Tag Archives: positive

Omega-3 Associated with Lumbar Spine BMD in Postmenopausal Women

Abstract

Association of n-3 polyunsaturated fatty acid intake with bone mineral density in postmenopausal women.

n-3 Polyunsaturated fatty acids (n-3 fatty acids) have been shown to have a beneficial effect on bone in animal studies, although little is known about their role in bone metabolism in humans. We investigated the association between bone mineral density (BMD) and daily n-3 fatty acid intake. This cross-sectional, community-based, epidemiologic study was conducted among 205 healthy postmenopausal women (mean age 63.5 years, range 46-79). We examined BMD, serum N-terminal propeptide of type I collagen (PINP), urinary type-I collagen cross-linked-N-telopeptide (uNTX), total cholesterol, triglycerides, and high-density lipoprotein cholesterol. Nutrient intake was calculated using a food-frequency questionnaire. BMD was measured at the lumbar spine and femoral neck by dual-energy X-ray absorptiometry. Simple regression analysis showed that intake of neither n-3 fatty acid nor n-6 fatty acid was associated with age or lipid metabolism indices. However, simple regression analysis showed that n-3 fatty acid intake was positively associated with both lumbar spine BMD and femoral neck BMD. n-6 fatty acid intake was positively associated with femoral neck BMD but not lumbar spine BMD. Multiple regression analysis showed that n-3 fatty acid intake was positively associated with lumbar spine BMD after adjustment for age, BMI, duration of menopausal state, grip strength, PINP, uNTX, and intakes of calcium, vitamin D, vitamin K, and n-6 fatty acid. In conclusion, n-3 fatty acid intake was positively associated with lumbar spine BMD independent of bone resorption and serum levels of cholesterol and triglycerides in postmenopausal women.

Nawata K, Yamauchi M, Takaoka S, Yamaguchi T…
Calcif. Tissue Int. Aug 2013
PMID: 23708886

EPA and DHA Improve Bone Properties in Mice

Abstract

Effects of long-term supplementation with omega-3 fatty acids on longitudinal changes in bone mass and microstructure in mice.

A diet rich in omega-3s has previously been suggested to prevent bone loss. However, evidence for this has been limited by short exposure to omega-3 fatty acids (FAs). We investigated whether a diet enriched in eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) for the entire adult life of mice could improve bone microstructure and strength. Thirty female mice received a diet enriched in DHA or EPA or an isocaloric control diet from 3 to 17 months of age. Changes in bone microstructure were analyzed longitudinally and biomechanical properties were analysed by a three-point bending test. Bone remodelling was evaluated by markers of bone turnover and histomorphometry. Trabecular bone volume in caudal vertebrae was improved by EPA or DHA at 8 months (+26.6% and +17.2%, respectively, compared to +3.8% in controls, P=.01), but not thereafter. Trabecular bone loss in the tibia was not prevented by omega-3 FAs (BV/TV -94%, -93% and -97% in EPA, DHA and controls, respectively). EPA improved femur cortical bone volume (+8.1%, P<.05) and thickness (+4.4%, P<.05) compared to controls. EPA, but not DHA, reduced age-related decline of osteocalcin (-70% vs. -83% in controls, P<.05). EPA and DHA increased leptin levels (7.3±0.7 and 8.5±0.5 ng ml⁻¹, respectively, compared to 4.5±0.9 ng ml⁻¹ in controls, P=.001); however, only EPA further increased IGF-1 levels (739±108 ng ml⁻¹, compared to 417±58 ng ml⁻¹ in controls, P=.04). These data suggest that long-term intake of omega-3 FA, particularly EPA, may modestly improve the structural and mechanical properties of cortical bone by an increase in leptin and IGF-1 levels, without affecting trabecular bone loss.

Bonnet N, Ferrari SL
J. Nutr. Biochem. Jul 2011
PMID: 21036590

Fish Oil, EPA + DHA Correlated with Bone Mass in Postmenopausal Korean Women

Abstract

Positive correlation between erythrocyte levels of n-3 polyunsaturated fatty acids and bone mass in postmenopausal Korean women with osteoporosis.

Osteoporosis, a major health problem among postmenopausal women, is influenced by dietary factors. The purpose of the present study was to evaluate the hypothesis that erythrocyte levels of n-3 polyunsaturated fatty acid (PUFA) and the dietary intake of fish are associated with risk of osteoporosis and correlate with bone mass in postmenopausal Korean women with the disease.
Fifty cases and 100 controls were recruited. Osteoporosis was defined according to the International Society for Clinical Densitometry guideline as a score lower than -2.5 SD below the T-score for lumbar vertebrae L₁-L₄, femoral neck or femoral total.
The T-score of the femoral neck was positively correlated with erythrocyte levels of n-3 PUFA, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and the intake of fish, and was negatively correlated with the ratio of n-6/n-3 PUFA after adjusting for age, years after menopause and height. In addition, the risk of osteoporosis was positively associated with erythrocyte levels of saturated fatty acids but negatively associated with EPA + DHA.
Erythrocyte levels of n-3 PUFA and the intake of fish were positively correlated with bone mass. In particular, erythrocyte levels of EPA + DHA reduced the risk of osteoporosis in postmenopausal Korean women.

Moon HJ, Kim TH, Byun DW, Park Y
Ann. Nutr. Metab. 2012
PMID: 22507833

DHA, Not EPA or DPA, Vital For Healthy Bones in Rats

Abstract

Bone mineral content is positively correlated to n-3 fatty acids in the femur of growing rats.

The present study was conducted to determine whether provision of preformed dietary docosapentaenoic acid (DPAn-6) can replace DHA for normal long bone growth as assessed by dual-energy X-ray absorptiometry for mineral content (BMC). A newly modified artificial rearing method was employed to generate n-3 fatty acid-deficient rats. Except the dam-reared (DR; 3.1 % alpha-linolenic acid) group, newborn pups were separated from their mothers at age 2 d and given artificial rat milk containing linoleic acid (LA), or LA supplemented with 1 % DHA (22 : 6n-3; DHA), 1 % DPAn-6 (DPA), or 1 % DHA plus 0.4 % DPAn-6 (DHA/DPA). The rats were later weaned onto similar pelleted diets. At adulthood, the rats were euthanised and bones (femur, tibia, and lumbar vertebrae) collected for tissue fatty acid analysis and bone mineral density (BMD) determination. The analyses showed that long bones such as femur and tibia in DPAn-6-treated rats contained higher DPAn-6 content and generally had the lowest BMC and BMD values. Hence, DPAn-6 did not replace DHA for normal bone growth and maximal BMC in femur, indicating an indispensible role of DHA in bone health. In conclusion, DHA accumulates in the osteoblast-rich and nerve-abundant periosteum of femur; DHA but not EPA appears to be a vital constituent of marrow and periosteum of healthy modelling bone; and both DHA and total n-3 PUFA strongly correlate to BMC.

Li Y, Seifert MF, Lim SY, Salem N…
Br. J. Nutr. Sep 2010
PMID: 20420751

EPA + DHA Have Favorable Effect on Bone Density and Strength in Mice

Abstract

Femur EPA and DHA are correlated with femur biomechanical strength in young fat-1 mice.

Evidence suggests that n-3 polyunsaturated fatty acids (PUFA) are beneficial for maintenance of bone health and possibly bone development. This study used the fat-1 mouse, a transgenic model that synthesizes n-3 PUFA from n-6 PUFA, to determine if outcomes of bone health were correlated with n-3 PUFA in femurs. Control and fat-1 mice were fed an AIN-93G diet containing 10% safflower oil from weaning through 12 weeks of age. Femur bone mineral content (BMC) and density were determined by dual-energy X-ray absorptiometry, and biomechanical strength properties, surrogate measures of fracture risk, were measured by a materials testing system. Femur fatty acid composition was determined by gas chromatography. At 12 weeks of age, femur n-3 PUFA were higher among fat-1 mice compared to control mice. The n-6/n-3 PUFA ratio in the femur was negatively correlated with BMC (r=-.57, P=.01) and peak load at femur midpoint (r=-.53, P=.02) and femur neck (r=-.52, P=.02). Moreover, long-chain n-3 PUFA, eicosapentaenoic acid, and docosahexaenoic acid were significantly and positively correlated or displayed a trend suggesting positive correlations, with BMC and peak load. In conclusion, the results of the present study suggest that n-3 PUFA have a favorable effect on mineral accumulation and functional measures of bone in fat-1 mice at young adulthood.

Lau BY, Ward WE, Kang JX, Ma DW
J. Nutr. Biochem. Jun 2009
PMID: 18708283

Fish Oil Decreases Bone Loss in Ovariectomized Mice

Abstract

Dietary n-3 fatty acids decrease osteoclastogenesis and loss of bone mass in ovariectomized mice.

The mechanisms of action of dietary fish oil (FO) on osteoporosis are not fully understood. This study showed FO decreased bone loss in ovariectomized mice because of inhibition of osteoclastogenesis. This finding supports a beneficial effect of FO on the attenuation of osteoporosis.
Consumption of fish or n-3 fatty acids protects against cardiovascular and autoimmune disorders. Beneficial effects on bone mineral density have also been reported in rats and humans, but the precise mechanisms involved have not been described.
Sham and ovariectomized (OVX) mice were fed diets containing either 5% corn oil (CO) or 5% fish oil (FO). Bone mineral density was analyzed by DXA. The serum lipid profile was analyzed by gas chromatography. Receptor activator of NF-kappaB ligand (RANKL) expression and cytokine production in activated T-cells were analyzed by flow cytometry and ELISA, respectively. Osteoclasts were generated by culturing bone marrow (BM) cells with 1,25(OH)2D3. NF-kappaB activation in BM macrophages was measured by an electrophoretic mobility shift assay.
Plasma lipid C16:1n6, C20:5n3, and C22:6n3 were significantly increased and C20:4n6 and C18:2n6 decreased in FO-fed mice. Significantly increased bone mineral density loss (20% in distal left femur and 22.6% in lumbar vertebrae) was observed in OVX mice fed CO, whereas FO-fed mice showed only 10% and no change, respectively. Bone mineral density loss was correlated with increased RANKL expression in activated CD4+ T-cells from CO-fed OVX mice, but there was no change in FO-fed mice. Selected n-3 fatty acids (docosahexaenoic acid [DHA] and eicosapentaenoic acid [EPA]) added in vitro caused a significant decrease in TRACP activity and TRACP+ multinuclear cell formation from BM cells compared with selected n-6 fatty acids (linoleic acid [LA] and arachidonic acid [AA]). DHA and EPA also inhibited BM macrophage NF-kappaB activation induced by RANKL in vitro. TNF-alpha, interleukin (IL)-2, and interferon (IFN)-gamma concentrations from both sham and OVX FO-fed mice were decreased in the culture medium of splenocytes, and interleukin-6 was decreased in sham-operated FO-fed mice. In conclusion, inhibition of osteoclast generation and activation may be one of the mechanisms by which dietary n-3 fatty acids reduce bone loss in OVX mice.

Sun D, Krishnan A, Zaman K, Lawrence R…
J. Bone Miner. Res. Jul 2003
PMID: 12854830

EPA + GLA Increases Bone Density in Elderly Women

Abstract

Calcium, gamma-linolenic acid and eicosapentaenoic acid supplementation in senile osteoporosis.

Recent animal work suggests that gamma-linolenic acid (GLA) and eicosapentaenoic acid (EPA) enhance calcium absorption, reduce excretion and increase calcium deposition in bone. A pilot study was set up to test the interactions between calcium and GLA + EPA in humans. Sixty-five women (mean age 79.5), taking a background diet low in calcium, were randomly assigned to GLA + EPA or coconut oil placebo capsules; in addition, all received 600 mg/day calcium as the carbonate. Markers of bone formation/degradation and bone mineral density (BMD) were measured at baseline, 6, 12 and 18 months. Twenty-one patients were continued on treatment for a second period of 18 months, after which BMD (36 months) was measured. At 18 months, osteocalcin and deoxypyridinoline levels fell significantly in both groups, indicating a decrease in bone turnover, whereas bone specific alkaline phosphatase rose indicating beneficial effects of calcium given to all the patients. Lumbar and femoral BMD, in contrast, showed different effects in the two groups. Over the first 18 months, lumbar spine density remained the same in the treatment group, but decreased 3.2% in the placebo group. Femoral bone density increased 1.3% in the treatment group, but decreased 2.1% in the placebo group. During the second period of 18 months with all patients now on active treatment, lumbar spine density increased 3.1% in patients who remained on active treatment, and 2.3% in patients who switched from placebo to active treatment; femoral BMD in the latter group showed an increase of 4.7%. This pilot controlled study suggests that GLA and EPA have beneficial effects on bone in this group of elderly patients, and that they are safe to administer for prolonged periods of time.

Kruger MC, Coetzer H, de Winter R, Gericke G…
Aging (Milano) Oct 1998
PMID: 9932142

EPA + DHA, but Especially EPA, Effective in Diabetic Rats with Osteopenia

Abstract

Effect of eicosapentaenoic acid and docosahexaenoic acid on diabetic osteopenia.

To evaluate the effect of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which are polyunsaturated fatty acids, on diabetic osteopenia, we measured the bone fragility in streptozotocin-induced diabetic rats. The fragility of femur was increased in diabetic rats, which was prevented in part by EPA or DHA. Moreover, EPA prevented osteopenia even in diabetic rats fed a low zinc feed, which was a potent accelerator of diabetic osteopenia. Plasma alkaline phosphatase activity and parathyroid hormone level showed no difference between the two groups of diabetic rats with or without EPA. Urinary excretion of calcium and phosphate was increased and plasma inorganic phosphate level was high in diabetic rats, suggesting severe mineral loss. In diabetic rats fed EPA, although urinary and plasma calcium levels did not change significantly, urinary phosphate excretion and plasma inorganic phosphate concentration were slightly lowered, which suggested that EPA may have an effect in suppressing phosphate release from bones in diabetic rats. These data suggest that EPA and DHA could be effective on diabetic osteopenia, but to elucidate the precise mechanisms, further examinations will be needed.

Yamada Y, Fushimi H, Inoue T, Matsuyama Y…
Diabetes Res. Clin. Pract. Oct 1995
PMID: 8745204

Higher Omega-3, but Especially DHA, Preserve Bone in Ovariectomized Rats

Abstract

Dietary ratio of n-6/n-3 PUFAs and docosahexaenoic acid: actions on bone mineral and serum biomarkers in ovariectomized rats.

Hypoestrogenic states escalate bone loss in animals and humans. This study evaluated the effects of the amount and ratio of dietary n-6 and n-3 polyunsaturated fatty acids (PUFAs) on bone mineral in 3-month-old sexually mature ovariectomized (OVX) Sprague-Dawley rats. For 12 weeks, the rats were fed either a high-PUFA (HP) or a low-PUFA (LP) diet with a ratio of n-6/n-3 PUFAs of 5:1 (HP5 and LP5) or 10:1 (HP10 and LP10). All diets (modified AIN-93G) provided 110.4 g/kg of fat from safflower oil and/or high-oleate safflower oil blended with n-3 PUFAs (DHASCO oil) as a source of docosahexaenoic acid (DHA). Fatty acid analyses confirmed that the dietary ratio of 5:1 significantly elevated the amount of DHA in the periosteum, marrow and cortical and trabecular bones of the femur. Dual-energy X-ray absorptiometry measurements for femur and tibia bone mineral content (BMC) and bone mineral density showed that the DHA-rich diets (HP5 and LP5) resulted in a significantly lower bone loss among the OVX rats at 12 weeks. Rats fed the LP diets displayed the lowest overall serum concentrations of the bone resorption biomarkers pyridinoline (Pyd) and deoxypyridinoline, whereas the bone formation marker osteocalcin was lowest in the HP groups. Regardless of the dietary PUFA content, DHA in the 5:1 diets (HP5 and LP5) preserved rat femur BMC in the absence of estrogen. This study indicates that the dietary ratio of n-6/n-3 PUFAs (LP5 and HP5) and bone tissue concentration of total long-chain n-3 PUFAs (DHA) minimize femur bone loss as evidenced by a higher BMC in OVX rats. These findings show that dietary DHA lowers the ratio of 18:2n-6 (linoleic acid)/n-3 in bone compartments and that this ratio in tissue correlates with reduced Pyd but higher bone alkaline phosphatase activity and BMC values that favor bone conservation in OVX rats.

Watkins BA, Li Y, Seifert MF
J. Nutr. Biochem. Apr 2006
PMID: 16102959

Fish Oil, Especially DHA, Increases Bone Density in Rats

Abstract

Is docosahexaenoic acid more effective than eicosapentaenoic acid for increasing calcium bioavailability?

Experimental animal and human studies have indicated that long chain polyunsaturated fatty acids (LCPUFA) may enhance calcium absorption, reduce urinary calcium excretion, and increase bone calcium content. In the present study, the effect of LCPUFA, as provided in evening primrose oil, fish and tuna oils, on calcium bioavailability was investigated. Growing male rats were fed a semi-synthetic diet for 6 weeks, after which calcium absorption, bone mineral density (ex vivo), bone calcium content, and bone biomechanics were measured. Calcium absorption, ex vivo bone mineral density, and bone calcium content were significantly higher in the animals fed tuna oil compared with those of a control group fed corn oil. Significant correlations were found between the docosahexaenoic acid (DHA) (22:6n-3) content of the red cell membranes and bone density and bone calcium content. DHA increased accretion of calcium in bone significantly more so than eicosapentaenoic acid (EPA) (20:5n-3).

Kruger MC, Schollum LM
Prostaglandins Leukot. Essent. Fatty Acids Nov 2005
PMID: 16154334