Lipid lowering nutraceuticals in clinical practice: position paper from an International Lipid Expert Panel

In the paper

“Then, the improvement of lipid profile was not dependent on duration of supplementation or baseline lipid levels”

What the sources say

• Not checked yetcites [244] Pirro M Mannarino MR Ministrini S Effects of a nutraceutical combination on lipids, inflammation and endothelial integrity in patients with subclinical inflammation: a randomized clinical trial Sci Rep 2016 6 23587 27004462 PMC4804276

In the paper

“This combination has also been tested in adult and elderly patients previously intolerant to statins [245, 246], being well tolerated in 80% of cases.”

What the sources say

• Not checked yetcites [245] Marazzi G Cacciotti L Pelliccia F Long-term effects of nutraceuticals (berberine, red yeast rice, policosanol) in elderly hypercholesterolemic patients Adv Ther 2011 28 1105 13 22113535
• Not checked yetcites [246] Cicero AF Derosa G Borghi C Red yeast rice and statin-intolerant patients Am J Cardiol 2010 105 1504 20451704

In the paper

“The association of the lipid-lowering properties of red yeast rice (3 mg MonK), policosanols (10 mg) and berberine (500 mg) is the most studied in RCTs and the only one for which meta-analyses of RCTs are available.”

In the paper

“It was highlighted that LDL-C change was positively associated with hs-CRP (p = 0.04) and endothelial microparticle changes (p < 0.001)”

What the sources say

• Not checked yetcites [244] Pirro M Mannarino MR Ministrini S Effects of a nutraceutical combination on lipids, inflammation and endothelial integrity in patients with subclinical inflammation: a randomized clinical trial Sci Rep 2016 6 23587 27004462 PMC4804276

In the paper

“hs-CRP and endothelial microparticle levels were also significantly decreased (–41% and –16%, respectively)”

What the sources say

• Not checked yetcites [244] Pirro M Mannarino MR Ministrini S Effects of a nutraceutical combination on lipids, inflammation and endothelial integrity in patients with subclinical inflammation: a randomized clinical trial Sci Rep 2016 6 23587 27004462 PMC4804276

In the paper

“while a greater glucose-lowering effect was found with higher baseline glucose levels and longer durations of supplementation [244]”

What the sources say

• Not checked yetcites [244] Pirro M Mannarino MR Ministrini S Effects of a nutraceutical combination on lipids, inflammation and endothelial integrity in patients with subclinical inflammation: a randomized clinical trial Sci Rep 2016 6 23587 27004462 PMC4804276

In the paper

“In the available studies none of the participants reported any muscle pains and no abnormal liver function tests were observed while taking this supplement.”

In the paper

“the authors observed a reduction of LDL-C by 14.3% (–0.57 mmol/l (22 mg/dl), 95% CI: –0.8; –0.31), as well as TC, apoB100 and apoB100/apoA-I ratio, without modifying safety parameters [254].”

What the sources say

• Not checked yetcites [254] Barrat E Zaïr Y Ogier N A combined natural supplement lowers LDL cholesterol in subjects with moderate untreated hypercholesterolemia: a randomized placebo-controlled trial Int J Food Sci Nutr 2013 64 882 9 23815518

In the paper

“After 8 weeks of treatment, the results showed a significant decrease in LDL-C (–0.97 ±0.35 mmol/l (37.5 mg/dl); –22 ±3%), TG (–0.22 ±0.28 mmol/l (19.5 mg/dl); –9 ±5%) and non-HDL-C (–21 ±3%) and a significant increase in HDL-C (+1.5 ±0.5%) (p < 0.001 for all), without the modification of safety parameters.”

What the sources say

• Not checked yetcites [267] Cicero AF Derosa G Pisciotta L Barbagallo C SISA-PUFACOL Study Group Testing the short-term efficacy of a lipid-lowering nutraceutical in the setting of clinical practice: a multicenter study J Med Food 2015 18 1270 3 26274827 PMC4638196

In the paper

“Based on the available data, no serious safety concerns have been raised, but further studies with longer follow-up are necessary to conclusively confirm this.”

In the paper

“After 3 months of treatment, the nutraceutical supplement decreased LDL-C compared to baseline (p = 0.041) and to placebo (p = 0.037, respectively).”

What the sources say

• Not checked yetcites [257] Derosa G Bonaventura A Bianchi L A randomized, placebo-controlled study on the effects of a nutraceutical combination of red yeast rice, silybum marianum and octasonol on lipid profile, endothelial and inflammatory parameters J Biol Regul Homeost Agents 2014 28 317 24 25001663

In the paper

“Triglycerides were reduced by the active product (p = 0.039), but not by the placebo, even though, in the group-to-group comparison, no significant difference was recorded (p = 0.061).”

What the sources say

• Not checked yetcites [257] Derosa G Bonaventura A Bianchi L A randomized, placebo-controlled study on the effects of a nutraceutical combination of red yeast rice, silybum marianum and octasonol on lipid profile, endothelial and inflammatory parameters J Biol Regul Homeost Agents 2014 28 317 24 25001663

In the paper

“after 16 weeks of treatment, LDL-C was reduced by 21.4% (95% CI: –13.3; –24.9%, p < 0.001), while TG decreased by 12.2% (95% CI: –24.4; –0.1%, p < 0.05) [253].”

What the sources say

• Not checked yetcites [253] Ogier N Amiot MJ Georgé S LDL-cholesterol-lowering effect of a dietary supplement with plant extracts in subjects with moderate hypercholesterolemia Eur J Nutr 2013 52 547 57 22527287

In the paper

“No safety concerns. Very limited data; further studies are necessary.”

In the paper

“Based on the available data, no serious safety concerns have been raised.”

In the paper

“An improvement of lipid parameters was assessed after the treatment (LDL-C 2.9 ±0.2 mmol/l (112 mg/dl) vs. control group 3.6 ±0.2 mmol/l (140 mg/dl), p < 0.05). Plasma lathosterol concentrations, an index of cholesterol biosynthesis, were lowered after the combination treatment (p < 0.05), as well [274].”

What the sources say

• Not checked yetcites [274] Yoshida M Vanstone CA Parsons WD Zawistowski J Jones PJ Effect of plant sterols and glucomannan on lipids in individuals with and without type II diabetes Eur J Clin Nutr 2006 60 529 37 16391591

In the paper

“after their intake for 4 weeks, there was reported a reduction of LDL-C of 35.0 ±3.1% (p < 0.001), and the ratio of LDL-C to HDL-C (30.0 ±3.5%, p < 0.001) [266].”

What the sources say

• Not checked yetcites [266] Jenkins DJ Kendall CW Marchie A The effect of combining plant sterols, soy protein, viscous fibers, and almonds in treating hypercholesterolemia Metabolism 2003 52 1478 83 14624410

In the paper

“No safety concerns. Very limited data; further studies are necessary.”

In the paper

“When compared to placebo, nutraceutical combination treated patients experienced a more favorable percentage change in LDL-C (–23.3%), hs-CRP (–2.4%), and endothelial function (pulse volume displacement vs. baseline: +17%).”

What the sources say

• Not checked yetcites [258] Cicero AF Colletti A Rosticci M Grandi E Borghi C Efficacy and tolerability of a combined lipid-lowering nutraceutical on cholesterolemia, hs-CRP level and endothelial function in moderately hypercholesterolemic subjects J Biol Regul Homeost Agents 2016 30 593 8 27358154

In the paper

“No safety concerns. Very limited data; further studies are necessary.”

In the paper

“No safety concerns. Very limited data; further studies are necessary.”

In the paper

“After 2 months of treatment, there was a significant reduction of LDL-C by 14% (p < 0.003), VLDL dropped by 20% (p < 0.01) and sdLDL particles fell by 25% (type III and IV) [275].”

What the sources say

• Not checked yetcites [275] Houston M Sparks W Effect of combination pantethine, plant sterols, green tea extract, delta-tocotrienol and phytolens on lipid profiles in patients with hyperlipidemia JANA 2010 13 15 20

In the paper

“Based on the available data, no safety concerns have been raised, but further studies with a long follow-up are still necessary to confirm this.”

In the paper

“No safety concerns. Very limited data; further studies are necessary.”

In the paper

“When compared to the placebo group, monacolins/CoQ10-treated patients experienced a more favorable percent change in LDL-C (–21.99%, 95% CI: –26.63; –17.36), non-HDL-C (–14.67%, 95% CI: –19.22; –10.11), MMP-2 (–28.05%, 95% CI: –35.18; –20.93), MMP-9 (–27.19%, 95% CI: –36.21; –18.15), and hs-CRP (–23.77%, 95% CI: –30.54; –17.01).”

What the sources say

• Not checked yetcites [259] Cicero AF Derosa G Parini A Red yeast rice improves lipid pattern, high-sensitivity C-reactive protein, and vascular remodeling parameters in moderately hypercholesterolemic Italian subjects Nutr Res 2013 33 622 8 23890351

In the paper

“LDL-C decreased significantly after the treatment (3.4 ±0.7 (131 mg/dl) to 2.7 ±0.5 mmol/l (104 mg/dl), p < 0.001). In addition, TGs were reduced (–0.2 ±0.3 mmol/l (18 mg/dl), p = 0.039).”

What the sources say

• Not checked yetcites [268] Lee IT Lee WJ Tsai CM Su IJ Yen HT Sheu WH Combined extractives of red yeast rice, bitter gourd, chlorella, soy protein, and licorice improve total cholesterol, low-density lipoprotein cholesterol, and triglyceride in subjects with metabolic syndrome Nutr Res 2012 32 85 92 22348456

In the paper

“The results showed a reduction of LDL-C and TG, and an increase of HDL-C after the first 3 months of treatment; the lipid profile worsened after a 2-month washout period and improved again when the nutraceutical combination was reintroduced for a further 3 months [263].”

What the sources say

• Not checked yetcites [263] Derosa G Bonaventura A Bianchi L Berberis aristata/Silybum marianum fixed combination on lipid profile and insulin secretion in dyslipidemic patients Expert Opin Biol Ther 2013 13 1495 506 23971720

In the paper

“In particular, 75% of subjects reached an LDL-C target of less than 160 mg/dl and 25% of less than 130 mg/dl.”

What the sources say

• Not checked yetcites [267] Cicero AF Derosa G Pisciotta L Barbagallo C SISA-PUFACOL Study Group Testing the short-term efficacy of a lipid-lowering nutraceutical in the setting of clinical practice: a multicenter study J Med Food 2015 18 1270 3 26274827 PMC4638196

In the paper

“The combination of γ-oryzanol (40 mg) with ω-3 polyunsaturated fatty acids (1100 mg) was demonstrated to improve lipid profile (LDL-C –0.93 ±0.97 mmol/l (36 mg/dl), p < 0.0001, TG –0.60 ±0.63 mmol/l (23.2 mg/dl), all p < 0.001), as well as inflammatory and oxidative status in dyslipidemic volunteers [272].”

What the sources say

• Not checked yetcites [272] Accinni R Rosina M Bamonti F Effects of combined dietary supplementation on oxidative and inflammatory status in dyslipidemic subjects Nutr Metab Cardiovasc Dis 2006 16 121 7 16487912

In the paper

“The improvement in lipid profile included a reduction of LDL-C from 3.5 ±0.7 mmol/l (135 mg/dl) to 3.1 ±0.8 mmol/l (120 mg/dl) after the intake of the nutraceutical product (p < 0.01). Moreover, this combination led to a reduction of plasma apoB concentrations (p < 0.01) [269].”

What the sources say

• Not checked yetcites [269] Shrestha S Volek JS Udani J A combination therapy including psyllium and plant sterols lowers LDL cholesterol by modifying lipoprotein metabolism in hypercholesterolemic individuals J Nutr 2006 136 2492 7 16988115

In the paper

“Based on the available data, no serious safety concerns have been raised, but further studies with a long follow-up are still necessary to confirm this.”

In the paper

“After 8 weeks of treatment, there was observed a significant improvement in LDL-C (–24%), TG (–19%), non-HDL-C (–22%), fasting insulin (–5%) and HOMA index (–10%) [262].”

What the sources say

• Not checked yetcites [262] Cicero AF Rosticci M Parini A Short-term effects of a combined nutraceutical of insulin-sensitivity, lipid level and indexes of liver steatosis: a double-blind, randomized, cross-over clinical trial Nutr J 2015 14 30 25886384 PMC4410738

In the paper

“No safety concerns. Very limited data; further studies are necessary.”

In the paper

“The association of pea protein + oat fiber also showed 4% glucose reduction, 57% insulin reduction and 25% decrease of the HOMA index [273].”

What the sources say

• Not checked yetcites [273] Sirtori CR Triolo M Bosisio R Hypocholesterolaemic effects of lupin protein and pea protein/fibre combinations in moderately hypercholesterolaemic individuals Br J Nutr 2012 107 1176 83 22032303

In the paper

“Doubling the daily dose seemed not to add additional benefits, while there were no safety concerns also with the higher dosage [255].”

What the sources say

• Not checked yetcites [255] Barrat E Zaïr Y Sirvent P Effect on LDL-cholesterol of a large dose of a dietary supplement with plant extracts in subjects with untreated moderate hypercholesterolaemia: a randomised, double-blind, placebo-controlled study Eur J Nutr 2013 52 1843 52 23266743

In the paper

“No safety concerns. Very limited data; further studies are necessary.”

In the paper

“The association of plant sterols/stanols with certain lipid-lowering ingredients was demonstrated to strengthen cholesterol-lowering efficacy and add TG-lowering effects [250].”

What the sources say

• Not checked yetcites [250] Kamal-Eldin A Moazzami A Plant sterols and stanols as cholesterol-lowering ingredients in functional foods Recent Pat Food Nutr Agric 2009 1 1 14 20653521

In the paper

“After the active treatment, there was observed a significant improvement in LDL-C (–18.2%), non-HDL-C (–15%), glutamic oxaloacetic transaminase (–10%), glutamate-pyruvate transaminase (–30.9%), and hs-CRP (–18.2%) vs. placebo.”

What the sources say

• Not checked yetcites [256] Cicero AF Colletti A Fogacci F Bove M Rosticci M Borghi C Effects of a combined nutraceutical on lipid pattern, glucose metabolism and inflammatory parameters in moderately hypercholesterolemic subjects: a double-blind, cross-over, randomized clinical trial High Blood Press Cardiovasc Prev 2016 24 13 8 27339779 PMC5315731

In the paper

“After 6 months of active treatment, the results showed a more favourable percentage change in LDL-C (–26.3%; p < 0.05), endothelial reactivity (PV displacement: +6.0%; p < 0.05) and arterial stiffness (PWV: –4.7%; p < 0.05) [260].”

What the sources say

• Not checked yetcites [260] Cicero AF Morbini M Rosticci M D’Addato S Grandi E Borghi C Middle-term dietary supplementation with red yeast rice plus coenzyme Q10 improves lipid pattern, endothelial reactivity and arterial stiffness in moderately hypercholesterolemic subjects Ann Nutr Metab 2016 68 213 9 27055107

In the paper

“No safety concerns. Very limited data; further studies are necessary.”

In the paper

“After 4 weeks of the active treatment patients experienced an improvement of cholesterol levels (LDL-C –22.36%; non-HDL-C –22.83%), hs-CRP –2.33% and endothelial function (PV displacement after monacolin treatment, 18.59%) [261].”

What the sources say

• Not checked yetcites [261] Cicero AF Morbini M Parini A Effect of red yeast rice combined with antioxidants on lipid pattern, hs-CRP level, and endothelial function in moderately hypercholesterolemic subjects Ther Clin Risk Manag 2016 12 281 6 26966368 PMC4770063

In the paper

“The combination of phytosterols and ω-3 PUFAs reduced LDL-C by 12.5% (p = 0.002) and TG by 25.9% (p = 0.005); moreover, it increased HDL-C (8.6%, p = 0.04) [270].”

What the sources say

• Not checked yetcites [270] Micallef MA Garg ML The lipid-lowering effects of phytosterols and (n-3) polyunsaturated fatty acids are synergistic and complementary in hyperlipidemic men and women J Nutr 2008 138 1085 90 18492838

In the paper

“Clinical trials have reported that many nutraceuticals have an additive effect to lipid-lowering drugs, allowing the statin doses to be reduced without diminishing the results in terms of TC and LDL-C reduction and significantly limiting adverse effects [281].”

What the sources say

• Not checked yetcites [281] Cicero AF Colletti A Banach M Statins and nutraceuticals/functional food: could they be combined? Combination Therapy In Dyslipidemia 2016 127 42

In the paper

“No safety concerns. Very limited data; further studies are necessary.”

In the paper

“No safety concerns; limited data – further studies are necessary.”

In the paper

“All reported side effects lasted a few days and did not lead to interruption of treatment [291].”

What the sources say

• Not checked yetcites [291] Di Pierro F Bellone I Rapacioli G Putignano P Clinical role of a fixed combination of standardized Berberis aristata and Silybum marianum extracts in diabetic and hypercholesterolemic patients intolerant to statins Diabetes Metab Syndr Obes 2015 8 89 96 25678808 PMC4322873

In the paper

“In addition, TGs were reduced by 36% and HDL-C increased by 37%, an effect that was significantly higher when compared to the use of rosuvastatin alone.”

What the sources say

• Not checked yetcites [120] Gliozzi M Walker R Muscoli S Bergamot polyphenolic fraction enhances rosuvastatin-induced effect on LDL-cholesterol, LOX-1 expression and protein kinase B phosphorylation in patients with hyperlipidemia Int J Cardiol 2013 170 140 5 24239156

In the paper

“No safety concerns; limited data – further studies are necessary.”

In the paper

“It also increased the serum lathosterol/cholesterol ratio (p < 0.01), thus showing upregulation of cholesterol synthesis, and increased the serum sitosterol ratio (p < 0.01).”

What the sources say

• Not checked yetcites [293] Gylling H Miettinen TA LDL cholesterol lowering by bile acid malabsorption during inhibited synthesis and absorption of cholesterol in hypercholesterolemic coronary subjects Nutr Metab Cardiovasc Dis 2002 12 19 23 12125225

In the paper

“The results highlighted that simvastatin reduced LDL-C by 39% (p < 0.001) and additional stanol ester margarine reduced it by a further 13% (p < 0.05).”

What the sources say

• Not checked yetcites [293] Gylling H Miettinen TA LDL cholesterol lowering by bile acid malabsorption during inhibited synthesis and absorption of cholesterol in hypercholesterolemic coronary subjects Nutr Metab Cardiovasc Dis 2002 12 19 23 12125225

In the paper

“No safety concerns; limited data – further studies are necessary.”

In the paper

“No safety concerns; limited data – further studies are necessary.”

In the paper

“Ezetimibe and nutraceuticals have been both introduced, alone or in association, as alternative therapies for statin-intolerant patients and proved to be effective and well tolerated.”

In the paper

“No safety concerns; limited data – further studies are necessary.”

In the paper

“Compared with baseline, atorvastatin 40 mg showed a reduction of LDL-C (22%, p < 0.05), and increased β-sitosterol, campesterol/cholesterol, and β-sitosterol/cholesterol ratios (39%, 47%, and 32%, respectively, p < 0.05); ezetimibe 10 mg reduced campesterol and campesterol/cholesterol ratio (67% and 70%, respectively, p < 0.05), while the combined therapy decreased LDL-C (38%, p < 0.05), campester”

What the sources say

• Not checked yetcites [292] Malina DM Fonseca FA Barbosa SA Additive effects of plant sterols supplementation in addition to different lipid-lowering regimens J Clin Lipidol 2015 9 542 52 26228672

In the paper

“Among patients treated with highly effective lipid-lowering therapy, the intake of 25 g of fibers added favorable effects: a reduction of phytosterolemia, improvement in blood glucose (p = 0.047), weight loss (p = 0.04) and reduced body mass index (p = 0.002) [288].”

What the sources say

• Not checked yetcites [288] Ramos SC Fonseca FA Kasmas SH The role of soluble fiber intake in patients under highly effective lipid-lowering therapy Nutr J 2011 10 80 21810257 PMC3159132

In the paper

“It was observed that the combined therapy significantly reduced LDL-C (–53%) compared to rosuvastatin alone, an effect which was nearly the same as the one produced by 20 mg of rosuvastatin.”

What the sources say

• Not checked yetcites [120] Gliozzi M Walker R Muscoli S Bergamot polyphenolic fraction enhances rosuvastatin-induced effect on LDL-cholesterol, LOX-1 expression and protein kinase B phosphorylation in patients with hyperlipidemia Int J Cardiol 2013 170 140 5 24239156

In the paper

“The intake of berberine/silymarin with statins led to an improvement of lipid parameters (LDL-C –15% and –28%, respectively after 6 and 12 months) and also when added to ezetimibe (LDL-C –20% and –33% respectively after 6 and 12 months).”

What the sources say

• Not checked yetcites [291] Di Pierro F Bellone I Rapacioli G Putignano P Clinical role of a fixed combination of standardized Berberis aristata and Silybum marianum extracts in diabetic and hypercholesterolemic patients intolerant to statins Diabetes Metab Syndr Obes 2015 8 89 96 25678808 PMC4322873

In the paper

“The triple treatment led to 67% reduction from baseline (p < 0.001), with all LDL-C values being < 2.6 mmol/l, and increased HDL-C by 15% (p < 0.01).”

What the sources say

• Not checked yetcites [293] Gylling H Miettinen TA LDL cholesterol lowering by bile acid malabsorption during inhibited synthesis and absorption of cholesterol in hypercholesterolemic coronary subjects Nutr Metab Cardiovasc Dis 2002 12 19 23 12125225

In the paper

“Data from a long-term randomized clinical trial support the concept that combining statins with ω-3 fatty acids seems to further decrease CHD risk by 19% in primary prevention [284] and CHD mortality by 17% in secondary prevention [285].”

What the sources say

• Not checked yetcites [284] Yokoyama M Origasa H Matsuzaki M Japan EPA lipid intervention study (JELIS) investigators Lancet 2007 369 1090 8
• Not checked yetcites [285] Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto miocardico Lancet 1999 354 447 55 10465168

In the paper

“No safety concerns; limited data – further studies are necessary.”

In the paper

“After 8 weeks, the mean lowering of LDL-C (–63 mg/dl/–1.63 mmol/l; p = 0.03) in the group receiving 20 mg of simvastatin plus placebo was the same as that in the group receiving 10 mg of simvastatin plus psyllium and was greater than that obtained with 10 mg of simvastatin plus placebo (55 mg/dl/1.42 mmol/l; p = 0.03).”

What the sources say

• Not checked yetcites [287] Moreyra AE Wilson AC Koraym A Effect of combining psyllium fiber with simvastatin in lowering cholesterol Arch Intern Med 2005 165 1161 6 15911730

In the paper

“No safety concerns; limited data – further studies are necessary.”

In the paper

“This study demonstrated that the addition of plant sterols further reduced LDL-C by ~6.5% in the atorvastatin therapy group and 5.0% and 4.0% in the combined therapy group (p < 0.05 for all) [292].”

What the sources say

• Not checked yetcites [292] Malina DM Fonseca FA Barbosa SA Additive effects of plant sterols supplementation in addition to different lipid-lowering regimens J Clin Lipidol 2015 9 542 52 26228672

In the paper

“Similar results were reported for apoB and TC, while there were not observed significant changes of TG or HDL-C levels [287].”

What the sources say

• Not checked yetcites [287] Moreyra AE Wilson AC Koraym A Effect of combining psyllium fiber with simvastatin in lowering cholesterol Arch Intern Med 2005 165 1161 6 15911730

In the paper

“These therapies led to similar reductions in LDL-C and TC (p < 0.001 vs. baseline), while no change was observed in HDL-C.”

What the sources say

• Not checked yetcites [288] Ramos SC Fonseca FA Kasmas SH The role of soluble fiber intake in patients under highly effective lipid-lowering therapy Nutr J 2011 10 80 21810257 PMC3159132

In the paper

“Patients who followed 8-week treatment with simvastatin (10 mg) plus placebo obtained a significant reduction in non-HDL-C (–10.8%), TG (–6.9%), and LDL-C (–11.6%) (p ≤ 0.01), and an increase in HDL-C (+10.4%) (p = 0.02).”

What the sources say

• Not checked yetcites [295] Ahmad Alobaidi AH Effect of Nigella sativa and Allium sativum coadminstered with simvastatin in dyslipidemia patients: a prospective, randomized, double-blind trial Antiinflamm Antiallergy Agents Med Chem 2014 13 68 74 23848231

In the paper

“After 4 weeks of treatment, the mean LDL-C and TG levels in the group receiving 20 mg of lovastatin plus 10 g of psyllium fell by 30.9% and 26.2% from baseline compared with 24.8% and 32.9% in the group receiving 20 mg of lovastatin and 3.6% and 10.9% in the group receiving 10 g of psyllium, respectively [286].”

What the sources say

• Not checked yetcites [286] Agrawal AR Tandon M Sharma PL Effect of combining viscous fibre with lovastatin on serum lipids in normal human subjects Int J Clin Pract 2007 61 1812 8 17935545

In the paper

“No safety concerns; limited data – further studies are necessary.”

In the paper

“Moreover, a significant reduction of biomarkers used for detecting oxidative vascular damage was reported, suggesting antioxidant activity of bergamot in patients on statin therapy [120].”

What the sources say

• Not checked yetcites [120] Gliozzi M Walker R Muscoli S Bergamot polyphenolic fraction enhances rosuvastatin-induced effect on LDL-cholesterol, LOX-1 expression and protein kinase B phosphorylation in patients with hyperlipidemia Int J Cardiol 2013 170 140 5 24239156

In the paper

“This is particularly relevant since it is estimated that the range of people intolerant to conventional statin treatment is between 45 000 and 290 000 individuals/year [36]”

What the sources say

• Not checked yetcites [36] Bangalore S Fayyad R Hovingh GK Treating to New Targets Steering Committee and Investigators Statin and the risk of renal-related serious adverse events: analysis from the IDEAL, TNT, CARDS, ASPEN, SPARCL, and other placebo-controlled trials Am J Cardiol 2014 113 2018 20 24793673

In the paper

“Another group of patients who might benefit from such nutraceuticals consists of very old patients (especially those aged over 75) or patients with sarcopenia [40].”

What the sources say

• Not checked yetcites [40] Banach M Serban MC Discussion around statin discontinuation in older adults and patients with wasting diseases J Cachexia Sarcopenia Muscle 2016 7 396 99 27030814 PMC4782254

In the paper

“The development of new powerful (and very expensive) lipid-lowering drugs will be able to fill the gap (and in consequence reduce the residual CV risk)”

What the sources say

• Not checked yetcites [41] Banach M Aronow WS Serban MC Rysz J Voroneanu L Covic A Lipids, blood pressure and kidney update 2015 Lipids Health Dis 2015 14 167 26718096 PMC4696333

In the paper

“in the absence of an increased risk of cancer or non-CV-related death [13].”

What the sources say

• Not checked yetcites [13] Baigent C Blackwell L Emberson J Cholesterol Treatment Trialists’ (CTT) Collaboration Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials Lancet 2010 376 1670 81 21067804 PMC2988224

In the paper

“Levels of LDL-C < 100 mg/dl (~2.5 mmol/l) are associated with a low risk for CHD and are considered optimal in the absence of CVD or other risk factors [17].”

What the sources say

• Not checked yetcites [17] Law MR Wald NJ Thompson SG By how much and how quickly does reduction in serum cholesterol concentration lower risk of ischaemic heart disease? BMJ 1994 308 367 72 8043072 PMC2539460

In the paper

“Moreover, they can have a large number of positive pleiotropic effects, including improvement of endothelial dysfunction and arterial stiffness, as well as anti-inflammatory and anti-oxidative properties [33].”

What the sources say

• Not checked yetcites [33] Houston M The role of nutraceutical supplements in the treatment of dyslipidemia J Clin Hypertens 2012 14 121 32 PMC9645405 22277145

In the paper

“(complete statin intolerance is estimated at less than 5%)”

What the sources say

• Not checked yetcites [36] Bangalore S Fayyad R Hovingh GK Treating to New Targets Steering Committee and Investigators Statin and the risk of renal-related serious adverse events: analysis from the IDEAL, TNT, CARDS, ASPEN, SPARCL, and other placebo-controlled trials Am J Cardiol 2014 113 2018 20 24793673

In the paper

“Elevated total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) blood concentrations are the major modifiable risk factors for coronary heart disease (CHD), whereas high concentrations of plasma high-density lipoprotein cholesterol (HDL-C) in certain conditions are considered protective [6].”

What the sources say

• Not checked yetcites [6] Australian Institute of Health and Welfare High Blood Cholesterol. Cat. No. AUS 156 2012-2013 Canberra Australian Institute of Health and Welfare

In the paper

“PS also intensify the expression of ABCA1 transporter and inhibit the acyl-CoA:cholesterol O-acyltransferase (ACAT) enzyme, reducing the amount of cholesterol absorbed from 30% to 50%.”

What the sources say

• Not checked yetcites [44] Ras RT Hiemstra H Lin Y Vermeer MA Duchateau GS Trautwein EA Consumption of plant sterol-enriched foods and effects on plasma plant sterol concentrations: a meta-analysis of randomized controlled studies Atherosclerosis 2013 230 336 46 24075766
• Not checked yetcites [45] Ferguson JJ Stojanovski E MacDonald-Wicks L Garg ML Fat type in phytosterol products influence their cholesterol-lowering potential: a systematic review and meta-analysis of RCTs Prog Lipid Res 2016 64 16 29 27497855

In the paper

“In 2010 the European Food Safety Authority (EFSA) confirmed that oat β-glucan is able to reduce plasmatic cholesterol levels; however, at least 3 g/day of β-glucan is necessary [54].”

What the sources say

• Not checked yetcites [54] EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) Scientific opinion on the substantiation of a health claim related to oat beta-glucan and lowering blood cholesterol and reduced risk of (coronary) heart disease pursuant to Article 14 of Regulation (EC) No 1924/2006 EFSA J 2010 8 188

In the paper

“β-glucan has high viscosity, which confers lipid-lowering action [32].”

What the sources say

• Not checked yetcites [32] Sahebkar A Serban MC Gluba-Brzózka A Lipid-modifying effects of nutraceuticals: an evidence-based approach Nutrition 2016 32 1179 92 27324061

In the paper

“The reduction of cholesterol obtained by soluble fibers described in the literature is variable and dependent on the type of fiber, doses, subjects treated, study size and different diets: the effective range of the reduction of TC varies from 0 to 18% for oat-based fibers, 3–17% for psyllium, 5–16% for pectin, and 4–17% for guar gum [51].”

What the sources say

• Not checked yetcites [51] Brown L Rosner B Willett WW Sacks FM Cholesterol-lowering effects of dietary fiber: a meta-analysis Am J Clin Nutr 1999 69 30 42 9925120

In the paper

“The level of evidence and the strength of recommendation of particular lipid-lowering treatment options have been weighed and graded according to predefined scales, as outlined in Tables I and II.”

In the paper

“However, in some cases minor gastrointestinal side effects were reported (especially with micronized fibers) that might slightly reduce the adherence to this nutraceutical [64].”

What the sources say

• Not checked yetcites [64] Anderson JW Allgood LD Lawrence A Cholesterol-lowering effects of psyllium intake adjunctive to diet therapy in men and women with hypercholesterolemia: meta-analysis of 8 controlled trials Am J Clin Nutr 2000 71 472 9 10648260

In the paper

“The experts of the writing and reviewing panels completed Declaration of interest forms where real or potential sources of conflicts of interest might be perceived (at the end of the paper).”

In the paper

“The mechanisms of action of psyllium are similar to those of other fibers discussed, including increased excretion of bile acids (stimulating 7α-hydroxylase), reduced absorption of intestinal cholesterol and a reduction of hepatic cholesterol synthesis (via the short-chain fatty acid byproducts of fiber fermentation) [58].”

What the sources say

• Not checked yetcites [58] Anderson JW Dietary fibre, complex carbohydrate and coronary artery disease Can J Cardiol 1995 11 Suppl G 55G 62G 7585294

In the paper

“Unlike other fibers, glucomannan does not act by binding bile acids, but it seems to reduce the absorption of cholesterol in the jejunum and the absorption of bile acids in the ileum, yielding improvements in apolipoprotein B (ApoB) and plasma LDL-C levels.”

What the sources say

• Not checked yetcites [65] Behera SS Ray RC Konjac glucomannan, a promising polysaccharide of Amorphophallus konjac K. Koch in health care Int J Biol Macromol 2016 92 942 56 27481345

In the paper

“PS have also shown a high safety profile in the middle-term; however, data for treatment longer than 2 years are still not available [44, 50].”

What the sources say

• Not checked yetcites [44] Ras RT Hiemstra H Lin Y Vermeer MA Duchateau GS Trautwein EA Consumption of plant sterol-enriched foods and effects on plasma plant sterol concentrations: a meta-analysis of randomized controlled studies Atherosclerosis 2013 230 336 46 24075766
• Not checked yetcites [50] Gylling H Halonen J Lindholm H The effects of plant stanol ester consumption on arterial stiffness and endothelial function in adults: a randomised controlled clinical trial BMC Cardiovasc Disord 2013 13 50 23841572 PMC3717082

In the paper

“The lipid-lowering effect of PS is dose dependent and proportional up to the attainment of a plateau (reached at approximately 3 g/day of PS achieving an average effect on LDL-C of –12%)”

What the sources say

• Not checked yetcites [48] Talati R Sobieraj DM Makanji SS Phung OJ Coleman CI The comparative efficacy of plant sterols and stanols on serum lipids: a systematic review and meta-analysis J Am Diet Assoc 2010 110 719 26 20430133

In the paper

“The meta-analysis showed not only the significant reduction of LDL-C of 0.33 mmol/l (12.8 mg/dl) (–8.5%)”

What the sources say

• Not checked yetcites [44] Ras RT Hiemstra H Lin Y Vermeer MA Duchateau GS Trautwein EA Consumption of plant sterol-enriched foods and effects on plasma plant sterol concentrations: a meta-analysis of randomized controlled studies Atherosclerosis 2013 230 336 46 24075766

In the paper

“The lipid-lowering mechanisms of action of soluble fibers are different, including prolonged gastric emptying time, an increase of satiety, the inhibition of hepatic cholesterol synthesis and an increase of fecal excretion of cholesterol and bile salts [52].”

What the sources say

• Not checked yetcites [52] Doi K Effect of konjac fibre (glucomannan) on glucose and lipids Eur J Clin Nutr 1995 49 Suppl 3 S190 7 8549522

In the paper

“A meta-analysis of 6 RCTs including 416 patients with hypercholesterolemia concluded that it has a significant effect on TC (–0.3 mmol/l (11.6 mg/dl), p = 0.002), but not on LDL-C, HDL-C or TG [71].”

What the sources say

• Not checked yetcites [71] Baker WL Tercius A Anglade M White CM Coleman CI A meta-analysis evaluating the impact of chitosan on serum lipids in hypercholesterolemic patients Ann Nutr Metab 2008 55 368 74 19923803

In the paper

“It was also estimated that following RYR treatment for 4 years, the number needed to treat (NNT) to prevent one coronary event, one coronary death and one mortality due to all causes in elderly patients were respectively 18, 33 and 23. In adults, however, these numbers were 23, 82 and 51.”

What the sources say

• Not checked yetcites [93] DFG Permanent Senate Commission on Food Safety Toxicological evaluation of red mould rice: an update 2012

In the paper

“Probiotics are considered to be generally very safe, and side effects are rare.”

What the sources say

• Not checked yetcites [84] Doron S Snydman DR Risk and safety of probiotics Clin Infect Dis (Review) 2015 60 Suppl 2 S129 34 PMC4490230 25922398

In the paper

“A stronger cholesterol-lowering effect of Lactobacillus was confirmed in the meta-analysis of RCTs by Shimizu et al., where the most promising results were obtained after a treatment period of more than 4 weeks”

What the sources say

• Not checked yetcites [83] Shimizu M Hashiguchi M Shiga T Tamura HO Mochizuki M Meta-analysis: effects of probiotic supplementation on lipid profiles in normal to mildly hypercholesterolemic individuals PLoS One 2015 10 e0139795 26473340 PMC4608827

In the paper

“In a meta-analysis of 39 RCTs enrolling 2298 mild-to-moderate hypercholesterolemic subjects the consumption of garlic extracts for at least 2 months showed a reduction of LDL-C (–0.23 mmol/l (9 mg/dl), more evident in individuals with TC < 5.17 mmol/l (200 mg/dl) at baseline) [103].”

What the sources say

• Not checked yetcites [103] Ried K Toben C Fakler P Effect on garlic on serum lipids: an updated meta-analysis Nutr Rev 2013 71 282 99 23590705

In the paper

“This gender-dependent effect was also observed with other soluble fibers, and it would seem to be caused by the interaction between sex hormones and lipid metabolism; nevertheless, further corroboration is necessary [69].”

What the sources say

• Not checked yetcites [69] Martino F Martino E Morrone F Carnevali E Forcone R Niglio T Effect of dietary supplementation with glucomannan on plasma total cholesterol and low density lipoprotein cholesterol in hypercholesterolemic children Nutr Metab Cardiovasc Dis 2005 15 174 80 15955465

In the paper

“RYR supplementation showed a reduction in the risk of CHD (31.0%, p = 0.04), all-cause mortality (31.9%, p = 0.01), stroke (44.1%, p = 0.04), the need for coronary artery bypass graft (CABG) or a percutaneous coronary intervention (PCI) (48.6%, p = 0.07) and malignancies (51.4%, p = 0.03).”

What the sources say

• Not checked yetcites [93] DFG Permanent Senate Commission on Food Safety Toxicological evaluation of red mould rice: an update 2012

In the paper

“The results showed that the group treated with RYR at the end of the 6-week follow-up obtained a reduction of hs-CRP and the area under the curve (AUC) of triglyceride (TG-AUC) (p < 0.001 for each), in addition to an improvement of postprandial and pre-prandial FMD (p < 0.001). There were no significant changes in serum lipids and FMD in the placebo group [92].”

What the sources say

• Not checked yetcites [92] Zhao SP Liu L Cheng YC Xuezhikang, an extract of cholestin, protects endothelial function through antiinflammatory and lipid-lowering mechanisms in patients with coronary heart disease Circulation 2004 110 915 20 15313947

In the paper

“The intake of glucomannan may interfere with the absorption of certain drugs, in particular lipophilic drugs/nutraceuticals: for example, glucomannan could reduce the absorption of vitamin E, calcium and other minerals, whereas it does not hinder the absorption of water-soluble vitamins.”

What the sources say

• Not checked yetcites [32] Sahebkar A Serban MC Gluba-Brzózka A Lipid-modifying effects of nutraceuticals: an evidence-based approach Nutrition 2016 32 1179 92 27324061

In the paper

“Jung et al. [106] underlined that it is able to reduce apoB and increase the LDL/Apo B ratio.”

What the sources say

• Not checked yetcites [106] Jung ES Park SH Choi EK Reduction of blood lipid parameters by a 12-wk supplementation of aged black garlic: a randomized controlled trila Nutrition 2014 30 1034 9 24976429

In the paper

“TG and HDL-C did not change significantly compared to the control groups.”

What the sources say

• Not checked yetcites [81] Cho YA Kim J Effect of probiotics on blood lipid concentrations: a meta-analysis of randomized controlled trials Medicine 2015 94 e1714 26512560 PMC4985374

In the paper

“The report released by the Agency for Healthcare Research and Quality (2011) concluded that, although the existing probiotic clinical trials reveal no evidence of increased risk, there are not enough data to answer questions on the safety of probiotics in intervention studies with confidence [84].”

What the sources say

• Not checked yetcites [84] Doron S Snydman DR Risk and safety of probiotics Clin Infect Dis (Review) 2015 60 Suppl 2 S129 34 PMC4490230 25922398

In the paper

“The consumption of probiotics is considered safe and free of serious side effects [76].”

What the sources say

• Not checked yetcites [76] Guarner F Schaafsma GJ Probiotics Int J Food Microbiol 1998 39 237 8 9553803

In the paper

“The reduction of serum triglycerides is a peculiarity of glucomannan, probably due to its high viscosity and its ability to interact with the hepatic cholesterol and lipoprotein metabolism, but not of other soluble fibers, which have only a very modest action on triglyceride levels [66].”

What the sources say

• Not checked yetcites [66] Sood N Baker WL Coleman CI Effect of glucomannan on plasma lipid and glucose concentrations, body weight, and blood pressure: systematic review and meta-analysis Am J Clin Nutr 2008 88 1167 75 18842808

In the paper

“Side effects are usually minimal (mostly gastrointestinal) and the extracts are well tolerated [104].”

What the sources say

• Not checked yetcites [104] Ackermann RT Mulrow CD Ramirez G Gardner CD Morbidoni L Lawrence VA Garlic shows promise for improving some cardiovascular risk factors Arch Intern Med 2001 161 813 24 11268223

In the paper

“Data on weight reduction are controversial; in general it can be said that glucomannan is able to promote the maintenance of weight and in some cases (with at least 5.2 weeks of treatment) it can cause a small reduction of weight (according to some meta-analyses significant, according to others not), although only less than 1 kg [67].”

What the sources say

• Not checked yetcites [67] Onakpoya I Posadzki P Ernst E The efficacy of glucomannan supplementation in overweight and obesity: a systematic review and meta-analysis of randomized clinical trials J Am Coll Nutr 2014 33 70 8 24533610

In the paper

“The effects of berberine on lipids were: LDL-C: –0.65 mmol/l (95% CI: –0.75; –0.56, p = 0.00001) (25.14 mg/dl); TG: –0.39 mmol/l (95% CI: –0.59; –0.19, p = 0.0001) (34.5 mg/dl); HDL-C: 0.07 mmol/l (95% CI: 0.04; 0.10, p = 0.00001) (2.71 mg/dl).”

What the sources say

• Not checked yetcites [138] Lan J Zhao Y Dong F Meta-analysis of the effect and safety of berberine in the treatment of type 2 diabetes mellitus, hyperlipemia and hypertension J Ethnopharmacol 2015 161 69 81 25498346

In the paper

“The tolerability of policosanols is usually very good.”

In the paper

“The authors showed that following an adequate diet in comparison with placebo, pantethine 600–900 mg/day demonstrated significant (p < 0.005) and sustained reductions (from baseline to week 16) in TC (3% – 0.16 mmol/l (6 mg/dl)), LDL-C (4% – 0.10 mmol/l (4 mg/dl)) and apoB (5% – 0.0001 mmol/l (4 mg/dl)).”

What the sources say

• Not checked yetcites [113] Rumberger JA Napolitano J Azumano I Kamiya T Evans M Pantethine, a derivative of vitamin B(5) used as a nutritional supplement, favorably alters low-density lipoprotein cholesterol metabolism in low- to moderate-cardiovascular risk North American subjects: a triple-blinded placebo and diet-controlled investigation Nutr Res 2011 31 608 15 21925346

In the paper

“The cholesterol-lowering properties of lupin were also highlighted in a third RCT proving a reduction of LDL-C (–12%) comparable to the studies described previously [160].”

What the sources say

• Not checked yetcites [160] Fechner A Kiehntopf M Jahreis G The formation of short-chain fatty acids is positively associated with the blood lipid-lowering effect of lupin kernel fiber in moderately hypercholesterolemic adults J Nutr 2014 144 599 607 24572041

In the paper

“a recent one including 35 RCTs and 2670 subjects concluded that soy proteins (in particular B-conglycinin globulin) have a cholesterol-lowering effect with a mean reduction in LDL-C of 3% (–0.12 mmol/l/4.6 mg/dl), TC of 2% (–0.14 mmol/l/5.4 mg/dl) and TG of 4% (–0.06 mmol/l/5.3 mg/dl) and is able to increase HDL-C by 3% (+0.04 mmol/l/1.6 mg/dl), the effect being proportional to the baseline LDL-C”

What the sources say

• Not checked yetcites [154] Tokede OA Onabanjo TA Yansane A Gaziano JM Djoussé L Soya products and serum lipids: a meta-analysis of randomised controlled trials Br J Nutr 2015 114 831 43 26268987

In the paper

“They found that the treated group experienced a marked reduction of small dense LDL (sdLDL) and TG, and increased HDL-C levels compared to placebo.”

What the sources say

• Not checked yetcites [121] Gliozzi M Carresi C Musolino V The effect of Bergamot-derived polyphenolic fraction on LDL small dense particles and non alcoholic fatty liver disease in patients with metabolic syndrome Adv Biol Chem 2014 4 129 37

In the paper

“These effects seem to be additive to those of statins and associated with a positive impact on glucose metabolism and blood pressure as well [138].”

What the sources say

• Not checked yetcites [138] Lan J Zhao Y Dong F Meta-analysis of the effect and safety of berberine in the treatment of type 2 diabetes mellitus, hyperlipemia and hypertension J Ethnopharmacol 2015 161 69 81 25498346

In the paper

“The main limitation of the evidence on bergamot efficacy is related to the fact that the greater part of the clinical literature has been provided by a single research unit and not confirmed elsewhere.”

In the paper

“Clinical studies conducted to date with dosages between 500 and 1500 mg/day showed a good safety profile, with no side effects detected.”

In the paper

“In summary, the evidence indicates that bergamot has lipid-lowering effects, both quantitative and qualitative, especially by reducing the levels of sdLDL and TG and significantly increasing HDL-C levels.”

In the paper

“In the LPI group, the levels of HDL-C increased significantly (p < 0.036) and the LDL/HDL ratio decreased (p = 0.003), compared to the MPI group [158].”

What the sources say

• Not checked yetcites [158] Bähr M Fechner A Krämer J Kiehntopf M Jahreis G Lupin protein positively affects plasma LDL cholesterol and LDL:HDL cholesterol ratio in hypercholesterolemic adults after four weeks of supplementation: a randomized, controlled crossover study Nutr J 2013 12 107 23902673 PMC3735452

In the paper

“they seem to have direct positive effects on endothelial function [155] and arterial stiffness [156].”

What the sources say

• Not checked yetcites [155] Beavers DP Beavers KM Miller M Stamey J Messina MJ Exposure to isoflavone-containing soy products and endothelial function: a Bayesian meta-analysis of randomized controlled trials Nutr Metab Cardiovasc Dis 2012 22 182 91 20709515
• Not checked yetcites [156] Hazim S Curtis PJ Schär MY Acute benefits of the microbial-derived isoflavone metabolite equol on arterial stiffness in men prospectively recruited according to equol producer phenotype: a double-blind randomized controlled trial Am J Clin Nutr 2016 103 694 702 26843154 PMC4763500

In the paper

“The BBR group showed a marked reduction in TG (26% BBR vs. 13% control; the difference did not reach statistical significance due to large inter-individual variations) and LDL-C (24% vs. 17% BBR control: p < 0.001) compared to the control group.”

What the sources say

• Not checked yetcites [137] Meng S Wang LS Huang ZQ Berberine ameliorates inflammation in patients with acute coronary syndrome following percutaneous coronary intervention Clin Exp Pharmacol Physiol 2012 39 406 11 22220931

In the paper

“In vitro it inhibits fatty acid synthesis and HMG-CoA reductase [109, 110].”

What the sources say

• Not checked yetcites [109] Cighetti G Del Puppo M Paroni R Galli Kienle M Modulation of HMG-CoA reductase activity by pantetheine/pantethine Biochim Biophys Acta 1988 963 389 93 3196742
• Not checked yetcites [110] Cighetti G Del Puppo M Paroni R Fiorica E Galli Kienle M Pantethine inhibits cholesterol and fatty acid syntheses and stimulates carbon dioxide formation in isolated rat hepatocytes J Lipid Res 1987 28 152 61 3106549

In the paper

“In particular, the 3-hydroxy-3-methyl-glutaryl flavanone enriched fraction (HMGF: brutieridin, melitidin and HMG-neoeriocitrin) has been extracted from the bergamot peel; they act as statins by inhibiting HMG-CoA reductase and ACAT, reducing the formation of cholesterol esters and limiting the transport of cholesterol in the blood.”

What the sources say

• Not checked yetcites [118] Di Donna L De Luca G Mazzotti F Napoli A Salerno R Taverna D Sindona G Statin-like principles of bergamot fruit (Citrus bergamia): isolation of 3-hydroxymethylglutaryl flavonoid glycosides J Nat Prod 2009 72 1352 4 19572741
• Not checked yetcites [119] Miceli N Mondello MR Monforte MT Hypolipidemic effects of Citrus bergamia Risso et Poiteau juice in rats fed a hypercholesterolemic diet J Agric Food Chem 2007 55 10671 7 18038978

In the paper

“The data suggest that pantethine supplementation for 16 weeks (600 mg/day for weeks 1–8 then 900 mg/day for weeks 9–16) is safe and significantly lowers TC and LDL-C (although with relatively limited clinical relevance) over and above the effect of therapeutic lifestyle changes (TLC) or diet alone [114].”

What the sources say

• Not checked yetcites [114] Bertolini S Donati C Elicio N Lipoprotein changes induced by pantethine in hyperlipoproteinemic patients: adults and children Int J Clin Pharmacol Ther Toxicol 1986 24 630 7 3098691

In the paper

“These results were confirmed by the same author in the next randomized, controlled, double-blind three-phase crossover trial, including 72 patients with hypercholesterolemia treated for 28 days with LPI, MP (milk protein) or MPA (milk protein 1.6 g/day of arginine). In addition to reducing LDL-C levels (in MPA and LPI groups), the LPI group showed an improvement in the levels of homocysteine (comp”

What the sources say

• Not checked yetcites [159] Bähr M Fechner A Kiehntopf M Jahreis G Consuming a mixed diet enriched with lupin protein beneficially affects plasma lipids in hypercholesterolemic subjects: a randomized controlled trial Clin Nutr 2015 34 7 14 24746974

In the paper

“In summary, the use of BBR at doses ranging between 500 and 1500 mg has proved to be effective in lipid lowering and relatively safe both in primary and secondary prevention.”

In the paper

“Based on the abovementioned data, side effects are mild to moderate, mostly gastrointestinal (diarrhea, constipation, abdominal distension) and comparable to the control groups [139].”

What the sources say

• Not checked yetcites [139] Derosa G Maffioli P Cicero AF Berberine on metabolic and cardiovascular risk factors: an analysis from preclinical evidences to clinical trials Expert Opin Biol Ther 2012 12 1113 24 22780092

In the paper

“Moreover, the amount of atherogenic sdLDL significantly decreased (–35%), while large buoyant LDLs increased (+38%; both p < 0.05) compared to baseline levels.”

What the sources say

• Not checked yetcites [121] Gliozzi M Carresi C Musolino V The effect of Bergamot-derived polyphenolic fraction on LDL small dense particles and non alcoholic fatty liver disease in patients with metabolic syndrome Adv Biol Chem 2014 4 129 37

In the paper

“Usually the consumption of green tea is well tolerated; however, in some cases rash, transient elevation of blood pressure and mild gastrointestinal disorders may occur. Moreover, high doses of green tea can cause a deficiency of iron and folate due to its capacity to bind and reduce their intestinal absorption.”

What the sources say

• Not checked yetcites [143] Onakpoya I Spencer E Heneghan C Thompson M The effect of green tea on blood pressure and lipid profile: a systematic review and meta-analysis of randomized clinical trials Nutr Metab Cardiovasc Dis 2014 24 823 36 24675010

In the paper

“Compared to nutraceuticals with a statin-similar mechanism of action, BBR has a greater effect in the reduction of triglyceridemia, partly related to its positive effect on insulin-resistance [139].”

What the sources say

• Not checked yetcites [139] Derosa G Maffioli P Cicero AF Berberine on metabolic and cardiovascular risk factors: an analysis from preclinical evidences to clinical trials Expert Opin Biol Ther 2012 12 1113 24 22780092

In the paper

“Moreover, green tea is associated with an improvement in FMD [144] and pulse wave velocity (PWV) [145], despite no apparent effect on hs-CRP levels [146].”

What the sources say

• Not checked yetcites [144] Park CS Kim W Woo JS Green tea consumption improves endothelial function but not circulating endothelial progenitor cells in patients with chronic renal failure Int J Cardiol 2010 145 261 2 19962201
• Not checked yetcites [145] Lin QF Qiu CS Wang SL A cross-sectional study of the relationship between habitual tea consumption and arterial stiffness J Am Coll Nutr 2016 35 354 61 26709673
• Not checked yetcites [146] Serban C Sahebkar A Antal D Ursoniu S Banach M Effects of supplementation with green tea catechins on plasma C-reactive protein concentrations: a systematic review and meta-analysis of randomized controlled trials Nutrition 2015 31 1061 71 26233863

In the paper

“The study by Berthold et al. showed that the administration of policosanols in hypercholesterolemic patients does not statistically improve the levels of TC, TG, HDL-C and LDL-C. This trial included 143 subjects divided into five groups each treated with 10, 20, 40, 80 mg of policosanols or placebo. Nobody in any group at the end of the study (12 weeks) showed a reduction of more than 10% in LDL-C”

What the sources say

• Not checked yetcites [126] Berthold HK Unverdorben S Degenhardt R Bulitta M Gouni-Berthold I Effect of policosanol on lipid levels among patients with hypercholesterolemia or combined hyperlipidemia: a randomized controlled trial JAMA 2006 295 2262 9 16705107

In the paper

“Group D showed a reduction of LDL-C and TG (–25.0% and –27.6%, respectively; p < 0.001 for all), without any side effects [123].”

What the sources say

• Not checked yetcites [123] Mollace V Sacco I Janda E Hypolipemic and hypoglycaemic activity of bergamot polyphenols: from animal models to human studies Fitoterapia 2011 82 309 16 21056640

In the paper

“Moreover, this was accompanied by a significant reduction of serum glucose, transaminases, γ-glutamyl-transferase, and inflammatory biomarkers such as hs-CRP and tumor necrosis factor-α (TNF-α) [121].”

What the sources say

• Not checked yetcites [121] Gliozzi M Carresi C Musolino V The effect of Bergamot-derived polyphenolic fraction on LDL small dense particles and non alcoholic fatty liver disease in patients with metabolic syndrome Adv Biol Chem 2014 4 129 37

In the paper

“The tolerability of pantethine is overall high, with acceptable safety confirmed also in children [114] and patients in hemodialysis [116].”

What the sources say

• Not checked yetcites [114] Bertolini S Donati C Elicio N Lipoprotein changes induced by pantethine in hyperlipoproteinemic patients: adults and children Int J Clin Pharmacol Ther Toxicol 1986 24 630 7 3098691
• Not checked yetcites [116] Donati C Barbi G Cairo G Prati GF Degli Esposti E Pantethine improves the lipid abnormalities of chronic hemodialysis patients: results of a multicenter clinical trial Clin Nephrol 1986 25 70 4 3516477

In the paper

“The results showed dose-dependent lipid-lowering action of bergamot (groups A and B respectively LDL-C: –24.1% and –30.6%, TG: –28.2% and –37.9%, HDL-C: +22.3% and +40.1%, p < 0.001 for all) compared to baseline.”

What the sources say

• Not checked yetcites [123] Mollace V Sacco I Janda E Hypolipemic and hypoglycaemic activity of bergamot polyphenols: from animal models to human studies Fitoterapia 2011 82 309 16 21056640

In the paper

“γ-oryzanol is a mix of triterpene alcohol and sterol ferulates with lipid-lowering actions by the inhibition of HMG-CoA reductase and the reduction of intestinal cholesterol absorption [183].”

What the sources say

• Not checked yetcites [183] Mäkynen K Chitchumroonchokchai C Adisakwattana S Failla M Ariyapitipun T Effect of gamma-oryzanol on the bioaccessibility and synthesis of cholesterol Eur Rev Med Pharmacol Sci 2012 16 49 56 22338548

In the paper

“Nevertheless, a major problem is its oral bioavailability: curcumin has low solubility in water and it is a substrate of rapid metabolism. New strategies of release have been studied and tested such as phytosomal complexation with phosphatidylcholine, coadministration of piperine, using turmeric oleoresin, reducing particle size, and changing the formulation (nanoemulsion, solid lipid nanoparticle”

What the sources say

• Not checked yetcites [203] Rahimi HR Nedaeinia R Sepehri Shamloo A Nikdoust S Kazemi Oskuee R Novel delivery system for natural products: nano-curcumin formulations Avicenna J Phytomed 2016 6 383 98 27516979 PMC4967834

In the paper

“The ω-3 present in krill oil (EPA + DHA) appears to be better absorbed in the gastrointestinal tract than that found in fish oil: this is possible because of phosphatidylcholine (the main phospholipid present in krill (40%), which binds EPA and DHA), which confers greater stability to fatty acids.”

What the sources say

• Not checked yetcites [173] Cicero AF Colletti A Krill oil: evidence of a new source of polyunsaturated fatty acids with high bioavailability Clin Lipidol 2015 10 1 4

In the paper

“PUFAs might also be associated with an improvement of FMD and PWV, and, with larger dosages, with positive effects on inflammatory diseases and mood [171].”

What the sources say

• Not checked yetcites [171] Cicero AF Reggi A Parini A Borghi C Application of polyunsaturated fatty acids in internal medicine: beyond the established cardiovascular effects Arch Med Sci 2012 8 784 93 23185186 PMC3506235

In the paper

“In a study including MetS patients, treatment with 1 g/day of curcuminoids as an add-on to the standard therapy resulted in a significant reduction of LDL-C (–0.78 mmol/l (30 mg/dl), p < 0.001), TG (–0.2 mmol/l (17.7 mg/dl), p = 0.006), and Lp(a) (–0.286 μmol/l (8 mg/dl), p < 0.001) and an elevation of HDL-C (+0.18 mmol/l (7 mg/dl), p = 0.003) [196].”

What the sources say

• Not checked yetcites [196] Yang YS Su YF Yang HW Lee YH Chou JI Ueng KC Lipid-lowering effects of curcumin in patients with metabolic syndrome: a randomized, double-blind, placebo-controlled trial Phytother Res 2014 28 1770 7 25131839

In the paper

“In conclusion, omega-3 EPA and DHA represent a valid nutraceutical to reduce TG in the blood (by 18–25%) while their effects on LDL-C and HDL-C are clinically insignificant.”

In the paper

“In the most recent meta-analysis of 7 RCTs with 662 participants Ursoniu et al. found a significant reduction in plasma concentrations of LDL-C (–15.52 mg/dl (0.4 mmol/l); 95% CI: –28.43 to –2.61; p = 0.018), and TG (–14.03 mg/dl (0.16 mmol/l); 95% CI: –21.38 to –6.67; p < 0.001), and significant elevation in plasma concentrations of HDL-C (6.65 mg/dl (0.17 mmol/l); 95% CI: 2.30 to 10.99; p = 0.00”

What the sources say

• Not checked yetcites [176] Ursoniu S Sahebkar A Serban MC Lipid and Blood Pressure Meta-analysis Collaboration Group Lipid-modifying effects of krill oil in humans: systematic review and meta-analysis of randomized controlled trials Nutr Rev 2017 75 361 73 28371906

In the paper

“A relatively recent meta-analysis including data from 63 030 patients from 20 clinical trials showed that treatment with ω-3 did not have an impact on a composite CVD endpoint or total mortality but was associated with a significantly decreased rate of vascular death [181].”

What the sources say

• Not checked yetcites [181] Kotwal S Jun M Sullivan D Perkovic V Neal B Omega 3 fatty acids and cardiovascular outcomes: systematic review and meta-analysis Circ Cardiovasc Qual Outcomes 2012 5 808 18 23110790

In the paper

“Especially, it needs be noted that smaller doses than 2–4 g/day such as a low dose supplementation of a margarine with n-3 PUFAs (400 mg/day EPA + DHA) or α-linolenic acid (2 g/day) do not significantly reduce TG levels, as was confirmed in an RCT involving 4837 post-MI patients. Such supplementation also did not reduce the rate of major CVD events [180].”

What the sources say

• Not checked yetcites [180] Kromhout D Giltay EJ Geleijnse JM Alpha Omega Trial Group n-3 fatty acids and cardiovascular events after myocardial infarction N Engl J Med 2010 363 2015 26 20929341

In the paper

“However, it has to be stressed that CVD outcome studies with ω-3 have produced inconsistent results and their clinical efficacy appears to be related to non-lipid effects.”

In the paper

“A recent meta-analysis that included 7 clinical trials to assess the effect of spirulina supplementation on plasma lipid concentrations showed the lipid-lowering efficacy of spirulina, with a reduction of LDL-C by –1.07 mmol/l (41.32 mg/dl) (95% CI: –1.57; –0.57, p < 0.001), TC by 1.21 mmol/l (46.76 mg/dl) (95% CI: –1.74; –0.68, p < 0.001) and TG by –0.5 mmol/l (44.23 mg/dl) (95% CI: –0.57; –0.43,”

What the sources say

• Not checked yetcites [188] Pulido-Moran M Moreno-Fernandez J Ramirez-Tortosa C Ramirez-Tortosa M Curcumin and health Molecules 2016 21 264 26927041 PMC6273481

In the paper

“C-phycocyanin, a particular essential pigment of Spirulina, contains a phycocyanobilin, which can activate atheroprotective heme oxygenase-1 (HMOX-1), a key enzyme in the heme catabolic pathway in endothelial cells. Moreover, phycocyanin has proven antioxidant, anti-inflammatory and radical scavenging properties [187].”

What the sources say

• Not checked yetcites [187] Serban MC Sahebkar A Dragan S A systematic review and meta-analysis of the impact of Spirulina supplementation on plasma lipid concentrations Clin Nutr 2016 35 842 51 26433766

In the paper

“It was also observed that the administration of EPA or DHA individually gave comparable effects in the reduction of TG, but not other lipid parameters; in fact, DHA showed a very modest reduction of LDL-C by 5% and slightly increased HDL-C, while EPA produced no significant changes [169, 170].”

What the sources say

• Not checked yetcites [169] Trumbo P Schlicker S Yates AA Poos M Food and Nutrition Board of the Institute of Medicine, The National Academies Dietary reference intakes for energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein and amino acids J Am Diet Assoc 2002 102 1621 30 12449285
• Not checked yetcites [170] Wei MY Jacobson TA Effects of eicosapentaenoic acid versus docosahexaenoic acid on serum lipids: a systematic review and meta-analysis Curr Atheroscler Rep 2011 13 474 83 21975919

In the paper

“In addition, there was a small insignificant reduction of LDL-C of 0.06 mmol/l (2.3 mg/dl), but no differences in HDL-C [166].”

What the sources say

• Not checked yetcites [166] Eslick GD Howe PR Smith C Priest R Bensoussan A Benefits of fish oil supplementation in hyperlipidemia: a systematic review and meta-analysis Int J Cardiol 2009 136 4 16 18774613

In the paper

“Spirulina (Arthrospira platensis) is a filamentous microalga with known lipid-lowering effects, but with an unclear mechanism of action [186].”

What the sources say

• Not checked yetcites [186] Nagaoka S Shimizu K Kaneko H A novel protein C-phycocyanin plays a crucial role in the hypocholesterolemic action of Spirulina platensis concentrate in rats J Nutr 2005 135 2425 30 16177207

In the paper

“These results were confirmed in normolipidemic and borderline subjects in the meta-analysis by Leslie et al. that included 2270 individuals with optimal lipid or suboptimal TG profiles (TG < 2 mmol/l (177 mg/dl)). In studies that used more than 4 g/day of ω-3 TG were reduced by 9–26%, while a reduction of 4–51% was found with doses from 1 to 5 g/day of ω-3 [167].”

What the sources say

• Not checked yetcites [167] Leslie MA Cohen DJ Liddle DM Robinson LE Ma DW A review of the effect of omega-3 polyunsaturated fatty acids on blood triacylglycerol levels in normolipidemic and borderline hyperlipidemic individuals Lipids Health Dis 2015 14 53 26048287 PMC4488064

In the paper

“Safety: No serious side effects have been reported; most of them have been defined as mild gastrointestinal [169].”

What the sources say

• Not checked yetcites [169] Trumbo P Schlicker S Yates AA Poos M Food and Nutrition Board of the Institute of Medicine, The National Academies Dietary reference intakes for energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein and amino acids J Am Diet Assoc 2002 102 1621 30 12449285

In the paper

“In recent RCTs, supplementation with curcumin (1 g/day) was associated with a reduction of serum uric acid (p < 0.001) [199], increase of adiponectin (+76.78%, p = 0.033) levels and reduction of leptin (–26.49%, p = 0.238) [189].”

What the sources say

• Not checked yetcites [199] Panahi Y Kianpour P Mohtashami R Jafari R Simental-Mendía LE Sahebkar A Curcumin lowers serum lipids and uric acid in subjects with non-alcoholic fatty liver disease: a randomized controlled trial J Cardiovasc Pharmacol 2016 68 223 9 27124606
• Not checked yetcites [189] Panahi Y Hosseini MS Khalili N Effects of supplementation with curcumin on serum adipokine concentrations: A randomized controlled trial Nutrition 2016 32 1116 22 27297718

In the paper

“As reported in recent meta-analyses of RCTs, curcuminoids showed an increase in serum activities of superoxide dismutase (p = 0.0007) and catalase (p = 0.005) and glutathione concentrations (p = 0.01) and a reduction in serum lipid peroxides (p = 0.008) [189] and of TNF-α [190].”

What the sources say

• Not checked yetcites [189] Panahi Y Hosseini MS Khalili N Effects of supplementation with curcumin on serum adipokine concentrations: A randomized controlled trial Nutrition 2016 32 1116 22 27297718
• Not checked yetcites [190] Sahebkar A Cicero AF Simental-Mendía LE Aggarwal BB Gupta SC Curcumin downregulates human tumor necrosis factor-alpha levels: a systematic review and meta-analysis of randomized controlled trials Pharmacol Res 2016 107 234 42 27025786