggest effect of exercise intervention, of any type, has been seen on physical performance (gait speed, chair rising test, balance, SPPB test, etc.). We observed huge variations in regard to the dietary supplementation protocols. Based on the included studies, mainly performed on well-nourished subjects, the interactive effect of dietary supplementation on muscle function appears limited.

Developing vitamin D dietary guidelines and the lack of 25-hydroxyvitamin D assay standardization: The ever-present past.

Unstandardized laboratory measurement of 25-hydroxyvitamin D (25(OH)D) confounds efforts to develop clinical and public health vitamin D guidelines. The Vitamin D Standardization Program (VDSP), an international collaborative effort, was founded in 2010 to correct this problem. Nearly all published vitamin D research is based on unstandardized laboratory 25(OH)D measurements. While it is impossible to standardize all old data, it may be possible to identify a small subset of prior studies critical to guidelines development. Once identified it may be possible to calibrate their 25(OH)D values to the NIST and Ghent University reference measurement procedures using VDSP methods thereby permitting future guidelines to be based on standardized results. We simulated the calibration of a small set of ten clinical trials of vitamin D supplementation on achieved 25(OH)D under minimal sun exposure. These studies were selected because they played a prominent role in setting the 2010 vitamin D dietary reference intakes (DRI). Using random-effects meta-regression analysis, Vitamin D External Quality Assessment (DEQAS) data on assay bias was used to simulate the potential bias due to the lack of assay standardization by calibrating the achieved 25(OH)D levels from those 10 studies to: (1) the largest negative, and (2) the largest positive bias from the DEQAS all laboratory trimmed mean (ALTM) for the appropriate assay and year of analysis. For a usual vitamin D intake of 600IU/day the difference in mean achieved 25(OH)D values for those two options was 20nmol/L. However, without re-calibration of 25(OH)D values it is impossible to know the degree to which any of the current guidelines may have been biased. This approach may help stimulate the search for and standardization of that small subset of key studies and, in the cases where standardization is impossible, to identify areas of urgently needed vitamin D research.

Trabecular bone score (TBS) as a new complementary approach for osteoporosis evaluation in clinical practice.

Trabecular bone score (TBS) is a recently-developed analytical tool that performs novel grey-level texture measurements on lumbar spine dual X-ray absorptiometry (DXA) images, and thereby captures information relating to trabecular microarchitecture. In order for TBS to usefully add to bone mineral density (BMD) and clinical risk factors in osteoporosis risk stratification, it must be independently associated with fracture risk, readily obtainable, and ideally, present a risk which is amenable to osteoporosis treatment. This paper summarizes a review of the scientific literature performed by a Working Group of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis. Low TBS is consistently associated with an increase in both prevalent and incident fractures that is partly independent of both clinical risk factors and areal BMD (aBMD) at the lumbar spine and proximal femur. More recently, TBS has been shown to have predictive value for fracture independent of fracture probabilities using the FRAX® algorithm. Although TBS changes with osteoporosis treatment, the magnitude is less than that of aBMD of the spine, and it is not clear how change in TBS relates to fracture risk reduction. TBS may also have a role in the assessment of fracture risk in some causes of secondary osteoporosis (e.g., diabetes, hyperparathyroidism and glucocorticoid-induced osteoporosis). In conclusion, there is a role for TBS in fracture risk assessment in combination with both aBMD and FRAX.

Can vitamin D metabolite measurements facilitate a "treat-to-target" paradigm to guide vitamin D supplementation?

UNLABELLED: Substantial variability exists in the serum 25(OH)D increase observed in response to vitamin D supplementation. Measurement of circulating cholecalciferol and 24,25(OH)2D, as indicators of vitamin D absorption and degradation, respectively, account for approximately half of the variation in serum 25(OH)D observed following supplementation. INTRODUCTION: Vitamin D supplementation produces a variable response in serum 25(OH)D. This variability likely reflects, in part, differences in vitamin D absorption and/or degradation. Despite this variation in response, virtually all expert recommendations endorse a fixed vitamin D supplementation dose, an approach also used in most prospective studies. Such utilization of a single vitamin D dose does not assure attaining any pre-specified target 25(OH)D level, thereby compromising clinical care and prospective supplementation trials. This study begins addressing this weakness by exploring the feasibility of vitamin D metabolite measurements to predict serum 25(OH)D level attained following supplementation. METHODS: Ninety-one community-dwelling postmenopausal women with baseline 25(OH)D of 10-30 ng/mL received oral vitamin D3, 2300 or 2500 IU, daily for 4-6 months. Serum 25(OH)D, cholecalciferol (D3), and 24,25(OH)2D were measured before and at the end of supplementation to determine if metabolite concentrations allow prediction of the 25(OH)D level attained. RESULTS: From baseline and follow-up data, we derived a multiple linear regression model predicting posttreatment 25(OH)D as follows: final 25(OH)D = 8.3 + (1.05*initial 25(OH)D) - (7.7*initial 24,25(OH)2D) + (0.53*final D3) + (4.2*final 24,25(OH)2D). This model has an adjusted R(2) = 0.55, thus accounting for approximately half of the observed variance in the final 25(OH)D level. CONCLUSIONS: The contributions of circulating cholecalciferol and 24,25(OH)2D to this predictive model can be considered as indicators of intestinal absorption and clearance, respectively. This paradigm requires further study; it may allow efficient "treat-to-25(OH)D-target" strategies useful in optimizing prospective studies and clinical practice.

Vitamin D deficiency in anesthesia department caregivers at the end of winter.

BACKGROUND: To test whether the vitamin D status of anesthesia department caregivers practicing at high Northern latitudes is compatible with current recommendations, the 25-hydroxyvitamin D (25(OH)D) levels of caregivers at hospitals in Iceland (64°08' N) and in Wisconsin (43°07' N) were compared at the end of winter. METHODS: Anesthesia department faculty and resident physicians, non-physician anesthetists, and critical care nurses completed a questionnaire, and provided blood samples for analysis of 25(OH)D by reverse-phase high performance liquid chromatography. RESULTS: One hundred and six participants in Iceland and 124 participants in Wisconsin were enrolled. No difference in mean serum 25(OH)D levels between Iceland [70.53 nmol/l, standard deviation (SD) 30.87 nmol/l] and Wisconsin (70.0 nmol/l, SD 30.0 nmol/l) was observed. In Iceland and Wisconsin, 25(OH)D levels below 25 nmol/l were observed in 4.7% and 4.0%, below 50 nmol/l in 34.9% and 25.0%, and below 75 nmol/l in 56.6% and 61.3% of caregivers, respectively. CONCLUSIONS: 25(OH)D levels below the 50 nmol/l (20 ng/ml) threshold recommended by the Institute of Medicine and the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis, and below the 75 nmol/l (30 ng/ml) threshold recommended by The Endocrine Society, are highly prevalent among anesthesia caregivers working at two Northern hospitals at the end of winter who may otherwise not meet criteria to be tested. Anesthesia and critical care providers may wish to determine their 25(OH)D levels and use effective, safe, and low cost supplementation to target a 25(OH)D level compatible with optimal health.

Rapid correction of low vitamin D status in nursing home residents.

UNLABELLED: This prospective study finds that ergocalciferol 50,000 IU three times weekly for four weeks effectively and safely corrects vitamin D inadequacy in nursing home residents. INTRODUCTION: Low vitamin D status is common among nursing home residents and contributes to bone loss, falls and fractures. The objective of this study was to evaluate the efficacy and safety of short course, high dose, oral vitamin D(2) (ergocalciferol) treatment. METHODS: This prospective study included 63 nursing home residents. The 25 with low vitamin D status (serum 25(OH)D < or = 25 ng/ml) received oral ergocalciferol 50,000 IU three times weekly for four weeks; the others received no change to their routine care. Serum total 25(OH)D, 25(OH)D(2), 25(OH)D(3), calcium, parathyroid hormone (PTH), bone turnover markers and neuro-cognitive assessments were obtained at baseline and four weeks. RESULTS: Mean total 25(OH)D concentration increased (p < 0.0001) from 17.3 to 63.8 ng/ml in the treated group and remained unchanged in the comparison group. Serum 25(OH)D(3) remained stable in the comparison group, but declined (p < 0.0001) with D(2) treatment from 15.4 to 9.1 ng/ml. Serum PTH trended down in the treatment group (p = 0.06). No treatment-induced improvement in ambulation, cognition or behavior was observed. No hypercalcemia or other adverse effects were observed with ergocalciferol treatment. CONCLUSION: Four weeks of oral vitamin D(2) supplementation effectively and safely normalizes serum 25(OH)D in nursing home residents.

Low vitamin D status despite abundant sun exposure.

CONTEXT: Lack of sun exposure is widely accepted as the primary cause of epidemic low vitamin D status worldwide. However, some individuals with seemingly adequate UV exposure have been reported to have low serum 25-hydroxyvitamin D [25(OH)D] concentration, results that might have been confounded by imprecision of the assays used. OBJECTIVE: The aim was to document the 25(OH)D status of healthy individuals with habitually high sun exposure. SETTING: This study was conducted in a convenience sample of adults in Honolulu, Hawaii (latitude 21 degrees ). PARTICIPANTS: The study population consisted of 93 adults (30 women and 63 men) with a mean (sem) age and body mass index of 24.0 yr (0.7) and 23.6 kg/m(2) (0.4), respectively. Their self-reported sun exposure was 28.9 (1.5) h/wk, yielding a calculated sun exposure index of 11.1 (0.7). MAIN OUTCOME MEASURES: Serum 25(OH)D concentration was measured using a precise HPLC assay. Low vitamin D status was defined as a circulating 25(OH)D concentration less than 30 ng/ml. RESULTS: Mean serum 25(OH)D concentration was 31.6 ng/ml. Using a cutpoint of 30 ng/ml, 51% of this population had low vitamin D status. The highest 25(OH)D concentration was 62 ng/ml. CONCLUSIONS: These data suggest that variable responsiveness to UVB radiation is evident among individuals, causing some to have low vitamin D status despite abundant sun exposure. In addition, because the maximal 25(OH)D concentration produced by natural UV exposure appears to be approximately 60 ng/ml, it seems prudent to use this value as an upper limit when prescribing vitamin D supplementation.

Vitamin K supplementation does not affect ovariectomy-induced bone loss in rats.

Vitamin K may be important in bone metabolism. Notably, high-dose menaquinone-4 (menatetrenone, MK4) has been reported to reduce ovariectomy (ovx)-induced bone loss in rats and to decrease osteoporotic fracture in postmenopausal women. However, it is unclear whether these beneficial effects reflect a physiologic effect of vitamin K, or indicate direct pharmacologic activity of MK4. To further evaluate this, 60 6-month-old nulliparous Sprague-Dawley rats were randomized by distal femur bone mineral density (BMD) in a 3:1 ratio to ovx or sham groups. The sham and one ovx group's diet contained 1% calcium and 1300 microg/kg of vitamin K1, phylloquinone. Diets of the other two ovx groups were supplemented with 882 mg phylloquinone or MK4 per kilogram chow. Distal femur bone mineral density (DFBMD) in an 8 mm region of interest was measured at baseline, 1 and 3 months postoperatively, utilizing dual-energy X-ray absorptiometry (DXA). All animals were killed at 3 months, their right femurs excised, ex vivo BMD measured by DXA, and biomechanical testing performed. No effect of phylloquinone or MK4 supplementation on ovx-induced bone loss was observed. Specifically, DFBMD declined 10.5%, 9.2%, and 11.2% at 1 month and 14.4%, 10.6%, and 13.9% at 3 months in the ovx control, high phylloquinone, and high MK4 groups, respectively. In addition, serum osteocalcin was elevated by ovx; this was not altered by phylloquinone or MK4. Finally, femoral biomechanical properties were not affected by phylloquinone or MK4. To conclude, in this study, neither high-dose phylloquinone nor MK4 reduced the ovx-associated increase in bone turnover or decline in DFBMD.

Vitamin K supplementation reduces serum concentrations of under-gamma-carboxylated osteocalcin in healthy young and elderly adults.

BACKGROUND: Subclinical vitamin K insufficiency, manifested by under-gamma-carboxylation of the bone matrix protein osteocalcin, may be common. OBJECTIVE: Our objective was to delineate the prevalence of submaximal gamma-carboxylation as assessed by response to phylloquinone supplementation and to evaluate the effect of this intervention on skeletal turnover in healthy North American adults. DESIGN: Healthy subjects (n = 219), approximately equally distributed by sex and age (18-30 y and >/=65 y), received daily phylloquinone (1000 microg) or placebo for 2 wk. Serum undercarboxylated osteocalcin (ucOC) and total osteocalcin, N:-telopeptides of type I collagen (NTx), bone-specific alkaline phosphatase (BSAP), and phylloquinone concentrations were measured at baseline and after weeks 1 and 2. RESULTS: At baseline, the mean serum phylloquinone concentration was lower in the young than in the old group; there was no effect of sex. Concomitantly, baseline %ucOC was highest in the young and lowest in the old men (P: < 0.0001) but did not differ significantly by age in women. After supplementation, serum phylloquinone concentration increased approximately 10-fold (P: < 0.0001) at week 1 (from 0.93 +/- 0.08 to 8.86 +/- 0.70 nmol/L, x+/- SEM); this was sustained through week 2. Among all supplemented groups, mean %ucOC decreased from 7.6% to 3. 4% without significant differences by age or sex; 102 of 112 subjects had a >1% decrease. Phylloquinone supplementation reduced serum osteocalcin but did not alter NTx or BSAP concentration. CONCLUSIONS: Usual dietary practices in this population did not provide adequate vitamin K for maximal osteocalcin carboxylation. Phylloquinone supplementation reduced serum osteocalcin concentration but did not alter other markers of serum bone turnover.

Diet- or warfarin-induced vitamin K insufficiency elevates circulating undercarboxylated osteocalcin without altering skeletal status in growing female rats.

To further characterize the skeletal role of vitamin K (K), markers of bone turnover, density, and strength were evaluated in rats with diet- or warfarin (W)-induced K insufficiency. One hundred two, 7-week-old, female rats were randomly assigned to low K (phylloquinone [K1], 20 microg/kg diet), control K (K1, 1300 microg/kg diet), low-dose W (W, 1.5 mg/kg control diet), or high-dose W plus K (W/K1, 10/100 mg/kg diet). Femur bone mineral content (BMC) and bone mineral density (BMD), plasma prothrombin time (PT) and prothrombin concentration (PC), and serum total alkaline phosphatase (ALP) and skeletal alkaline phosphatase (sALP) were measured at baseline and days 20, 40, 60, and 80. Serum total osteocalcin (OC) and undercarboxylated osteocalcin (ucOC) and femur length (FL) were measured at baseline and day 80. Left femur OC was measured and biomechanical testing of the right femur and third lumbar vertebral body was performed at day 80. Low dietary K elevated circulating ucOC (17% higher than control; p < 0.0001) at day 80. Furthermore, in both W groups, essentially all circulating OC was undercarboxylated and femur OC was lower than control (p < 0.0001). However, there was no change in femur percent ucOC, suggesting deposition of less newly synthesized OC. No between group differences were observed in PT, ALP, sALP, FL, BMC, BMD, or bone strength. In conclusion, skeletal K insufficiency can be induced by W or diet manipulation. This does not hinder peak bone mass attainment in female rats; however, W causes less newly synthesized OC to be deposited in bone.

Management of glucocorticoid-induced osteoporosis in male veterans.

OBJECTIVE: To determine whether glucocorticoid-induced osteoporosis in male veterans was managed in accordance with American College of Rheumatology (ACR) guidelines. These guidelines recommend bone mineral density (BMD) determination at the initiation of long-term therapy with prednisone > or =7.5 mg/d, provision of hormone replacement therapy as needed, calcium and vitamin D supplementation as necessary, and antiresorptive therapy for low BMD. DESIGN: Patients receiving prednisone > or =7.5 mg/d throughout a predefined six-month period were identified through a hospital pharmacy database. Electronic and paper chart review was carried out to determine whether BMD measurement by dual-energy X-ray absorptiometry had been performed. Supplemental calcium and vitamin D intake was assessed for each patient. In addition, pharmacy records were reviewed to determine whether antiresorptive therapy was prescribed for patients with low BMD. SETTING: The Wm. S. Middleton Veterans Affairs Medical Center, Madison, WI. RESULTS: Seventy-two men met study criteria. They had been receiving oral prednisone treatment for a median of 30 months (range 6-74); mean daily dosage during the six-month study period was 12.5 mg (range 7.5-37.5). Extensive record review revealed that only six patients (8%) received recommended calcium and vitamin D, and only 43 (60%) had a BMD determination. Of those 43 men, 32 had T-scores below -1, therefore meeting ACR criteria for recommended antiresorptive therapy. However, only 12 of these 32 patients were prescribed antiresorptive therapy. Although this study was not designed to evaluate differences among clinics, there appeared to be better adherence to ACR guidelines for patients cared for in a rheumatology specialty clinic than in other clinics at the institution. CONCLUSIONS: Adherence to ACR guidelines for management of glucocorticoid-induced osteoporosis was poor. Efforts to improve the prevention and management of glucocorticoid-induced osteoporosis in male veterans are warranted.

Comparison of phylloquinone bioavailability from food sources or a supplement in human subjects.

Phylloquinone (K) absorption was assessed in 22- to 30-y-old human subjects consuming a standard test meal [402 kcal (1682 kJ), 27% energy from fat]. The absorption of phylloquinone, measured over a 9-h period as the area under the curve (AUC), was higher (P < 0.01) after the consumption of a 500- microgram phylloquinone tablet [27.55 +/- 10.08 nmol/(L. h), n = 8] than after the ingestion of 495 microgram phylloquinone as 150 g of raw spinach [4.79 +/- 1.11 nmol/(L. h), n = 3]. Less phylloquinone (P < 0.05) was absorbed from 50 g of spinach (AUC = 2.49 +/- 1.11 nmol/(L. h) than from 150 g of spinach. Absorption of phylloquinone from fresh spinach (165 microgram K), fresh broccoli (184 microgram K) and fresh romaine lettuce (179 microgram K) did not differ. There was no difference in phylloquinone absorption from fresh or cooked broccoli or from fresh romaine lettuce consumed with a meal containing 30 or 45% energy as fat.

Effect of dehydroepiandrosterone sulfate on carnitine acetyl transferase activity and L-carnitine levels in oophorectomized rats.

Alteration in energy metabolism of postmenopausal women might be related to the reduction of dehydroepiandrosterone sulfate (DHEAS). DHEA and DHEAS decline with age, leveling at their nadir near menopause. DHEA and DHEAS modulate fatty acid metabolism by regulating carnitine acyltransferases and CoA. The purpose of this study was to determine whether dietary supplementation with DHEAS would also increase tissue L-carnitine levels, carnitine acetyltransferase (CAT) activity and mitochondrial respiration in oophorectomized rats. Plasma L-carnitine levels rose following oophorectomy in all groups (P < 0.0001). Supplementation with DHEAS was not associated with further elevation of plasma L-carnitine levels, but with increased hepatic total and free L-carnitine (P = 0.021 and P < 0.0001, respectively) and cardiac total L-carnitine concentrations (P = 0.045). In addition, DHEAS supplementation increased both hepatic and cardiac CAT activities (P < 0.0001 and P = 0.05 respectively). CAT activity positively correlated with the total and free carnitine levels in both liver and heart (r = 0.764, r = 0.785 and r = 0.700, r = 0.519, respectively). Liver mitochondrial respiratory control ratio, ADP:O ratio and oxygen uptake were similar in both control and supplemented groups. These results demonstrate that in oophorectomized rats, dietary DHEAS supplementation increases the liver and heart L-carnitine levels and CAT activities. In conclusion, DHEAS may modulate L-carnitine level and CAT activity in estrogen deficient rats. The potential role of DHEAS in the regulation of fatty acid oxidation in postmenopausal women is worthy of investigation.