Category Archives: Omega-3

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

Fish Oil Reduces Resorption in Rats with Periodontal Disease

Abstract

Omega-3 fatty acid effect on alveolar bone loss in rats.

Gingival inflammation and alveolar bone resorption are hallmarks of adult periodontitis, elicited in response to oral micro-organisms such as Porphyromonas gingivalis. We hypothesized that omega (omega)-3 fatty acids (FA) dietary supplementation would modulate inflammatory reactions leading to periodontal disease in infected rats. Rats were fed fish oil (omega-3 FA) or corn oil (n-6 FA) diets for 22 weeks and were infected with P. gingivalis. Rats on the omega-3 FA diet exhibited elevated serum levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), documenting diet-induced changes. PCR analyses demonstrated that rats were orally colonized by P. gingivalis; increased IgG antibody levels substantiated this infection. P. gingivalis-infected rats treated with omega-3 FA had significantly less alveolar bone resorption. These results demonstrated the effectiveness of an omega-3 FA-supplemented diet in modulating alveolar bone resorption following P. gingivalis infection, and supported that omega-3 FA may be a useful adjunct in the treatment of periodontal disease.

Kesavalu L, Vasudevan B, Raghu B, Browning E…
J. Dent. Res. Jul 2006
PMID: 16798867

Statins and Fish Oil Improve Lipid in Bones

Abstract

Statins and dietary fish oils improve lipid composition in bone marrow and joints.

There have been numerous efforts to alter the lipid content of cardiovascular tissues. Although equally important, only limited information is available about musculoskeletal tissues. I characterized joint and bone marrow lipids in patients having joint replacement surgery and explored the effects of fish oils and statins on lipid composition in bone marrow and joint fluid. Joint drainage catheters were used to collect marrow lipids from 84 patients having 128 hip and knee replacements for osteoarthritis, osteonecrosis, and femoral neck fractures (osteoporosis). Statins reduced the amount of lipid by 22% in patients with osteoporosis, 26% in patients with osteoarthritis, and 41% in patients with osteonecrosis compared with pretreatment lipid levels in the same patients. Taking fish oils reduced the amount of lipid in bone marrow by 20%. Lipid profiles of disturbed marrow and joint fluid from patients who took statins or dietary fish oil showed an increase in the proportion of unsaturated fatty acids and longer-chain fatty acids relative to pretreatment profiles. The ability to change the amount and character of bone and joint lipids may have major importance for strengthening bone, reducing the severity or preventing osteonecrosis, and enhancing joint lubrication.

Pritchett JW
Clin. Orthop. Relat. Res. Mar 2007
PMID: 17496750

DHA More Potent Inhibitor of Osteoclasts than EPA

Abstract

Docosahexaenoic acid is more potent inhibitor of osteoclast differentiation in RAW 264.7 cells than eicosapentaenoic acid.

Fish oil rich in n-3 polyunsaturated fatty acids, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) protects inflammation induced bone loss in chronic inflammatory diseases like rheumatoid arthritis, periodontitis, and osteoporosis. EPA and DHA differentially regulate functional parameters and gene expression in different cell types. One of the risk factors for bone loss in inflammatory bone diseases is the elevation of bone-resorbing osteoclasts and a very few studies so far have indicated that attenuation of osteoclastogenesis might be one of the mechanisms by which n-3 PUFA exert its effect on bone loss protection. However, the precise mechanism underlying this process remains unclear. Receptor activator of NF-kappaB ligand (RANKL) is known to be the most critical mediator of osteoclastogenesis. Therefore, in this study, we examined the differential effect of EPA and DHA on RANKL-stimulated osteoclastogenesis and RANKL signaling using a murine monocytic cell line RAW 264.7. DHA was found to inhibit osteoclast differentiation, activation and function more potently than EPA. The differential potential also closely correlated with the inhibition of osteoclast-specific genes like tartrate resistant acid phosphatase, cathepsin K, calcitonin receptor, matrix metalloproteinase-9 expression and osteoclast-specific transcription factor, c-Fos, as well as osteotropic proinflammatory cytokine, TNF-alpha to a greater extent with DHA than EPA. Further, pretreatment of RAW 264.7 cells with DHA also showed significantly reduced activation of NF-kappaB and p38MAPK than EPA. Our findings suggest that DHA may be much more effective than EPA in alleviating RANKL induced proinflammatory cytokine production, intracellular signaling activation, thereby decreasing osteoclast activation and bone resorption.

Rahman MM, Bhattacharya A, Fernandes G
J. Cell. Physiol. Jan 2008
PMID: 17929247

DHA prevents, and GLA Exacerbates, Bone Loss in Ovariectomized Rats

Abstract

Specific effects of gamma-linolenic, eicosapentaenoic, and docosahexaenoic ethyl esters on bone post-ovariectomy in rats.

Long chain polyunsaturated fatty acids (LCPUFAs) are involved in the regulation of bone metabolism. Increased dietary consumption of n-3, and possibly some n-6, LCPUFAs may limit postmenopausal bone loss. The aim of this study was to determine the effects on bone of specific fatty acids within the n-3 and n-6 LCPUFA families in ovariectomized (OVX) rats. Rats were OVX or sham-operated and fed either a control diet (OVX and sham) or a diet supplemented with 0.5 g/kg body weight/day of gamma-linolenic (GLA), eicosapentaenoic (EPA), docosahexaenoic (DHA) ethyl esters or a mixture of all three (MIX) for 16 weeks. Bone mineral content (BMC), area, and density and plasma concentrations of insulin-like growth factor-I, vitamin D, selected biochemical markers of bone metabolism, and parathyroid hormone (PTH) were determined. The OVX-induced decrease in lumbar spine BMC was significantly attenuated by DHA but not by EPA or GLA supplementation or supplementation with a mixture of all three LCPUFAs. Endosteal circumferences of tibiae were significantly greater in DHA and EPA compared to OVX. Plasma C-terminal telopeptide of type I collagen and osteocalcin concentrations were not significantly different in the DHA group compared to OVX. Femur BMC decreased by a significantly greater amount in GLA than OVX, and final plasma PTH concentrations were significantly higher in GLA compared to all other groups. In conclusion, DHA ameliorated OVX-induced bone mineral loss. GLA exacerbated post-OVX bone mineral loss, possibly as a result of PTH-induced bone catabolism.

Poulsen RC, Firth EC, Rogers CW, Moughan PJ…
Calcif. Tissue Int. Dec 2007
PMID: 18008020

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

Fish May Protect Bone in Older Adults – 2011

Abstract

Protective effects of fish intake and interactive effects of long-chain polyunsaturated fatty acid intakes on hip bone mineral density in older adults: the Framingham Osteoporosis Study.

Polyunsaturated fatty acids and fish may influence bone health.
We aimed to examine associations between dietary polyunsaturated fatty acid and fish intakes and hip bone mineral density (BMD) at baseline (1988-1989; n = 854) and changes 4 y later in adults (n = 623) with a mean age of 75 y in the Framingham Osteoporosis Study.

BMD measures were regressed on energy-adjusted quartiles of fatty acid intakes [n-3 (omega-3): α-linolenic acid, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and EPA+ DHA; n-6 (omega-6): linoleic acid (LA) and arachidonic acid (AA); and n-6:n-3 ratio] and on categorized fish intakes, with adjustment for covariates. Effect modification by EPA+DHA intake was tested for n-6 exposures.
High intakes (≥3 servings/wk) of fish relative to lower intakes were associated with maintenance of femoral neck BMD (FN-BMD) in men (dark fish + tuna, dark fish, and tuna) and in women (dark fish) (P < 0.05). Significant interactions between AA and EPA+DHA intakes were observed cross-sectionally in women and longitudinally in men. In women with EPA+DHA intakes at or above the median, those with the highest AA intakes had a higher mean baseline FN-BMD than did those with the lowest intakes (quartile 4 compared with quartile 1: P = 0.03, P for trend = 0.02). In men with the lowest EPA+DHA intakes (quartile 1), those with the highest intakes of AA (quartile 4) lost more FN-BMD than did men with the lowest intakes of AA (quartile 1; P = 0.04). LA intake tended to be associated with FN-BMD loss in women (P for trend < 0.06).
Fish consumption may protect against bone loss. The protective effects of a high AA intake may be dependent on the amount of EPA+DHA intake.

Farina EK, Kiel DP, Roubenoff R, Schaefer EJ…
Am. J. Clin. Nutr. May 2011
PMID: 21367955 | Free Full Text

Fish Consumption Helps Maintain Bone in Spanish Women – 2013

Abstract

Dietary habits, nutrients and bone mass in Spanish premenopausal women: the contribution of fish to better bone health.

The moderate consumption of fish is recommended for a healthy diet and is also a feature of the Mediterranean diet. Fish is a major food group in diets throughout the world, and studies show that fish consumption is associated with a lower risk of a number of conditions. Spain has one of the highest annual per capita consumptions of fish worldwide. As fish is a source of high quality protein; n-3 polyunsaturated fatty acids; vitamins, such as A and D; and minerals, such as selenium, calcium, iodine, magnesium, copper and zinc, nutrients that have positive effects on bone characteristics, it has been proposed that its consumption could improve bone health. In this cross-sectional study, we have investigated the relationship between dietary habits and nutrient intake of 151 Spanish premenopausal women and analyzed the association of fish consumption on bone mass measured by quantitative ultrasound of the phalanges. A higher (P < 0.05) bone mass and vitamin D intake (P < 0.05) was observed in the group with a fish intake of 5-7 servings/week. We conclude that increased fish consumption is helpful in maintaining an adequate bone mass in Spanish premenopausal women.

Calderon-Garcia JF, Moran JM, Roncero-Martin R, Rey-Sanchez P…
Nutrients Jan 2013
PMID: 23271510 | Free Full Text

Vitamin D3 + K2 + Sr + Mg + DHA as Effective as Bisphosphonates in Women

Abstract

Combination of Micronutrients for Bone (COMB) Study: bone density after micronutrient intervention.

Along with other investigations, patients presenting to an environmental health clinic with various chronic conditions were assessed for bone health status. Individuals with compromised bone strength were educated about skeletal health issues and provided with therapeutic options for potential amelioration of their bone health. Patients who declined pharmacotherapy or who previously experienced failure of drug treatment were offered other options including supplemental micronutrients identified in the medical literature as sometimes having a positive impact on bone mineral density (BMD). After 12 months of consecutive supplemental micronutrient therapy with a combination that included vitamin D(3), vitamin K(2), strontium, magnesium and docosahexaenoic acid (DHA), repeat bone densitometry was performed. The results were analyzed in a group of compliant patients and demonstrate improved BMD in patients classified with normal, osteopenic and osteoporotic bone density. According to the results, this combined micronutrient supplementation regimen appears to be at least as effective as bisphosphonates or strontium ranelate in raising BMD levels in hip, spine, and femoral neck sites. No fractures occurred in the group taking the micronutrient protocol. This micronutrient regimen also appears to show efficacy in individuals where bisphosphonate therapy was previously unsuccessful in maintaining or raising BMD. Prospective clinical trials are required to confirm efficacy.

Genuis SJ, Bouchard TP
J Environ Public Health 2012
PMID: 22291722 | Free Full Text