Research2016-10-21T21:02:11+00:00

Human Studies

Over 150 adequately controlled clinical studies (including those with Reducol®) have demonstrated that plant sterols and stanols significantly lower plasma LDL cholesterol in humans. Several clinical studies conducted by Forbes Medi-Tech with Reducol® in the US, Europe and Canada produced consistent results demonstrating a significant LDL cholesterol lowering effect. These studies utilized various food matrices such as vegetable oils, cereal bars, ready to eat cereals, margarine, milk drinks, chocolate, fruit juices, and dietary supplements. To illustrate the cholesterol lowering effects of Reducol®, results from studies involving the latter four food formats are presented.

Margarine Study with Reducol® – Jones et al, 1999

A parallel, placebo-controlled study with thirty-two men that were fed either a low fat diet of prepared foods alone, versus the same diet containing 1.5g of Reducol® per 70kg of body weight per day (6% sterols in margarine) for 30 days is shown in the figure/table below.

Table 1: Effect of Reducol® in Margarine on Total and LDL cholesterol

DAY Total Cholesterol LDL Cholesterol
% Change % Change
10 -4.6* -8.1*
20 -5.9* -9.3*
30 -8.9* -1.5*

Subjects n=16
* Percent change from placebo control is statistically significant.
Note 1: In this study, Reducol® is referred to under a former working name “Phytrol™”.
Note 2: In Tables 1-3, n= refers to the number of completed subjects in each trial group or arm.

The findings indicate an 8.9% reduction in total cholesterol compared to the control group, and more importantly, a 15.5% LDL-cholesterol reduction. HDL and triglyceride levels were not affected (data not shown). The overall reduction in LDL cholesterol from baseline was 24% and included a 9% decline caused by the low fat content of the diet during the trial. This effect is consistent with the NCEP guidelines estimate of 8-10% reduction in LDL caused by reducing saturated fat in the diet. (LINK to Resources section).

Milk-Drink Study with Reducol® (Pritchard and Beer, 2000)

The observations made in the margarine study were further confirmed in a double-blinded placebo controlled, parallel group, clinical study. The study consisted of 3 phases, screening, diet counseling for 2 weeks and the active treatment phase. In the active treatment phase, subjects (n=120), were given a milk drink containing Reducol® at dosages of 0, 0.9, 1.8, 3.6 g/d for four weeks.

Compared to placebo, total cholesterol decreased by as much as 9.1% and LDL-cholesterol decreased 13.2%, with no significant changes to HDL-cholesterol levels.

Table 2: Effect of Reducol® in Milk Drink (Pritchard and Beer, 2000)

Dose Total Cholesterol LDL Cholesterol
% Change % Change
0.9 g/day -4.3 -7.4*
1.8 g/day -5.5* -8.6*
3.6 g/day -9.1* -13.2*

% Change is statistically significant

Chocolate study with Reducol®
(De Graaf et al, 2002)

Reducol® – enriched chocolate (6% sterols in chocolate) was the focus of a randomized, double blind, placebo controlled trial conducted in the Netherlands. Over a four-week period, 62 participants consumed 3 servings per day of either Reducol®-enriched chocolate (1.8g of sterols/day) or a placebo chocolate with meals. The trial consisted of 3 phases: Screening (1 week), diet counseling (3 weeks), and active treatment (4 weeks).

Table 3: Effect of Reducol® in Chocolate on Total and LDL Cholesterol

Week Total Cholesterol LDL Cholesterol
% Change % Change
3 -4.96* -7.69*
4 -6.15* -10.37

Subjects n=31
* Statistically significant difference compared to placebo group.

In this study, total LDL-Cholesterol levels were significantly reduced (Table 2) without affecting HDL-Cholesterol and triglyceride levels (not shown).

Juice Study With Reducol®
(Emata et al 2011)

This double blinded, placebo controlled trial compared Reducol® added to either 100% pineapple or 100% orange juice (Del Monte Pacific, Heart Smart). Eighty-nine subjects were randomly assigned to receive either pineapple juice with Reducol®, or orange juice with Reducol® or a placebo pineapple or orange juice for eight weeks. The 240 mL juice cans each contained 1 g of Reducol® in the active groups. The subjects were instructed to drink one can of juice in the morning and another in the evening.

Table 4: Effect Of Reducol® In Pineapple And Orange Juices

Week % change in LDL cholesterol from baseline % change in LDL cholesterol from baseline
Pineapple Juice Orange Juice
4 -8.53* -5.74
6 -7.06* -8.46*
8 -9.41* -8.46
12 (post-trial) -5.00 -7.55
Subjects n=30 n=29

*Statistically significant difference

The effect of Reducol® pineapple juice on LDL cholesterol was statistically significant at all intervals from 4-8 weeks. The effect had reversed by Week 12 in the four weeks post-treatment. For the orange juice, although the average LDL cholesterol was reduced at 4-8 weeks, the difference was statistically significant only at Week 6.

Tablets & Softgels

Maki KC, et al. International Journal of Food Sciences and Nutrition 2012; Nutrition 2013

In a randomized, placebo-controlled, crossover trial, Reducol® tablets providing 1.8 g/day free (non-esterified) plant sterols/stanols or placebo were given to 32 participants for 6 weeks as a part of the National Cholesterol Education Program (NCEP) Therapeutic Lifestyle Changes (TLC) diet.

Table 5. Effect of Reducol® Tablets on LDL and Total Cholesterol

% Change with Placebo % Change with Reducol®
LDL 0.6 -4.3*
Total Cholesterol -0.5 -3.3*

*Statistically significant difference compared to placebo

In a randomized, placebo-controlled, crossover trial, Reducol® softgels providing esterified plant sterols/stanols 2.9 g/day (equivalent to non-esterified plant sterol/stanols 1.8 g/day) or placebo were given to 28 participants for 6 weeks as a part of the NCEP TLC diet. (Participants started the NCEP TLC diet 5 weeks prior to starting supplementation with Reducol®.)

Table 6. Effect of Reducol® Softgels on LDL and Total Cholesterol and Triglycerides

% Change with Placebo % Change with Reducol®
LDL 5.1 -4.1*
Total Cholesterol 4.0 -3.3*
Triglycerides 4.7 -4.4*

*Statistically significant difference compared to placebo

Safety

Safety Studies (Animal Models)

The available animal studies on Reducol® and other tall oil plant sterols and stanols indicate that the plant sterols and stanols are poorly absorbed from the gastrointestinal tract and are excreted via the feces (LINK to Resources section on Reducol® and human blood sterol levels). Studies carried out in accordance with international toxicology testing requirements with Reducol® and other plant sterol and stanol ingredients demonstrate that they are not genotoxic and demonstrate no reproductive or developmental toxicity. No significant side effects were noted following administration of Reducol® powder up to 5% in the diet for 13 weeks in rats studies. There was also no evidence of oestrogenic activity from the available studies on Reducol® and other phytosterol ingredients.

Human Studies

Reducol® and other phytosterol ingredients are well tolerated in human studies. The only significant side effect reported has been a reduction in blood levels of carotenes. This effect has been reported mostly in studies of sterol and stanol esters, with almost no reports when using free phytosterol ingredients. The reductions are within the normal seasonal range of variation in blood levels of beta-carotene (Katan et al 2002). The decline in carotene levels can be prevented by a diet with adequate amounts of fruits and vegetables. Regulatory authorities in the European Union require the label on foods with plant sterols and stanols to indicate that the food should be used as a part of a diet that includes regular consumption of fruit and vegetables.

Generally Recognized As Safe (GRAS) and Other Regulatory Approvals

Reducol® is GRAS (Generally Recognized as Safe) by the USA Food and Drug Administration (GRAS Notice No. GRN00039 in FDA listing). GRAS means that the safety of the food ingredient was evaluated by a panel of experts qualified by experience and training and determined to be safe under the specified conditions of use in the GRAS notification. Reducol® has been approved for use in Novel Foods in European Union, Australia-New Zealand and in Canada. Reducol® has also been approved for use in Del Monte pineapple and orange juice in the Philippines.

Safe Dose

Reducol® requires a 1.8 grams daily dosage per day for efficacy (LINK to Resources section for dose response data) – well within daily safety limits established or recommended by regulatory agencies in Europe and the United States.

References

De Graaf J, De Sauvage Nolting PR, Van Dam M, Belsey EM, Kastelein JJ, Haydn Pritchard P, Stalenhoef AF. Consumption of tall oil-derived phytosterols in a chocolate matrix significantly decreases plasma total and low-density lipoprotein-cholesterol levels. Br J Nutr. 2002 Nov;88(5):479-88.
www.ncbi.nlm.nih.gov/pubmed/12425728

*Emata DV, Gimenez LM, Tamayo NL, Gertrude C. Efficacy of plant phytosterol mixture contained in a commercial juice blend in reducing cholesterol levels amoung Filipinos 25 to 60 years of age: A randomzied, placebo-controlled, double blind trial. Phillippine J. Int. Med. 2011 Dec 49(4):223-233.
http://www.pcp.org.ph/images/stories/pjim_49/issue4_oct-dec2011/7_Effica…

*Jones PJ, Ntanios FY, Raeini-Sarjaz M, Vanstone CA. Cholesterol-lowering efficacy of a sitostanol-containing phytosterol mixture with a prudent diet in hyperlipidemic men. Am J Clin Nutr. 1999 Jun;69(6):1144-50. 10357732.
www.ncbi.nlm.nih.gov/pubmed/10357732

Katan MB, Grundy SM, Jones P, Law M, Miettinen T, Paoletti R; Stresa Workshop Participants. Efficacy and safety of plant stanols and sterols in the management of blood cholesterol levels. Mayo Clin Proc. 2003 Aug;78(8):965-78. Review.
www.ncbi.nlm.nih.gov/pubmed/12911045

*Maki KC, Lawless AL, Reeves MS, Dicklin MR, Jenks BH, Shneyvas E, Brooks JR. Lipid-altering effects of a dietary supplement tablet containing free plant sterols and stanols in men and women with primary hypercholesterolaemia: a randomized, placebo-controlled crossover trial. Int J Food Sci Nutr. 2012 Jun;63(4):476-82.
www.ncbi.nlm.nih.gov/pubmed/22087585

Maki KC, Lawless AL, Reeves MS, Kelley KM, Dicklin MR, Jenks BH, Shneyvas E, Brooks JR. Lipid effects of a dietary supplement softgel capsule containing plant sterols/stanols in primary hypercholesterolemia. Nutrition. 2012 Jul 14. [Epub ahead of print] www.ncbi.nlm.nih.gov/pubmed/22796122

Pritchard H and Beer M. The effect of increasing doses of tall oil derived phytosterols (PhytrolTM) on the plasma lipid levels of hypercholesterolemic patients. Protocol CLF 9904. Study report for Novartis Consumer Health and Forbes Medi-Tech Inc, November 14, 2000, pages 1-109.

*Publication is available free of charge