Journal Name:
J. Nutr.
Article Title:
An increase in dietary n-3 fatty acids decreases a marker of bone resorption in Humans
Date Written:
2007
Volume:
6
Number:
2
Page:
1
Author(s):
Griel, A.E.; Kris-Etherton, P.M.; Hilpert, K.F.; Zhao, G.; West, S.G.; Corwin, R.L.
Article:
Human, animal, and in vitro research indicates a beneficial effect of omega-3 (n-3) polyunsaturated fatty acids (PUFA) on bone health. This is the first controlled feeding study in humans to evaluate the effect of dietary plant-derived n-3 PUFA (alpha linolenic acid – ALA) on bone turnover, assessed by serum concentrations of N-telopeptides (NTx) and bone-specific alkaline phosphatase (BSAP). In this metabolic feeding trial, subjects (n=23) consumed each diet for 6 weeks in a randomized, 3-period crossover design: 1) Average American Diet (AAD; [34% total fat, 13% saturated fatty acids (SFA), 13% monounsaturated fatty acids (MUFA), 9% PUFA (7.7% LA, 0.8% ALA)]), 2) Linoleic Acid Diet (LA; [37% total fat, 9% SFA, 12% MUFA, 16% PUFA (12.6% LA, 3.6% ALA)]), and 3) ALA Diet (ALA; [38% total fat, 8% SFA, 12% MUFA, 17% PUFA (10.5% LA, 6.5% ALA)]). Walnuts and flaxseed oil were the predominant sources of ALA.
NTx levels were significantly lower following the ALA diet (13.20 + 1.21 nM BCE), relative to the AAD (15.59 + 1.21 nM BCE). Mean NTx level following the LA diet was 13.80 + 1.21 nM BCE. There was no change in levels of BSAP across the three diets.
Concentrations of NTx were positively correlated with the pro-inflammatory cytokine TNF-alpha for all three diets. The results indicate that ALA may have a protective effect on bone metabolism via a decrease in bone resorption in the presence of consistent levels of bone formation. These effects are consistent with a reduction in bone turnover and maintenance of bone formation induced by relatively short-term consumption of the high ALA diet.
Although the effects of dietary fats on bone health have been studied in animals and through supplementation in humans, this is the first study to use a whole food source, incorporated into the diet of humans under controlled feeding conditions. Previous studies have shown beneficial effects of ALA on CVD risk; the present results indicate potential benefits on bone health, as well.
The changes in n-6/n-3 ratios in the present study were accomplished by increasing the n-3 PUFA, while maintaining relatively constant levels of n-6 PUFA. NTx levels were significantly lower when subjects consumed the ALA diet (n-6/n-3 ratio: 1.6) than when they consumed the AAD (n-6/n-3 ratio: 9.5); when subjects consumed the LA diet (n-6/n-3 ratio: 3.5), NTx levels were marginally significantly lower than when they consumed the AAD (p=0.08). This stepwise reduction in NTx across the three diets (ALA < LA < AAD) indicates a possible dose response effect of dietary n-3 fatty acids and/or reductions in the n-6/n-3 ratio on bone resorption. The stepwise nature of the results also indicates that the reductions in NTx were not due simply to the lower dietary SFA or the elevated LA in the LA and ALA diets.
The present findings confirm and extend a growing literature indicating beneficial effects of ALA and reduced n-6/n-3 ratios on bone health. The present results are consistent with animal work in which appropriate amounts of n-3 PUFA reduced osteoclast activity. One mechanism that might account for this involves local alterations of fatty acid and prostaglandin concentrations within bone tissue. Increased consumption of n-6 PUFA increases the ratio of arachidonic acid (AA) to EPA, and increases PGE2 concentration in bone. Conversely, an increased consumption of n-3 PUFA decreases the AA:EPA ratio, and decreases PGE2, concentration and release from bone. This cascade of effects is potentially important, as PGE2 has been reported to stimulate bone resorption. EPA serves as a precursor for the formation of PGE3, which also can stimulate bone resorption.
TNF-α levels were correlated with NTx levels across all of the diets. TNF-α promotes osteoclastic bone resorption and inhibits bone collagen synthesis in vitro, effects that may be mediated by PGE2. In a previous study by the same authors, supplementation with ALA reduced systemic TNF-α by about 30% in humans, as well as in wild-type and IL-10 knockout mice, and increased bone mineral content in IL-10 knockout mice. Systemic TNF-α therefore, may be an important marker of, and/or contributor to, bone resorptive mechanisms.
Taken together, the present results are consistent with literature indicating that dietary ALA can reduce bone resorption possibly through reduced production of TNF-α.
In summary, the results of the present study indicate that incorporating ALA into the diet with a decrease the n-6/n-3 ratio reduces serum NTx and maintains levels of serum BSAP. The reductions in NTx were related to the amount of ALA each diet provided. Omega-3 fatty acids are known to have beneficial effects on the cardiovascular system, but few studies have examined their effects on human bone health. The present results suggest that incorporating plant sources of n-3 PUFA into the diet may provide health benefits not only to the cardiovascular system, but also to the skeletal system.
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