Table 2.
Summary of randomized controlled trials included in systematic review organized by primary outcome measures
| Author | Patient/subjects | n | Study Design | Outcome Measures* | Effect Size (95% CI) |
Quality of Evidence |
Conclusions | |
|---|---|---|---|---|---|---|---|---|
| Studies with Bone Mineral Density as Primary Outcome | ||||||||
| Cornish and Chili-beck 2009 | Older healthy adults (65·4 ± 0·8 yrs Canadian, 28M, 23F) | 51 | Double blinded randomized 30ml flaxseed oil (14 g ALA, n 25) vs corn oil placebo (n 26) plus resistance training for 12 wks | Primary | Lumber BMD | 0·1 (−0·45,0·64) | low1 | No significant difference |
| Hip BMD | 0 (−0·55,0·55) | |||||||
| Dodin et al., 2005 | Postmenopausal women in Canada | 179 | Double blinded randomized 40 g/day flaxseed (n 85) vs wheat germ placebo (n 94) for 1 yr | Primary | Lumbar BMD | 0·22 (−0·07,0·52) | mod2 | No significant differences |
| Femoral neck BMD | 0·23 (−0·06,0·53) | |||||||
| Kruger et al., 1998 | Postmenopausal women with senile osteoporosis (mean age 79·5 years) in S. Africa | 60 | Randomized evening primrose oil + fish oil + calcium (n 29) vs coconut oil + calcium placebo (n 31) for 18 months | Primary | Lumbar BMD | 0·75 (0·22,1·27) | mod3 | A combination of GLA, EPA, DHA, LA and calcium may maintain lumbar and increase femoral neck BMD compared to coconut oil and calcium |
| Femoral neck BMD | 2·16 (1·52,2·79) | |||||||
| Secondary | OC | −0·14 (−0·64,0·37) | ||||||
| BSAP | 0·04 (−0·47,0·54) | |||||||
| Dpyr | 0·29 (−0·22,0·79) | |||||||
| Bassey et al., 2000 | Healthy premenopausal women (34–35 yr) in UK | 43 | Double blinded randomized Efacal (4 g evening primrose oil, 440mg fish oil, 1 g calcium; n 19) vs 1 g calcium control (n 24) for 1 yr | Primary | Total BMD | −0·34 (−0·94,0·27) | low4 | No significant differences |
| Secondary | OC | 0 (−0·61,0·6) | ||||||
| NTX | −0·12 (−0·72,0·48) | |||||||
| BSAP | 0·26 (−0·35,0·86) | |||||||
| Healthy postmenopausal women (55–58 yr) in UK | 45 | Double blinded randomized Efacal (n 21) vs calcium control (n 24) for 1 yr | Primary | Total BMD | 0·42 (−0·19,1·03) | low4 | No significant differences | |
| Secondary | OC | −0·52 (−1·13,0·1) | ||||||
| NTX | −0·26 (−0·87,0·35) | |||||||
| BSAP | 0·04 (−0·57,0·64) | |||||||
| Studies with Bone Formation/Resorption Markers as Primary Outcome | ||||||||
| Appleton et al., 2011 | Mild-moderately depressed adults (total 190, only 113 in the analysis, 26M, 87F) in UK | 113 | Double blinded, randomized to 1·48 g EPA + DHA (n 53) vs olive oil placebo (n 60) for 12 wks | Ancillary data analysis | Serum β-CTX | 0·05 (−0·32,0·42) | low5 | No significant differences |
| Salari et al., 2010 | Postmenopausal women in Iran | 25 | Blinded, randomized to 900mg omega 3 FA (n 13) vs unidentified placebo (n 12) for 6 months | Primary | Serum OC** | 0·22 (−0·56,1·01) | very low6 | No significant differences |
| Serum BSAP** | −0·37 (−1·17,0·42) | |||||||
| uPyr** | 0·32 (−0·47,1·11) | |||||||
| Dawczynski et al., 2009 | Rheumatoid arthritis patients in Germany (43F, 2M) | 45 | Double blinded, randomized crossover design omega 3 fortified dairy (1·1 g ALA, 0·7 g EPA, 0·4 g DHA) vs standard dairy products in diet for 12 wks and 8 wks washout | One of Primary endpoints | Pyr/Cr | 0·35 (−0·26,0·96) | low7 | Dairy products fortified with ALA, EPA and DHA may decrease a urinary marker of bone resorption compared to standard dairy products |
| Dpyr/Cr | 0·89 (0·25,1·52) | |||||||
| Griel et al., 2007 | Hyperlipidemic adults (48·6 ± 1·6 year, 20M, 3F) in US | 23 | Double blinded, randomized three period crossover design Average American, LA, ALA diet with 6 wk diet, ~3 wk washout | Ancillary data analysis | NTX | 1·94 (1·24,2·64) | mod8 | A high ALA diet may decrease a marker of bone resorption compared to average American diet |
| BSAP | 0·2 (−0·38,0·77) | |||||||
| Studies with Regulators of Bone Turnover as Primary Outcome | ||||||||
| Martin-Bautista et al., 2010 | Hyperlipidemic patients in Spain (35–65y) | 72 | Double blinded randomized to fortified milk with fish oil (0·06 g ALA, 0·2 g EPA, 0·14 g DHA) oleic acid and vitamins (n 39) vs standard milk control (n 33) for 1 yr | Ancillary data analysis | OPG | 2·92 (2·26,3·59) | mod9 | Milk fortified with fish oil, oleic acid and vitamins may improve regulators of bone turnover compared to standard milk |
| RANKL | 0·71 (0·23,1·19) | |||||||
| OPG/RANKL | 0·27 (−0·2,0·74) | |||||||
| OC | 4·34 (3·5,5·19) | |||||||
| CTX | 0·03 (−0·43,0·5) | |||||||
| Kolahi et al., 2010 | Women with rheumatoid arthritis (18–74 yr, mean 50) in Iran | 83 | Double blinded randomized, fish oil (1 g/d, n 40) vs placebo (n 43) for 6 months | Primary | OPG | Insufficient data for ES calculation | very low10 | Authors reported significant increase in OPG and decrease in sRANKL |
| RANKL | ||||||||
BMD - Bone mineral density; OC - Osteocalcin; BSAP - Bone specific alkaline phosphatase; Dpyr - deoxypyridinoline; uPyr - urinary pyridinoline; NTX- N-terminal telopeptide; CTX - C-terminal telopeptide; Cr - Creatinine; OPG - osteoprotegerin; RANKL-receptor activator of nuclear factor κβ
The effect sizes for these measures were based on the data estimated from the figures in the paper.
No intention to treat analysis, indirect evidence regarding effect of ALA related to resistance training, short duration of treatment for endpoint measured.
Indirect evidence regarding effect of ALA related to multiple components of flaxseed and wheat germ.
Unclear if double blinded, indirect evidence regarding EPA + DHA related to multiple components of supplement.
Large loss to follow up, small sample size in each age category, no intention to treat analysis.
Large loss to follow up and/or exclusion, no intention to treat analysis, only one secondary endpoint measure, ancillary data analysis.
Large loss to follow up, small sample size, unclear if double blinded, placebo not identified.
Large loss to follow up and/or exclusion, no intention to treat analysis, small sample size, indirect evidence regarding effect of ALA, EPA + DHA related to multiple components of fortified foods.
Small sample size, ancillary data analysis.
Moderate sample size, ancillary data analysis, indirect evidence regarding effect of EPA + DHA related to multiple components of fortified food.
Insufficient data to calculate effect size, placebo not identified, wide standard deviations of endpoint measures, incomplete description of statistical methods.