Effect of n‐3 polyunsaturated fatty acid on bone health: A systematic review and meta‐analysis of randomized controlled trials

Abstract

Bone metabolism is a complicated process, which involves bone modeling and remodeling. If this process is unbalanced, bone loss and resultant osteoporosis might occur. Recently, nutrition supplementations such as n‐3 polyunsaturated fatty acids (PUFAs) are considered to be used on improving the bone metabolism and reducing the risk of osteoporosis. To more precisely assess the effects of n‐3 PUFA supplementation on bone mass and clarify its potential mechanism, we have conducted a systematic review and meta‐analysis. Based on the strict inclusion and exclusion criteria, 12 articles were included in this meta‐analysis. The results in articles show that n‐3 PUFAs could slightly enhance the level of bone mineral density (BMD) (0.005 g/cm2; 95% CI, 0.000–0.010) (n = 7), which was the primary outcome for the research in comparison with the control group. In addition, the results also illustrate that the increasing effect on BMD (0.024 g/cm2; 95% CI, 0.020–0.028) became more significant for postmenopausal women. N‐3 PUFAs had no significance on the level of bone‐specific alkaline phosphatase (BALP) (−0.24 µg/L; 95% CI, −0.86 to 0.39) and osteocalcin (−0.63 μg/L; 95% CI, −1.84 to 0.57) (n = 5), which are the specific markers of bone formation. When compared with the eicosapentaenoic acid + docosahexaenoic acid supplementation, the supplementation form of α‐linolenic acid significantly increased the content of BALP (0.396 µg/L; 95% CI, 0.069–0.724). The effects of n‐3 PUFAs on bone resorption biomarkers containing type I collagen cross‐linked C‐terminal peptide (CTX) and type I collagen cross‐linked N‐terminal peptide (NTX) are considered and used in our study. Results indicated that participants who received n‐3 PUFAs significantly decreased the level of CTX in the human body (−0.367 μg/L; 95% CI, −0.726 to −0.007) (n = 4). However, there was no significant difference in NTX levels in humans after supplementation with n‐3 PUFA (−1.744 µg/L; 95% CI, −3.970–0.481) (n = 3). For postmenopausal women, it presented a significant decreasing level of CTX (−0.393 µg/L; 95% CI, −0.651 to −0.135) and NTX (−2.082 µg/L; 95% CI, −2.970 to −1.195) within their bodies. In conclusion, these findings suggested that n‐3 PUFAs might have a beneficial effect on bone health, especially for α‐linolenic acid supplementation form or for postmenopausal women.

Causal effect of polyunsaturated fatty acids on bone mineral density and fracture

“…Recently, the relationship between PUFAs and osteoporosis has attracted a lot of attention. Some studies have found that intake of total PUFA, n-3 PUFAs, n-6 PUFAs can increase BMD and be beneficial to osteoporosis ( 30 – 34 ), which is mutually confirmed with our results.…”

“…PUFAs intake and the ratio of n-6 to n-3 PUFAs are reported to be associated with BMD in humans ( 27 , 30 – 32 ). Some studies found that total PUFAs, n-3 PUFAs, n-6 PUFAs intake can increase BMD, decrease the risk of fractures and beneficial for osteoporosis ( 30 – 34 ). A low n-6 to n-3 PUFAs ratio was proposed to be beneficial for the bone quality of rats ( 35 ).…”

Beneficial effects of monounsaturated fatty acid‐rich blended oils with an appropriate polyunsaturated/saturated fatty acid ratio and a low n‐6/n‐3 fatty acid ratio on the health of rats

“…Diets high in SFAs have been shown to have a detrimental effect on bone health 69 . Additionally, the plant n‐3 PUFA ALA has a protective effect in bone because it reduces bone resorption 70,71 . N‐3 PUFA has also been shown to improve trabecular and cortical structure, stiff bones and bone quality 72 .…”

“…69 Additionally, the plant n-3 PUFA ALA has a protective effect in bone because it reduces bone resorption. 70,71 N-3 PUFA has also been shown to improve trabecular and cortical structure, stiff bones and bone quality. 72 Finally, there is a correlation between the dietary n-6 and n-3 PUFA content and bone formation.…”

Relationship between diet-related inflammation and bone health under different levels of body mass index

“…The intake of pro-inflammatory diet may play an important role in bone heath. A number of recent systematic reviews and meta-analyses reported that dietary behaviors involving higher consumption of vitamin C, vitamin D, calcium, zinc and n-3 polyunsaturated fatty acid were linked with low incidence of bone loss [13][14][15]. Instead of focused on specific nutrients or dietary patterns, dietary inflammatory index (DII), a literature-based scoring algorithm based on the effort of 45 different food components on inflammatory biomarkers, was focused on quantitating the overall inflammatory potential of individual diets [16].…”