Scientific Opinion on the substantiation of health claims related to soy isoflavones and maintenance of bone mineral density (ID 1655) and reduction of vasomotor symptoms associated with menopause (ID 1654, 1704, 2140, 3093, 3154, 3590) (further assessment) pursuant to Article 13(1) of Regulation (EC) No 1924/2006

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Article
Panel on Dietetic Products, Nutrition and Allergies
EFSA Journal
EFSA Journal 2012;10(8):2847 [36 pp.].
doi
10.2903/j.efsa.2012.2847
Panel members at the time of adoption
Carlo Agostoni, Jean-Louis Bresson, Susan Fairweather-Tait, Albert Flynn, Ines Golly, Hannu Korhonen, Pagona Lagiou, Martinus Løvik, Rosangela Marchelli, Ambroise Martin, Bevan Moseley, Monika Neuhäuser-Berthold, Hildegard Przyrembel, Seppo Salminen, Yolanda Sanz, Sean (J.J.) Strain, Stephan Strobel, Inge Tetens, Daniel Tomé, Hendrik van Loveren and Hans Verhagen
Acknowledgements

The Panel wishes to thank the members of the Working Group on Claims for the preparatory work on this scientific opinion: Carlo Agostoni, Jean-Louis Bresson, Susan Fairweather-Tait, Albert Flynn, Ines Golly, Marina Heinonen, Hannu Korhonen, Martinus Løvik, Ambroise Martin, Hildegard Przyrembel, Seppo Salminen, Yolanda Sanz, Sean (J.J.) Strain, Inge Tetens, Hendrik van Loveren and Hans Verhagen.

Contact
Type
Opinion of the Scientific Committee/Scientific Panel
On request from
European Commission
Question Number
EFSA-Q-2012-00165
EFSA-Q-2012-00166
EFSA-Q-2012-00167
EFSA-Q-2012-00170
EFSA-Q-2012-00212
EFSA-Q-2012-00213
EFSA-Q-2012-00214
Adopted
27 June 2012
Published
7 August 2012
Last Updated
7 September 2012. This version replaces the previous one/s.
Affiliation
European Food Safety Authority (EFSA), Parma, Italy
Note
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Abstract

Following a request from the European Commission, the Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to provide a scientific opinion on health claims pursuant to Article 13 of Regulation (EC) No 1924/2006 in the framework of further assessment related to soy isoflavones and maintenance of bone mineral density and reduction of vasomotor symptoms associated with menopause. The food constituent that is the subject of the claim, soy isoflavones, is sufficiently characterised. The claimed effects, maintenance of bone mineral density and reduction of vasomotor symptoms associated with menopause, which are eligible for further assessment, are beneficial physiological effects. The proposed target populations are peri- and/or post-menopausal women. On the basis of the data presented, the Panel concludes that the evidence provided is insufficient to establish a cause and effect relationship between the consumption of soy isoflavones and maintenance of bone mineral density, and between the consumption of soy isoflavones and reduction of vasomotor symptoms associated with menopause.

Summary

This scientific output, published on 7 September 2012, replaces the earlier version published on 7 August 2012

Following a request from the European Commission, the Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to provide a scientific opinion on a list of health claims pursuant to Article 13 of Regulation (EC) No 1924/2006. The Commission has agreed with EU Member States that a certain number of Article 13 health claims would be eligible for further assessment by EFSA in order to be able to take a final decision on whether or not to include these claims in the list of permitted health claims. This opinion addresses the scientific substantiation of a health claim in relation to soy isoflavones and maintenance of bone mineral density and reduction of vasomotor symptoms during menopause. The assessment is based on the information provided by the Member States in the consolidated list of Article 13 health claims, references that EFSA has received from Member States or directly from stakeholders and the additional information provided by the competent Authorities of Germany and Austria for the further assessment of these claims.

The food constituent that is the subject of the health claims is soy isoflavones. The Panel considers that soy isoflavones are sufficiently characterised.

Maintenance of bone mineral density

The claimed effect which is eligible for further assessment relates to the maintenance of bone mineral density. The proposed target population is post-menopausal women. The Panel considers that maintenance of bone mineral density is a beneficial physiological effect.

Among the 14 studies provided which addressed the effects of soy isoflavones on bone mineral density at different bone sites in post-menopausal women, only two by the same research group reported an effect of soy isoflavones at doses of 54 mg/day at the lumbar spine and femoral neck, which was accompanied by a significant increase in markers of bone formation and a significant decrease in markers of bone resorption. Both studies were performed in early post-menopausal women with osteopenia or osteoporosis. The remaining 12 studies used doses of isoflavones up to 200 mg/day and showed no effect of soy isoflavones on bone mineral density. None of these 12 studies reported an effect of soy isoflavones on markers of bone formation or resorption. The Panel notes that five of these studies may have been underpowered to detect an effect of the intervention on bone, whereas in seven studies the number of subjects per intervention arm completing the study ranged between approximately 50 and 120.

Among the five human intervention studies which allowed conclusions to be drawn on the effects of soy isoflavones administered for 6-9 months on bone mineral density in peri/post-menopausal women, one showed a beneficial dose-response effect on bone mineral density at the lumbar spine and femoral neck at doses of 84 and 126 mg/day which may have been associated with a transient decrease in bone resorption, two studies reported a beneficial effect of 80 mg/day and 90 mg/day soy isoflavones on bone mineral density at the lumbar spine with no effect on markers of bone turnover, and two studies using doses of soy isoflavones of 91 mg/day, and 52 and 96 mg/day, one of which reported a significant decrease in markers of bone formation and resorption in the soy isoflavone group, showed no effect of soy isoflavones on bone mineral density at any site.

The Panel notes the exploratory nature and small sample size of these studies. However, the Panel considers that they provide some evidence for an effect of soy isoflavones on the attenuation of bone mineral density loss at the lumbar spine in post-menopausal women when consumed for 6-9 months, possibly mediated by a decrease in bone resorption. The Panel also notes that such changes in BMD at the lumbar spine may result from a change in the remodelling balance which may not be retained in subsequent remodelling cycles (i.e. the remodelling transient).

In weighing the evidence the Panel took into account that of 14 studies lasting ≥12 months, two studies, one of which had 30 subjects per intervention arm, showed an effect of soy isoflavones on bone mineral density at doses of 54 mg/day, whereas 12, seven of which had a sample size per study arm of at least 50 subjects, did not show an effect at doses of 40 to 200 mg/day. The Panel also took into account that these inconsistent findings cannot be explained by differences in study size, dose of soy isoflavones used, duration of the intervention, or post-menopausal status, that the changes in bone mineral density at the lumbar spine observed in some short-term studies (six to nine months) may result from a change in the remodelling balance which may not be retained in subsequent remodelling cycles (i.e. the remodelling transient), and that the evidence for a mechanism by which soy isoflavones may exert an effect on bone mass and turnover in post-menopausal women is weak.
On the basis of the data presented, the Panel concludes that the evidence provided is insufficient to establish a cause and effect relationship between the consumption of soy isoflavones and maintenance of bone mineral density in post-menopausal women.

Reduction of vasomotor symptoms associated with menopause

The claimed effect which is eligible for further assessment relates to the reduction of vasomotor symptoms associated with menopause. The proposed target population is peri- and post-menopausal women. The Panel considers that reduction of vasomotor symptoms associated with menopause is a beneficial physiological effect.
Five of the 13 RCTs which investigated the effect of soy isoflavones on frequency of hot flushes considered a total of 575 subjects for data analysis (30-119 subjects per group) with daily soy isoflavone doses of 27 to 100 mg for 3-24 months and reported a statistically significant effect of soy isoflavones on frequency of hot flushes, whereas six studies, which considered 623 subjects for data analysis (12-100 subjects per group/period) and provided 40 to 120 mg of soy isoflavones per day for six weeks to six months, did not report an effect of soy isoflavones on frequency of hot flushes, while one study did not report results of this outcome. In one study in 75 subjects, in which 70 mg/day soy isoflavones were administered for 16 weeks, the per protocol and intention-to-treat analyses led to inconsistent results with respect to an effect of soy isoflavones on hot flush frequency. The Panel notes that two of the studies might have been underpowered to detect a statistically significant effect of soy isoflavones on frequency of hot flushes.

Six of the 12 RCTs which investigated the effect of soy isoflavones on severity of hot flushes considered a total of 567 subjects for data analysis (25-119 per group) with daily soy isoflavone doses of 27 to 100 mg for 3-12 months and reported a statistically significant effect of soy isoflavones on severity of hot flushes, whereas six studies, which considered 668 subjects for data analysis (12-100 subjects per group/period) and provided 40 to 120 mg of soy isoflavones per day for six weeks to six months, did not report an effect of soy isoflavones on the severity of hot flushes.

The three RCTs in which the effect of soy isoflavones on frequency and/or severity of night sweats was examined did not find any statistically significant difference between groups.

The Panel notes that most of these RCTs were at high risk of bias due to major methodological weaknesses in the statistical analyses performed (e.g. inadequate handling or no consideration of missing data, repeated measures and/or multiple comparisons not taken into account, analysis of data with a high risk of not being normally distributed by parametric tests without verification of the assumption of the statistical test applied), and/or that data were inadequately reported.

In weighing the evidence, the Panel took into account that the evidence provided by 15 human intervention studies is inconsistent with respect to an effect of soy isoflavones on reduction of vasomotor symptoms. The Panel also took into account that most of these studies were at high risk of bias, that the inconsistent results could not be explained by dose, sample size, study duration, or baseline frequency or severity of vasomotor symptoms, and that the evidence of the proposed mechanism of action is weak.

On the basis of the data presented, the Panel concludes that the evidence provided is insufficient to establish a cause and effect relationship between the consumption of soy isoflavones and reduction of vasomotor symptoms associated with menopause.

Keywords
Soy isoflavones, bone mineral density, vasomotor symptoms, menopause, health claims
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Number of Pages
36