Table 3.
Randomised clinical trial results reporting the effect of soya isoflavone interventions and equol producer (EP) status on cholesterol and other lipid parameters*
| First author, year | CHD risk factor measured | Effect of isoflavone on CHD risk factors | Result marker† | Effect of EP status on CHD risk factors | Result marker‡ |
|---|---|---|---|---|---|
| Acharjee et al. (2015)(27) | TAG | Reduction in TAG in women with MetS (17·8 %, P = 0·04) after the soya intervention compared with placebo, unlike in women without MetS | + | Reduction in TAG in EP with MetS (22·9 %, P = 0·02) after the soya intervention compared with placebo. There were NS effects on NEP with or without MetS in TAG | + |
| Clerici et al. (2007)(56) | LDL-C, isoprostane excretion | Reduction in LDL-C (8·6 %, P = 0·002) compared with placebo after the soya intervention. Isoprostane excretion reduced from 58 (sem 6) ng/l at baseline to 39 (sem 4) ng/l after 4 weeks in the soya group (P < 0·001) (not measured in placebo group) | + | LDL-C reduced 15 (sem 7) mg/dl more in EP than in NEP (P = 0·042) after the soya intervention. Isoprostane excretion decreased in both EP and NEP, though more significantly in EP (P = 0·012) than NEP (P = 0·038) | + |
| Hall et al. (2006)(35) | %sdLDL-C | The isoflavone intervention was associated with a greater reduction of %sdLDL-C compared with placebo (24·14 (sd 14·26) and 22·22 (sd 11·87), respectively; P = 0·044) | + | The interaction between positive EP status and treatment was significant for %sdLDL-C (P < 0·05) | + |
| Hall et al. (2006)(35) | Lp(a) | The isoflavone intervention had a NS effect on Lp(a) compared with placebo | 0 | There was an interaction between EP status and treatment for Lp(a) (P < 0·05, data highly skewed) | + |
| Mangano et al. (2013)(42) | TC:HDL-C, LDL-C:HDL-C | The soya intervention had a NS effect on the risk factors compared with placebo | 0 | EP had lower TC:HDL and LDL-C:HDL-C compared with NEP (P = 0·018 and 0·043, respectively) after the isoflavone intervention | + |
| McVeigh et al. (2006)(67) | LDL-C | The soya intervention had a NS effect on LDL-C compared with placebo | 0 | EP status associated with a significant decrease in LDL-C on the low-isoflavone diet (P = 0·035) and high-isoflavone diet (P = 0·041) compared with placebo | + |
| Meyer et al. (2004)(59) | TC, LDL-C, LDL-C:HDL-C, TAG, Lp(a) | The soya intervention had a NS effect on the risk factors compared with placebo | 0 | EP status associated with significant reductions (P < 0·001) in TC (8·5 %), LDL-C (10 %), LDL-C:HDL-C ratio (13·5 %), TAG (21 %) and Lp(a) (11 %) after the soya intervention, unlike NEP | + |
| Pipe et al. (2009)(61) | TC, apoB | The isoflavone intervention had a NS effect on the risk factors compared with placebo | 0 | There was an interaction between EP status and TC (P = 0·05) and apoB (P = 0·04) after the soya intervention. There were NS effects of the soya intervention on TC or apoB in EP or NEP when analysed separately | + |
| Wong et al. (2012)(66) | HDL-C, apoA-I | The soya interventions had a NS effect on the risk factors compared with placebo | 0 | Apo A-I reduced in NEP but not EP (−0·08 (se 0·02) and −0·02 (se 0·02) g/l, respectively; P = 0·010) and HDL-C reduced in NEP but not EP (−0·07 (se 0·02) and 0·0 (se 0·03) mmol/l, respectively; P = 0·036) after the soya interventions | + |
| Badeau et al. (2007)(28) | Pre-(β) HDL-C | Pre-(β) HDL-C increased by 18 % (P < 0·05) after the isoflavone treatment | + | EP status had a NS effect on pre-(β) HDL-C levels after the isoflavone intervention | 0 |
| Clerici et al. (2007)(56) | TC | TC reduced after the soya intervention compared with placebo (7·3 %, P = 0·001) | + | TC reduction was greater in EP than NEP (P = 0·103) after the soya intervention | 0 |
| Gardner et al. (2007)(57) | LDL-C | LDL-C decreased after both soya interventions compared with placebo (161 (sd 20), 161 (sd 26), and 170 (sd 24) mg/dl for the WB soya milk, SPI milk, and dairy milk, respectively; P = 0·02 for each soya milk v. dairy milk) | + | EP status had a NS effect on LDL-C after either soya milk intervention | 0 |
| Greany et al. (2004)(32) | TC, LDL-C, HDL-C, TAG | Reductions in TC (−2·2 %, P = 0·02), LDL-C (−3·5 %, P = 0·006) and TAG (−8·8 %, P = 0·07) while HDL-C increased (4·2 %, P = 0·006) after the soya intervention compared with control | + | EP status had a NS effect on the risk factors on in all subjects, hypercholesterolaemic subjects alone, or normocholesterolaemic subjects alone after the soya intervention | 0 |
| McVeigh et al. (2006)(67) | TC:HDL-C, LDL-C:HDL-C, apoB:apoA-I | Reductions in TC:HDL-C, LDL-C:HDL-C, apoB:apoA-I after the soya diets (P = 0·031, 0·006, 0·011, respectively in the low-soya diet, P = 0·054, 0·012, 0·005, respectively in the high-soya diet) compared with control | + | Interaction of EP status and treatment was NS for the risk factors | 0 |
| Nestel et al. (2004)(60) | LDL-C | LDL-C reduced after the genistein-rich (biochanin) isoflavone intervention compared with placebo (P = 0·026) | + | EP status had a NS effect on LDL-C after the isoflavone interventions | 0 |
| Pipe et al. (2009)(61) | LDL-C, LDL-C:HDL-C, apoB:apoA-I | Reductions in LDL-C (P = 0·04), LDL-C:HDL-C (P = 0·04), and apoB:apoA-I (P = 0·05) after the isoflavone intervention compared with placebo | + | EP status had a NS effect on the risk factors after the isoflavone intervention | 0 |
| Qin et al. (2014)(62) | TAG | Reduction in the low- and high-daidzein interventions compared with placebo in TAG (−0·15 (sd 0·062) and 0·24 (sd 0·61) mmol/l, respectively; P < 0·05) | + | EP status had a NS effect on TAG after the isoflavone intervention | 0 |
| Thorp et al. (2008)(64) | TC, TAG | The soya diet caused a 3 % greater reduction in TC (−0·17 (sem 0·06) mmol/l, P < 0·05) and 4 % greater reduction in TAG (−0·14 (sem 0·05) mmol/l; P < 0·05) compared with control | + | NS interaction between EP status and diet treatment on the risk factors (P > 0·68 for all). | 0 |
| Wong et al. (2012)(66) | LDL-C, apoB | Reductions in LDL-C and apoB after the soya treatments compared with placebo (P values not provided) | + | EP status had a NS effect on the risk factors after the soya treatments | 0 |
| Acharjee et al. (2015)(27) | TC, LDL-C, HDL-C | The soya intervention had a NS effect on the risk factors compared with placebo | 0 | EP status had a NS effect on the risk factors compared with placebo | 0 |
| Badeau et al. (2007)(28) | ABCA1-dependent cholesterol efflux, TC, HDL-C, HDL-2, HDL-3, TC:HDL-C, non-HDL-C, TAG, apoA-I | The isoflavone intervention had a NS effect on the risk factors compared with placebo | 0 | EP status had a NS effect on the lipid risk factors. ABCA1-dependent cholesterol efflux values were higher in EP than NEP (3·4 (sd 1·4) % and 2·7 (sd 0·6) %, respectively), though NS, after the isoflavone intervention | 0 |
| Gallagher et al. (2004)(31) | TC, LDL-C, HDL-C, TAG, apoA-I, apoB | The soya intervention had a NS effect on the risk factors compared with placebo | 0 | NS differences in percentage change between equol levels and the risk factors after the isoflavone intervention | 0 |
| Hall et al. (2006)(35) | TC, LDL-C, HDL-C, TAG, TC:HDL-C | The isoflavone intervention had a NS effect on the risk factors compared with placebo | 0 | EP status had a NS effect on the risk factors after the isoflavone intervention | 0 |
| Kreijkamp-Kaspers et al. (2004)(38) | TC, HDL-C, LDL-C, TAG, Lp(a) | The soya intervention had a NS effect on the risk factors compared with placebo | 0 | NS interaction with EP status and any of the risk factors | 0 |
| Ma et al. (2005)(58) | TC, HDL-C, LDL-C, TAG | The isoflavone intervention had a NS effect on the risk factors compared with placebo | 0 | EP status had a NS effect on the risk factors after the isoflavone intervention | 0 |
| Mangano et al. (2013)(42) | TC, HDL-C, LDL-C, TAG | The soya intervention had a NS effect on the risk factors compared with placebo | 0 | EP status had a NS effect on the risk factors after the soya intervention | 0 |
| McVeigh et al. (2006)(67) | TC, HDL-C, non-HDL-C, TAG, apoA-I, apoB | The soya intervention had a NS effect on the risk factors compared with placebo | 0 | NS interaction with EP status and the soya intervention and any of the risk factors | 0 |
| Meyer et al. (2004)(59) | HDL-C | The soya intervention had a NS effect on HDL-C compared with placebo | 0 | EP status had a NS effect on HDL-C after the soya intervention | 0 |
| Nestel et al. (2004)(60) | LDL-C | The intervention of isoflavones isolated from red clover enriched in formononetin had a NS effect on LDL-C compared with placebo | 0 | EP status had a NS effect on LDL-C after the isoflavone treatments | 0 |
| Nikander et al. (2004)(43) | TC, LDL-C, HDL-C, TAG, apoA-I, apoB, Lp(a) | The isoflavonoid intervention had a NS effect on the risk factors compared with placebo though in women with baseline levels of LDL-C above the median LDL-C, it increased (P = 0·009) | 0 | EP status had a NS effect on the risk factors after the isoflavonoid intervention | 0 |
| Pipe et al. (2009)(61) | HDL-C, non-HDL-C, TAG, apoA-I, TC: HDL-C, TAG:HDL-C, non-HDL:HDL-C | The isoflavone intervention had a NS effect on the risk factors compared with placebo | 0 | EP status had a NS effect on the risk factors after the isoflavone intervention | 0 |
| Qin et al. (2014)(62) | HDL-C, LDL-C, apoA-I, apoB, Lp(a) | The isoflavone intervention had a NS effect on the risk factors compared with placebo | 0 | EP status had a NS effect on the risk factors after the isoflavone intervention | 0 |
| Reverri et al. (2015)(63) | OxLDL-C | The soya intervention had a NS effect on oxLDL-C compared with placebo | 0 | EP status had a NS effect on oxLDL-C after the soya intervention | 0 |
| Steinberg et al. (2003)(48) | TC, LDL-C, HDL-C, TC:HDL-C, TAG, CD formation | The isoflavone intervention had a NS effect on the risk factors | 0 | EP status had a NS effect on the risk factors after the soya interventions | 0 |
| Thorp et al. (2008)(64) | LDL-C, HDL-C, TC:HDL-C | The soya intervention had a NS effect on the risk factors | 0 | NS interaction between EP status and diet treatment on the risk factors after the soya intervention (P > 0·68 for all) | 0 |
| Törmälä et al. (2006)(52) | TC, HDL-C, LDL-C, TAG, apoA-I, apoB, serum cholesterol efflux capacity | The isoflavone intervention had a NS effect on the risk factors compared with placebo | 0 | EP status had a NS effect on the risk factors after the isoflavone intervention | 0 |
| West et al. (2005)(65) | TC, HDL-C, LDL-C, apoA-I, apoB, Lp(a) | The soya intervention had a NS effect on the risk factors compared with placebo | 0 | EP status had a NS effect on the risk factors after the soya intervention | 0 |
| Wong et al. (2012)(66) | TC, TC:HDL-C, LDL-C:HDL-C, TAG, apoB:apoA-I | The soya interventions had a NS effect on the risk factors on the risk factors compared with placebo | 0 | EP status had a NS effect on the risk factors after the soya treatments | 0 |
| Sen et al. (2012)(47) | Isoprostane excretion | There was a positive association between isoprostane excretion and isoflavones after the high soya diet intervention (P = 0·02) | – | There was a positive association between isoprostane excretion and the isoflavone intervention for EP (P = 0·03) but not NEP (P = 0·32) after the high-soya diet intervention | – |
MetS, metabolic syndrome; NEP, non-equol producer; LDL-C, LDL-cholesterol; sdLDL-C, small dense LDL-C; Lp, lipoprotein; TC, total cholesterol; HDL-C, HDL-cholesterol; WB, whole bean soya; SPI, soya protein isolate; ABCA1, adenosine triphosphate-binding cassette A1; CD, conjugated diene formation; OxLDL-C, oxidised LDL-C.
*
Results are first stratified by the impact of EP status and then the impact of the soya isoflavone interventions on each of the lipid risk factors.
†
+, Beneficial effect of soya isoflavones on risk factors of CHD; 0, negligible effect of soya isoflavones on risk factors of CHD; –, adverse effect of soya isoflavones on risk factors of CHD.
‡
+, Beneficial effect of EP status on risk factors of CHD after soya intervention; 0, negligible effect of EP status on CHD risk factors after soya intervention; –, adverse effect of EP status on risk factors of CHD after soya intervention.