Sunday, July 19, 2015

The MeDiet Project (Mediterranean Diet for Endogenous Estrogens)

The meta-analysis by Hooper, et al 2012 included 4 other fat modification trials, the last of which is this trial called MeDiet (short for Mediterranean Diet)

Studies Associated with the Trial

The Mediet Project (2002) [1]
A traditional Mediterranean diet decreases endogenous estrogens in healthy postmenopausal women (2006) [2]
Dietary enterolactone affects androgen and estrogen levels in healthy postmenopausal women (2009) [3]


The MeDiet project investigated whether a Mediterranean diet would reduce estrogen levels as: (1) previous research has found that estrogen levels are positively associated with the initiation and development of breast cancer; and (2) observational studies that found the incidence of breast cancer to be lower in southern Italy compared to northern Italy, which was related to dietary differences [1] [2]

106 postmenopausal women (aged 44-71) who met the eligibility criteria* were randomised to a Mediterranean diet group (the experimental group) or a control group for 1 year [1] [2]

“Women in the intervention group adhered to a traditional, restricted Mediterranean diet for 6 mo, whereas women in the control group continued to follow their regular diet. In particular, intervention women attended a weekly “cooking course,” followed by a social dinner, and were trained by professional chefs in the correct use of natural ingredients of a traditional Mediterranean diet. Women were then instructed to consume the same food at home using a series of recipes based on a traditional Sicilian diet. This diet included whole cereals, legumes, seeds, fish, vegetables, and other Mediterranean seasonal food containing several biologically relevant anticancer agents. Furthermore, women were asked to avoid the use of refined carbohydrates and additional animal fat, and to limit the use of salt. The dietary intervention was intended to 1) reduce the intake of both refined sugar and saturated and total fat; 2) increase the consumption of mono- and polyunsaturated fat; 3) increase the intake of fruits and vegetables (notably cruciferous plants); and 4) increase the intake of food rich in phytoestrogens.” [2]

Macronutrient intake is presented below.  In summary, both groups significantly decreased their calorie intake though to a greater extent in the experimental group (302 vs. 164).  In the experimental group this was achieved by reducing intake of animal protein, animal fat and carbohydrates, whereas the control group just reduced intake of protein and carbohydrate.  In both groups the significant reduction in carbohydrates was due to reductions in both starch and sugar [2]

* “Eligibility criteria were: (1) postmenopausal for at least 2 years; (2) no history of bilateral ovariectomy; (3) no hormone replacement therapy for the previous 1 year; (4) no history of cancer; (5) no adherence to a vegetarian or macrobiotic diet or to any other medically prescribed diet; and (6) no treatment for diabetes, thyroid disease, and chronic bowel disease” [1]


The experimental diet significantly reduced several estrogen metabolites in urine (except E2 which significantly increased) as well as total urinary estrogen (see table below) [2].  Total urinary androgens slightly increased (NS) [3].  There were also some positive correlations between androgens and enterolactone* intake [3]

* Lignin precursors of enterolactone are found in the fibre of plant foods and are metabolised to enterolactone by gut bacteria.  Enterolactone seems to work by inhibiting aromatase, which converts testosterone to estrogen, and therefore seems gets some attention, both in research regarding estrogen associated cancers such as breast and prostate cancer; and also as a potential anti-aging therapy for men

Neither of the three papers reported any data on endpoints.  What we have comes from Hooper, et al (who would have contacted the authors), which is presented below.  There weren’t many hard endpoints which is most likely due to the small size (N = 106), not strictly being a secondary prevention trial and its short duration (1 year)

Experimental (N = 51)
Control (N = 55)
Combined CVD Events
Cancer Diagnosis

Hooper, et al included MeDiet as a reduced and modified fat trial, but wasn’t much of either.  Reduced fat: the experimental group reduced total fat intake from 82.2g to 67.9g, but due to the overall reduction in calories (from both protein and carbohydrate as well), the percentage of fat only decreased by 0.95% from 37.40% to 36.45%.  Modified fat: the experimental group reduced SFA intake from 27.7g to 18.4g, but there was no reciprocal increase in either MUFA or PUFA intake.  In fact, MUFA intake decreased from 40.7g to 37.2g and PUFA intake decreased from 9.1g to 8.6g.  The ‘fat modification’ was all relative to total calories.  Therefore, it’s inappropriate to include MeDiet in either a meta-analysis on reduced fat or modified fat trials, since it is neither.  Instead, it would be more appropriate to classify it as a ‘reduced calorie, reduced SFA trial with a highly multifactorial dietary intervention plus potential behaviour modification’, making it an ‘inadequately controlled trial’

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