High-Dose Eicosapentaenoic Acid and Docosahexaenoic Acid Supplementation Reduces Bone Resorption in Postmenopausal Breast Cancer Survivors on Aromatase Inhibitors: A Pilot Study

Abstract

Postmenopausal breast cancer survivors are living longer; however, a common class of drugs, aromatase inhibitors (AI), depletes estrogen levels, promotes bone loss, and heightens fracture risk. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may offset AI effects to bone because of the known effects on cellular processes of bone turnover. Therefore, we hypothesized that 4 g of EPA and DHA daily for 3 mo would decrease bone turnover in postmenopausal breast cancer survivors on AI therapy in a randomized, double-blind, placebo controlled pilot study that included 38 women. At baseline and 3 mo, serum fatty acids, bone turnover, and inflammatory markers were analyzed. Serum EPA and DHA, total and long-chain (LC) omega (n)-3 polyunsaturated fatty acids (PUFA) increased, whereas arachidonic acid, total and LC n-6 PUFA, and the LC n-6:n-3 PUFA ratio decreased compared to placebo (all P < .05). Bone resorption was inhibited in the fish oil responders compared to placebo (P < .05). Inflammatory markers were not altered. This short-term, high-dose fish oil supplementation study's findings demonstrate that fish oil can reduce bone resorption; however, longer-term studies are needed to assess bone density preservation and to explore mechanistic pathways in this population at high risk for bone loss.

Effects of ω3- and ω6-Polyunsaturated Fatty Acids on RANKL-Induced Osteoclast Differentiation of RAW264.7 Cells: A Comparative in Vitro Study

“…In line with this, research conducted by Sun et al (2003) reported the inhibitory effect of both EPA and DHA on osteoclastogenesis in bone marrow macrophages [33]. In a pilot study, Hutchins-Wiese et al (2014) showed that high-dose EPA and DHA supplementation reduced bone resorption in postmenopausal breast cancer survivors on aromatase inhibitors [34]. Increased dietary intake of AA has also been shown to lower the risk of hip fractures by 80% in men [35].…”

The Effect of Moderate Dietary Protein and Phosphate Restriction on Calcium‐Phosphate Homeostasis in Healthy Older Cats

“…The test diet was higher in ω‐3 PUFA than the control diet, which at high doses have renoprotective effects in experimental canine models of kidney disease, although it is not possible from this study to assess whether the increased concentration of ω‐3 PUFA had effects on the cats’ renal function. It is also possible that this difference could have had an impact on calcium‐phosphate homeostasis as there is emerging evidence that ω‐3 PUFA supplementation might reduce bone turnover in postmenopausal women . Markers of bone turnover were not examined in this study; however, ionized calcium concentrations increased more greatly in the test diet group, which could be a result of decreased calcium deposition in bone.…”

Palmitoleic Acid Inhibits RANKL-Induced Osteoclastogenesis and Bone Resorption by Suppressing NF-κB and MAPK Signalling Pathways

“…Similar to results on ω-3 LCPUFAs, we found that PLA inhibited NF-κB activity as well as the activation of the MAPKs, JNK and ERK. Supplementation with high doses of EPA and DHA has been shown to decrease bone loss associated with breast cancer [40]. Furthermore, diets rich in ω-3 LCPUFA have been associated with increased bone mineral density and peak bone mass [30].…”