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Folate + B12 Offer No Sensomotor Speed Benefit Despite Decreasing Homocysteine

Abstract

The association of betaine, homocysteine and related metabolites with cognitive function in Dutch elderly people.

The importance of the one-carbon metabolites, choline and homocysteine, to brain function is well known. However, the associations between the one-carbon metabolites choline, betaine, methionine and dimethylglycine with cognition in elderly are unclear. We therefore examined the associations of these metabolites with cognition in a double-blind, placebo-controlled trial. Individuals (n 195) were randomized to receive daily oral capsules with either 1000 microg cobalamin (vitamin B12), or 1000 microg cobalamin plus 400 microg folic acid, or placebo for 24 weeks. Concentrations of homocysteine, methionine, choline, betaine and dimethylglycine were assessed before and after 12 and 24 weeks of treatment. Cognitive function, including domains of attention, construction, sensomotor speed, memory and executive function, was assessed before and after 24 weeks of treatment. At baseline, elevated plasma homocysteine was associated with lower performance of attention, construction, sensomotor speed and executive function. In addition, betaine was positively associated with better performance of construction, sensomotor speed and executive function, whereas elevated concentrations of methionine were positively associated with sensomotor speed. Daily combined supplementation with cobalamin plus folic acid decreased total homocysteine concentrations by 36%, and increased betaine concentrations by 38%. Participants with the largest increases in betaine concentrations showed a borderline significant (P = 0.07) higher memory performance compared to those without it. Although this trial observed associations of homocysteine and betaine with cognitive domains prior to supplementation, decreased concentrations of homocysteine were not related to improved cognitive performance. There was a tendency of participants with the largest increases in betaine concentrations to show the greatest improvement in memory function.

Eussen SJ, Ueland PM, Clarke R, Blom HJ…
Br. J. Nutr. Nov 2007
PMID: 17537289

Folic Acid and B12 Lowers Homocysteine but not Bone Turnover

Abstract

Folic acid and vitamin B(12) supplementation lowers plasma homocysteine but has no effect on serum bone turnover markers in elderly women: a randomized, double-blind, placebo-controlled trial.

An elevated homocysteine level is a newly recognized risk factor for osteoporosis. Older individuals may have elevated homocysteine levels due to inadequate folate intake and/or lower absorption of vitamin B(12). The aim of this study was to determine whether there is an impact of folic acid and vitamin B(12) supplementation on homocysteine levels and, subsequently, on bone turnover markers in older women with mildly to moderately elevated homocysteine levels. It is hypothesized that supplementation with folic acid and vitamin B(12) will improve homocysteine levels and, in turn, positively modify bone turnover markers in this population. This randomized, double-blind, placebo-controlled trial included 31 women (65 to 93 years) with homocysteine levels greater than 10 μmol/L. Participants were randomly assigned to receive either a daily folic acid (800 μg) and vitamin B(12) (1000 μg) (n = 17) or a matching placebo (n = 14) for 4 months. The results showed significantly lower homocysteine concentrations in the vitamin group compared to the placebo group (10.6 vs 18.5 μmol/L, P = .007). No significant difference in serum alkaline phosphatase or C-terminal cross-linking telopeptide of type I collagen was found between the vitamin and placebo groups before or after supplementation. The use of folic acid and vitamin B(12) as a dietary supplement to improve homocysteine levels could be beneficial for older women, but additional research must be conducted in a larger population and for a longer period to determine if there is an impact of supplementation on bone turnover markers or other indicators of bone health.

Keser I, Ilich JZ, Vrkić N, Giljević Z…
Nutr Res Mar 2013
PMID: 23507227

AKG Unimpressive in Omeprazole-Induced Bone Loss in Rats

Abstract

Can 2-oxoglutarate prevent changes in bone evoked by omeprazole?

Proton-pump inhibitors, such as omeprazole, are widely used in the prevention and treatment of gastroesophageal diseases. However, an association between proton-pump inhibitors and the increased risk of bone fractures has been observed, especially in patients treated for extended periods. Conversely, 2-oxoglutarate, a precursor of hydroxyproline, the most abundant amino acid in bone collagen, counteracts the bone loss. The aim of the present study was to elucidate the influence of omeprazole on bone and investigate whether dietary 2-oxoglutarate supplementation could prevent the effects of omeprazole.
Eighteen male Sprague-Dawley rats were used. Rats received omeprazole in the diet and 2-oxoglutarate in the drinking water. Body and organ weights and serum concentrations of cholecystokinin and gastrin were measured. The femurs, tibias, and calvarias were collected. Histomorphometric analysis of bone and cartilage tissues was conducted. Bone densitometric and peripheral quantitative computed tomographic analyses of the femur and tibia were performed.
Omeprazole decreased the femur and tibia weights, the mechanical properties of the femur, the volumetric bone density and content, the trabecular and cortical bone mineral content, the total, trabecular, and cortical bone areas, the mean cortical thickness, and the periosteal circumference of the femur. Omeprazole had a minor effect on the examined bone morphology and exerted negligible effects on the cartilage. 2-Oxoglutarate lowered the gastrin concentration.
Omeprazole treatment exerts its effects mostly on bone mineralization and cancellous bone, adversely affecting bone properties. This adverse effect of omeprazole was not markedly abolished by 2-oxoglutaric acid, which acted as an anti-hypergastrinemic agent.

Dobrowolski P, Tomaszewska E, Radzki RP, Bienko M…
Nutrition Mar 2013
PMID: 23218481

Lipids not Associated with Bone Density in Korean Women

Abstract

Association between Serum Cholesterol Level and Bone Mineral Density at Lumbar Spine and Femur Neck in Postmenopausal Korean Women.

Blood lipid profiles have been suggested to be a risk factor for osteoporosis. However, the association between lipid profiles and bone mineral density (BMD) is still unclear. This study aimed to evaluate an association between blood lipid profiles and BMD through both a cross-sectional and a longitudinal study.
Study subjects were 958 postmenopausal Korean women who have repeatedly undertaken laboratory tests and BMD measurements at lumbar spine and femur neck with an interval of 7.1 years. The associations between lipid profiles and BMD were examined using Spearman correlation analysis with an adjustment for age, smoking, alcohol drinking, physical activity, body mass index, and follow-up duration.
Lumbar spine BMD was not associated with total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), and high density lipoprotein cholesterol (HLD-C) regardless of when the measurement was performed. In an analysis using data measured at the beginning of the study, femur neck BMD was not associated with TC and LDL-C. However, femur neck BMD showed weak but significantly positive correlation with HDL-C (correlation coefficient, 0.077; 95% confidence interval, 0.005 to 0.149). When the analysis was repeated with data measured at the end of the follow-up, there was no significant correlation between femur neck BMD and any lipid profile. In addition, change in femur neck BMD during follow-up was not associated with the change in lipid profiles.
Although further study with a consideration of calcium intake and osteoporosis medication seems necessary, this study found no association between serum lipid profiles and BMD in postmenopausal Korean women.

Go JH, Song YM, Park JH, Park JY…
Korean J Fam Med May 2012
PMID: 22787539 | Free Full Text

Vitamin E Does Not Improve Bone Density in Rats

Abstract

The role of vitamin E in reversing bone loss.

A positive correlation between intake of antioxidants including vitamins E and C on bone mass has been established by a number of investigators. The present study was conducted to evaluate the extent to which higher doses of vitamin E than normal dose (75 IU per kg diet) can reverse bone loss in aged osteopenic orchidectomized male rats.
Forty 12-month old male Sprague- Dawley rats were either sham-operated (Sham) or orchidectomized (Orx), and fed control diet for 120 days to establish bone loss. Thereafter, rats were assigned to their corresponding treatment groups (n= 10 per group): Sham and one Orx groups received 75 IU vitamin E and served as controls, and the other two Orx groups received either 250 or 500 IU vitamin E per kg diet for 90 days.
Higher doses of vitamin E did not improve bone mineral density (BMD) or content (BMC) of whole body, femur and lumbar vertebra or alter the orchidectomy-induced deterioration of trabecular microarchitecture of the distal femur metaphysis in comparison with Orx controls that received adequate vitamin E. Biochemical markers of bone formation and bone resorption, i.e. serum osteocalcin and urinary deoxypyridinoline crosslinks, were also unaffected by vitamin E supplementation.
Overall, the findings of the present study suggest that supplemental doses of vitamin E do not increase BMD values in male rat model of osteoporosis. However, human studies are needed to confirm the population findings indicating that individuals with higher vitamin E intake have higher bone mass.

Chai SC, Wei CI, Brummel-Smith K, Arjmandi BH
Aging Clin Exp Res Dec 2008
PMID: 19179835

Mediterranean Diet + Nuts Does Not Significantly Increase Resorption

Abstract

Mediterranean diet and high dietary acid load associated with mixed nuts: effect on bone metabolism in elderly subjects.

Objectives: To analyze the effect of differing diet on the acid load content on bone metabolism.
Design: Multicentric, randomized, single-blind, parallel-group clinical trial.
Setting: Outpatient clinics.
Two hundred thirty-eight elderly men and women aged 60 to 80 at high risk for cardiovascular disease were randomly assigned to three interventional groups: a recommended low-fat diet (control diet group), a Mediterranean diet supplemented with virgin olive oil, or a Mediterranean diet supplemented with mixed nuts.
Main outcomes were 12-month changes from baseline in bone formation and resorption markers and bone mass measured according to quantitative ultrasound scanning.
The baseline data on the anthropometric, bone densitometry, and biochemical variables did not differ between the three groups. Dietary potential renal acid load (PRAL) and daily net endogenous acid production (NEAP) at baseline did not differ between groups. After intervention, subjects allocated to the Mediterranean diet with mixed nuts had a significant increase of PRAL and NEAP. In comparison, subjects in the Mediterranean diet with nuts group had higher parathyroid hormone (PTH) levels (2.63, 95% confidence interval (CI)=-1.01-6.35, P=.02) and a nonsignificantly higher (0.31, 95% CI=-0.13-0.74, P=.14) urine free deoxypyridoxine:creatinine ratio, a marker of bone resorption, than the control group and the Mediterranean diet with virgin olive oil group.
A Mediterranean dietary pattern associated with a high dietary acid load derived from consumption of mixed nuts does not seem to have a much greater effect on bone metabolism biomarkers, with the exception of PTH levels, than a Mediterranean diet without mixed nuts or a control diet in elderly subjects.

Bulló M, Amigó-Correig P, Márquez-Sandoval F, Babio N…
J Am Geriatr Soc Oct 2009
PMID: 19807791

Fish or Fish Oil No Association With Fracture – 2010

Abstract

Fish consumption, bone mineral density, and risk of hip fracture among older adults: the cardiovascular health study.

Marine n-3 polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may be beneficial for bone health, but few studies have investigated the association with fish consumption. Our aim was to study associations of fish and EPA + DHA consumption with bone mineral density (BMD) and hip fracture risk and determine whether high linoleic acid (LA) intake, the major dietary n-6 PUFA, modifies the associations. The study population consisted of 5045 participants aged 65 years and older from the Cardiovascular Health Study. Data on BMD were available for 1305 participants. Food-frequency questionnaire was used to assess dietary intake, and hip fracture incidence was assessed prospectively by review of hospitalization records. After multivariable adjustment, femoral neck BMD was 0.01 g/cm(2) lower in the highest versus lowest tuna/other-fish intake category (p = .05 for trend). EPA + DHA intake (higher versus lower median of 0.32 g/day) was associated with lower femoral neck BMD (0.66 versus 0.71 g/cm(2), p < .001) among those with LA intake greater than the median 12.1 g/day (p = .03 for interaction). No significant associations were found with total-hip BMD. During mean follow-up of 11.1 years, 505 hip fractures occurred. Fish or EPA + DHA consumption was not significantly associated with fracture incidence [hazard ratio (HR) for extreme categories: HR = 1.23, 95% confidence interval (CI) 0.83-1.84 for tuna/other fish; HR = 1.16, 95% CI 0.91-1.49 for fried fish; and HR = 0.98, 95% CI 0.71-1.36 for EPA + DHA]. High LA intake did not modify these associations. In this large prospective cohort of older adults, fish consumption was associated with very small differences in BMD and had no association with hip fracture risk.

Virtanen JK, Mozaffarian D, Cauley JA, Mukamal KJ…
J. Bone Miner. Res. Sep 2010
PMID: 20572022 | Free Full Text

Protein Supplement in Hip Rehabilitation Not Significant

Abstract

Provision of high-protein supplement for patients recovering from hip fracture.

We compared clinical outcomes with a standard (Ensure) or a high-protein (Boost HP) liquid nutritional supplement for older adults recovering from hip fracture surgery in a rehabilitation hospital. This randomized, double-blind, parallel-group study compared the clinical effectiveness of a standard (Ensure) with a high-protein (Boost HP) liquid nutritional supplement among patients (n = 46) 60 y or older who recently underwent surgical repair of a hip fracture. Patients were encouraged to drink at least two 8-oz cans (17.8 g/d protein for Ensure versus 30 g/d protein for Boost HP) per day for 28 d. Study measurements included change in Functional Independence Measure between rehabilitation admission and discharge, length of rehabilitation stay, laboratory measures (i.e., serum albumin, prealbumin, and C-reactive protein), physical activity energy expenditure by 7-d triaxial accelerometry, and dietary intake by three random, telephonic, 24-h dietary recalls.
There were no significant group differences with respect to age, sex, acute hospital days, hip fracture assessment parameters, or surgical treatment. Consumption of supplement (260 oz/28 d of Ensure versus 239 oz/28 d of Boost HP) was comparable. There were no differences in complication or adverse event rates during the study. The Boost HP group consumed more protein than the Ensure group (63 versus 50 g, P < 0.048) and had a greater improvement in serum albumin over the 28-d supplementation period (+0.7 versus +0.2 g/dL, P < 0.019). The Boost HP group also consumed more fiber (12 versus 8 g), calcium (821 versus 639 mg), vitamin K (66 versus 45 microg), and phosphorus (1035 versus 833 mg) than did the Ensure group. Rehabilitation length of stay was shorter in the Boost HP than in the Ensure group, although this trend did not reach statistical significance (23 versus 28 d, P = 0.27). Outcome differences were not detected in the Functional Independence Measure.
Supplementation was well tolerated in this population and contributed significantly to total dietary intake. Consumption of a high-protein liquid nutritional supplement may offer some benefits by improving visceral protein status.

Neumann M, Friedmann J, Roy MA, Jensen GL
Nutrition May 2004
PMID: 15105027

Daidzein Alone Did Not Preserve Trabecular Bone in Ovariectomized Mice

Abstract

Daidzein together with high calcium preserve bone mass and biomechanical strength at multiple sites in ovariectomized mice.

As the prevalence of osteoporosis is increasing, and the adverse effects of hormone replacement therapy are evident, women are searching for natural alternatives such as soy isoflavones to help prevent postmenopausal osteoporosis. Daidzein is one of the most abundant isoflavones present in soy and it is unique as it can be further metabolized to equol, a compound with greater estrogenic activity than other isoflavones. The objective of this study was to determine the effects of purified daidzein in combination with high calcium (Ca) on preserving femur and lumbar vertebrae (LV1-LV4) bone mineral density (BMD) and biomechanical bone strength at three different sites (femur midpoint, femur neck and LV3) in ovariectomized mice. Sham (SH) mice (n = 12) received control diet (AIN93G) containing 2 g Ca/kg diet and ovariectomized mice were randomized to 1 of 6 groups (n = 12/group): OVX (2 g Ca/kg diet), HCa (25 g Ca/kg diet), HD (2 g Ca + 200 mg daidzein/kg diet), HDCa (25 g Ca + 200 mg daidzein/kg diet), LD (2 g Ca + 100 mg daidzein/kg diet) or LDCa (25 g Ca + 100 mg daidzein/kg diet) for 12 weeks. HDCa preserved femur and vertebrae BMD and biomechanical bone strength (at all three sites) compared to the OVX group, however, only femur yield load (at midpoint) was preserved to a level that was greater (P < 0.05) than HCa alone. Mice fed HD diet had greater (P < 0.05) femur BMD than OVX group, however, daidzein alone (HD) did not appear to preserve trabecular bone (i.e., vertebrae BMD and vertebra peak load). All mice fed daidzein produced equol and there were no uterotrophic effects of daidzein at either dose. Both daidzein and Ca attenuated the increase in serum IL-1beta observed in the OVX group. The results from this study suggest that the combination of daidzein and high Ca favorably affect cortical and trabecular bone as indicated by femur and lumbar vertebrae BMD and biomechanical strength but much of this effect is mediated by the high Ca diet. Further investigation is required to determine optimal dietary levels of daidzein and Ca with the long-term goal of developing a dietary strategy to prevent postmenopausal osteoporosis and related fragility fractures.

Fonseca D, Ward WE
Bone Aug 2004
PMID: 15268901

CLA No Help in Athletes

Abstract

Effects of conjugated linoleic acid supplementation during resistance training on body composition, bone density, strength, and selected hematological markers.

Conjugated linoleic acids (CLA) are essential fatty acids that have been reported in animal studies to decrease catabolism, promote fat loss, increase bone density, enhance immunity, and serve as an antiatherogenic and anticarcinogenic agent. For this reason, CLA has been marketed as a supplement to promote weight loss and general health. CLA has also been heavily marketed to resistance-trained athletes as a supplement that may help lessen catabolism, decrease body fat, and promote greater gains in strength and muscle mass during training. Although basic research is promising, few studies have examined whether CLA supplementation during training enhances training adaptations and/or affects markers of health. This study evaluated whether CLA supplementation during resistance training affects body composition, strength, and/or general markers of catabolism and immunity. In a double-blind and randomized manner, 23 experienced, resistance-trained subjects were matched according to body mass and training volume and randomly assigned to supplement their diet with 9 g;pdd(-1) of an olive oil placebo or 6 g;pdd(-1) of CLA with 3 g;pdd(-1) of fatty acids for 28 days. Prior to and following supplementation, fasting blood samples, total body mass, and dual-energy X-ray absorptiometry (DEXA) determined body composition, and isotonic bench press and leg press 1 repetition maximums (1RMs) were determined. Results revealed that although some statistical trends were observed with moderate to large effect sizes, CLA supplementation did not significantly affect (p > 0.05) changes in total body mass, fat-free mass, fat mass, percent body fat, bone mass, strength, serum substrates, or general markers of catabolism and immunity during training. These findings indicate that CLA does not appear to possess significant ergogenic value for experienced resistance-trained athletes.

Kreider RB, Ferreira MP, Greenwood M, Wilson M…
J Strength Cond Res Aug 2002
PMID: 12173945