Nutrients, 2017, Volume 24; Issue 9: Page 10. pii: E1162. doi: 10.3390/nu9101162.

Effect of Altering Dietary n-6:n-3 Polyunsaturated Fatty Acid Ratio with Plant and Marine-Based Supplement on Biomarkers of Bone Turnover in Healthy Adults.

Rajaram, S. Yip, EL. Reghunathan, R. Mohan, S. Sabate, J.

Key Findings

n-3 PUFAs may play an important role in bone metabolism and may represent a potentially useful non-pharmacological therapeutic strategy to prevent bone loss and reduce the risk of osteoporosis. A lower ratio of n-6:n-3 PUFA shows a positive influence on bone. Typical Western diets are associated with higher n-6:n-3 PUFA ratios, whereas, it is the low n-6:n-3 ratios that are correlated with optimal health and decreased risk of disease. The objective of this study was to examine the effect of altering the dietary n-6:n-3 PUFA ratio from 10:1 to 2:1 with and without adding a supplement of EPA/DHA.  The study showed that altering the n-6:n-3 fatty acid ratio from 10:1 to 2:1 by increasing ALA (8.6 g of ALA) or by adding a supplement (1 g EPA + DHA/day) to either the 10:1 or 2:1 diet in the short term (eight weeks) did not alter serum bone markers or PPAR-γ gene expression in healthy adults. While these amounts promote cardioprotective effects, it appears that this dose may not be sufficient to influence bone turnover in healthy subjects. Lack of results from this cohort may be partly due to a lower ALA intake even in 2:1 diet groups. Alternatively, the duration of intervention may have been too short to see changes in bone turnover markers in a relatively young, healthy adult cohort.   The bone-protective effects observed with a low dietary n-6:n-3 ratio may be attributed to a lower concentration of eicosanoids arising from the n-6 fatty acids pathway This study observed a significant negative association between serum CTX and RBC membrane LA and ALA. Although the RBC ALA levels increased both by increasing ALA (2:1 diet) and by adding a supplement (10:1 + S and 2:1 + S diets) in this study, it is likely that it was insufficient to modify PGE2 or other inflammatory markers. Perhaps individuals with elevated inflammation at baseline may better respond to n-3 PUFA with respect to markers of bone formation and resorption.   Epidemiological and intervention studies have shown that increasing n-3 PUFAs (ALA, EPA/DHA) and/or lowering the dietary n-6:n-3 PUFA ratio may have bone protective effects. However, this study on healthy adults did not show any change in bone formation or resorption markers, even when the dietary n-6:n-3 PUFA ratio was altered from 10:1 to 2:1 using ALA-rich food sources or when a supplement containing EPA/DHA was added to the two diets. A low rate of bone turnover in these relatively young and healthy adults may be one of the reasons for the lack of favorable results. There is still merit to exploring the role of n-3 fatty acids on bone metabolism since these fatty acids clearly play a role in bone remodeling and bone microstructure. This study showed that incorporating plant sources of n-3 PUFA (ALA) can help reduce the dietary n-6:n-3 PUFA ratio and increase RBC EPA levels significantly. Whether or not these translate to protective effects on the bone metabolism of healthy adults’ remains to be further explored.


Although there is accumulating evidence for a protective role of n-3 polyunsaturated fatty acids (n-3 PUFAs) on bone health, there are limited studies that examine the effect of altering dietary n-6:n-3 PUFA ratio with plant and marine sources of n-3 PUFA on bone health. Healthy adults (n = 24) were randomized into an eight-week crossover study with a four-week washout between treatments, with each subject consuming three of four diets. The four diets differed in the dietary n-6:n-3 PUFA ratios and either had an algal oil supplement added or not: (Control diet (10:1); α-linolenic acid (ALA) diet (2:1); Eicosapentaenoic acid/Docosahexaenoic acid (EPA/DHA) diet (10:1 plus supplement (S) containing EPA/DHA; Combination diet (2:1 + S)). The supplement was microalgae oil that provided 1 g EPA + DHA/day. Flaxseed oil and walnuts provided 8.6 g of ALA/day in the 2:1 diets. Serum levels of c-telopeptide (CTX), procollagen Type I N-terminal peptide, and osteocalcin showed significant correlation with age but none of the bone markers or peroxisomal proliferator-activated receptor-γ mRNA expression was significantly different between the diets. Serum CTX was negatively associated with red blood cell membrane linoleic acid and ALA and positively associated with membrane DHA. Neither altering dietary n-6:n-3 PUFA ratio from a 10:1 to a 2:1 ratio nor adding EPA/DHA supplement significantly changed bone turnover in the short term in healthy adults.

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