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Labelling salt in food: if yes, how?
Comment
Labelling salt in food: if yes, how? Common or table salt has been fought over, taxed (and therefore smuggled), and used in remuneration and as a political weapon, so important to daily life was this mineral. These days sodium chloride arouses passions of a different sort; it is widely seen as a threat to public health. With refrigeration and other means of food preservation, daily salt intake is now 9–11 g. But that is far too much, say various world and national authorities, who look to 5 or 6 g as a reasonable target. For example, the British Food Standards Agency has the goal of a one-third reduction, to 6·0 g by 2010.1 The UK’s Consensus Action on Salt and Health draws attention to dose-response calculations backing 3 g as something to aim for in future.2 That could, it is claimed, achieve a one-third drop in fatal strokes and a one-quarter reduction in mortality from ischaemic heart disease, which in the UK would translate to over 50 000 deaths prevented every year. If 3 g seems unrealistic, it is not that far below the 1·5 g sodium (3·75 g salt) suggested by the US National Heart, Lung, and Blood Institute3 4 years ago, on the basis of the then unpublished DASH [Dietary Approaches to Stop Hypertension]-Sodium results. The argument over the dangers of salt seems far from over, as responses to a cautious meta-analysis4 in the British Medical Journal in 2002 demonstrate. The multiplicity of Cochrane Library publications and updates on the salt/ hypertension debate 5–8 also shows what a controversial subject this remains. For one thing, rigorous randomised studies targeting large hypertensive or normotensive groups with serious reduction in salt intake over a long time are not easy to do. With the recent confident pronouncements they might even be impossible now. Another difficulty might be that the hoped-for effect on cardiovascular disease is an extrapolation from blood-pressure data. Fatal heart attacks and strokes have not been endpoints, or the numbers of such deaths have been too small to be revealing. Also controversial is the fact that the target is not just those with hypertension. The question, an old one in public health, is should population shifts in blood pressure be sought for the greater good even though not everyone will benefit? Another unresolved issue is the long-term effect of salt reduction; is there physiological adaptation over time, lessening blood-pressure differences in adults? This possibility makes confirmation of a study9 showing a programming effect, whereby salt restriction in infancy produces long-term blood-pressure lowering, all the more important. At least reducing salt intake to 6 g daily is unlikely to do harm. The Institute of Food Science and Technology has listed various recommendations from the 1990s on reference nutrient intakes and other forms of minimum daily requirement for sodium. These tend to be below the levels now being urged.10 The 2004 tables from the US Institute of Medicine include, for adults, an “adequate intake” equating www.thelancet.com Vol 364 December 11, 2004
to 3·75 g salt daily and an “upper limit” of 5·75 g.11 On Dec 8, 2004, the Institute of Medicine hosted in Washington, DC, a one-day symposium, looking at the triggers for a reexamination of a dietary reference intake. For sodium, perhaps a review is timely because the upper limit urged by some authorities and the adequate intake recommended by others are getting rather close. Also, at least for bread, the taste argument might not come into play until the reduction is more extreme than 25%.12 More such studies of how much salt can be removed before anyone notices and reaches for the compensatory salt grinder are needed. It is not unreasonable for public-health campaigns to continue, even though the debate is still alive. Those campaigns focus on three things: persuading retailers to stock less salty foods and manufacturers to lower the salt content of prepared foods; persuading the public to add less salt; and clear labelling of the salt content in items purchased. Since only 15–25% of intake is from a kitchen salt jar or added to the plate, most attention is being paid to what is on the shelves of retail outlets and on how those products are labelled. Salt producers in the USA and the UK might have kept the controversy on the boil13,14 but on the retail side there have been changes over several years. In the UK, some disappointment has been expressed at the reductions manufacturers are prepared to concede as a contribution to the government’s current target15 but there has been a downward trend. For example, bread contributes about one-sixth of daily salt intake. The British baking industry promises a 5% cut by the end of this year to add to the 12·5% and 10% reductions over the past two decades.16 If customers demand less salt, shops will want to stock such products and manufacturers will respond in turn, which brings us to labelling, which is not as easy as it sounds. One cereals manufacturer has a range of products, including individual portion packs for children. Six different packs in this range examined this month weighed 17–30 g and their sodium contents were 0·15–0·95 g per 100 g. So, if a child eats two different packs for breakfast the sums are not easy, and for a range of foodstuffs over a day they are tedious to the point of impossibility. So, is labelling a waste of time? No. Provided labels are not overloaded with information or confusing, the general rule that an informed consumer is better than an uninformed one holds. However, patients with heart problems need a lot of educational help with salt.17 Those perceiving themselves as healthy will probably need even more. Fortunately, there are different types of labelling to achieve the same end. Assuming that all sodium in the diet comes from table salt is a reasonable approximation and consumers will be more comfortable with figures for salt rather than sodium content. To think of servings or portions, rather than relying on arithmetic and grams per 100 g, sounds more like the real world, although servings 2079
Comment
Science Photo Library
Rights were not granted to include this image in electronic media. Please refer to the printed journal.
vary. Soups (along with bread and cereals, they contribute significantly to salt in our diets) can contain a lot of salt; a single bowl might carry 40% of the daily limit now recommended. However, labelling can be two-edged. One label on organic beans informs consumers that half a can will supply one of the UK government’s recommended five portions daily of fruit and vegetables. Containing “no artificial colours, preservatives, flavours or GM ingredients”, it sounds perfect. Hardly; one serving, the label also reveals, contains 2·5 g salt. Another method is Pick the Tick, a movement not restricted to Australasia but beginning there. Product endorsement needs careful handling but the Pick-the-Tick scheme appears to be well thought-out. It is not limited to salt. Basically, manufacturers pay for the right to display the logo if they meet content standards laid down by national heart foundations and monitored by independent laboratories. Customers look for the logo on a product and no longer need to squint at small type or reach for calculators. The scheme is having an effect18 but far more market penetration is required. In New Zealand, 33 tonnes of salt was removed from food items in a single year. Spread over 4 million New Zealanders the daily reduction would have had an imperceptible impact on blood pressure.19 Too many other factors involved in hypertension and cardiovascular disease (smoking, increased cholesterol, obesity, lack of exercise) are being tackled at the same time for it ever to be provable that a reduction in salt use as public policy has by itself saved lives. DASH-Sodium was an attempt to separate salt from other lifestyle changes in the senior trial. Demanding more DASH-Sodium data, a 2003 editorial by David McCarron argued that “If the quality of the diet is adequate, salt intake has little relevance to BP control for the vast majority of individuals”.20 Even in 2004 a review can still refer to salt reduction in the general population as contentious and to a “highly polarized divide” between those who support dietary salt reduction and those who oppose it.21 Given the arguments that earlier studies and systematic reviews have generated, the long2080
awaited13,20 DASH-Sodium details22 might not win over every doubter. Food labelling should include amount of salt (not sodium) per serving and per 100 g and at least a mention of the consensus maximum23 of, say, 6 g daily for adults, with suitable adjustment for products aimed at children. A simple mark of approval such as Pick the Tick, the US food guide pyramid, or the UK’s traffic light labels (a warning red for salt at 2·5 g per 100 g or more, an encouraging green for 0·25 g or less) would be a bonus, although care is needed lest the signals be internally confusing. The UK government wants to make healthy choices easier and rightly stresses the need for European agreement on simplified nutrition labelling, which would be mandatory for packaged foods.24 Public-health authorities seem impatient about salt but research on labels and on consumer preferences needs to be rigorous and not immune from the criticism that clinical and epidemiological studies of salt have faced and, arguably, survived.
David Sharp c/o The Lancet, London NW1 7BY, UK I declare I have no conflict of interest. 1
2 3
4
5 6
7 8
9
10 11
12 13
14
15
Food Standards Agency. Agency launches salt campaign. Sept 13, 2004. http://www.food.gov.uk/newsarchive/2004/sep/saltcampaignews (accessed Nov 2, 2004). He FJ, McGregor GA. How far should salt intake be reduced? Hypertension 2003: 42: 1093–99. National Institutes of Health. News release: NHLBI study shows large blood pressure benefit from reduced dietary sodium. http://www.nhlbi.nih.gov/ new/press/May17-00.htm (accessed Dec 7, 2004). Hooper L, Bartlett C, Davey Smith G, Ebrahim S. Systematic review of long term effects of advice to reduce dietary salt in adults. BMJ 2002; 325: 628. [See responses at: http://bmj.bmjjournals.com/cgi/eletters/325/7365/628 (accessed Dec 6, 2004)]. He FJ, McGregor GA. Effect of longer-term modest salt reduction on blood pressure. Cochrane Database Syst Rev 2004; 3: CD004937. Hooper L, Bartlett C, Davey Smith G, Ebrahim S. Advice to reduce dietary salt for prevention of cardiovascular disease. Cochrane Database Syst Rev 2004; 1: CD003656. Beard TC, Stowasser M. Cochrane and the salt debate. Lancet 2003; 362: 403. Jurgens G, Graudal NA. Effects of low sodium diet versus high sodium diet on blood pressure, renin, aldosterone, catecholamines, cholesterols, and triglyceride. Cochrane Database Syst Rev 2004; 1: CD004022. Geleijnse JM, Hofman A, Witteman JC, Hazebroek AA, Valkenburg HA, Grobbee DE. Long-term effects of neonatal sodium restriction on blood pressure. Hypertension 1997; 29: 913–17. Institute of Food Science and Technology. Current hot topics: salt. July 8, 2003: http//www.ifst.org/hottop17.htm (accessed Oct 26, 2004). Institute of Medicine. Dietary reference intakes (DRIs): recommended intakes for individuals, elements. Washington, DC: National Academy of Sciences, 2004. Girgis S, Neal B, Prescott J, et al. A one-quarter reduction in the salt content of bread can be made without detection. Eur J Clin Nutr 2003; 57: 616–20. Hanneman RL. Letter to Kathryn McMurry, HHS Office of Disease Prevention and Health Promotion. April 6, 2004. http://www.saltinstitute .org/pubstat/dgac-4-6-04.html (accessed Dec 2, 2004). Salt Manufacturers’ Association. Response of the Salt Manufacturers’ Association to the Salt Review of the Scientific Advisory Committee on Nutrition. Dec 23, 2002. http://www.saltsense.co.uk/releases/rel001.htm (accessed Dec 2, 2004). Food Standards Agency. Update on industry salt reduction activity— September, 2004. London: Food Standards Agency, 2004.
www.thelancet.com Vol 364 December 11, 2004
Comment
16 17
18
19
Federation of Bakers. The baking industry: salt. http://www.bakers federation.org.uk/salt.aspx (accessed Dec 2, 2004). Neily JB, Toto KH, Gardner EB, et al. Potential contributing factors to noncompliance with dietary sodium restriction in patients with heart failure. Am Heart J 2002; 143: 29–33. Williams P, McMahon A, Boustead R. A case study of sodium reduction in breakfast cereals and the impact of the Pick the Tick food information programme in Australia. Health Promot Int 2003; 18: 51–56. Young L, Swinburn B. Impact of the Pick the Tick food information programme on the salt content of food in New Zealand. Health Promot Int 2002; 17: 13–19.
20 21 22
23
24
McCarron DA. DASH-sodium trial: where are the data? Am J Hypertension 2003; 16: 92–94. O’Shaughnessy KM, Karet FE. Salt handling and hypertension. J Clin Invest 2004; 113: 1075-81. Bray GA, Vollmer WM, Sacks FM, et al. A further subgroup analysis of the DASH diet and dietary sodium levels on blood pressure: results of the DASH-Sodium Trial. Am J Cardiol 2004; 94: 222–27. Consensus Actino on Salt and Health. Salt and sodium labelling of food. http://www.hyp.ac.uk/cash/information/salt_labelling.htm (accessed Dec 2, 2004). HM Government/Department of Health. Choosing health: making healthy choices easier (Cm 6374). London: Stationery Office, 2004.
Phyto-oestrogens and the endometrium
www.thelancet.com Vol 364 December 11, 2004
Rights were not granted to include this image in electronic media. Please refer to the printed journal. Science Photo Library
Vittorio Unfer and colleagues1 recently reported a 5-year randomised double-blind study on the endometrial effects of the use of soy phyto-oestrogen in postmenopausal women. Of 154 patients receiving 150 mg isoflavones a day for 5 years, six (4%) developed endometrial hyperplasia (five simple, one complex; no endometrial hyperplasia with atypia), compared with none of 165 patients on placebo. The same group2 also reported a randomised trial of highdose phyto-oestrogens added to clomiphene citrate, to reverse the antioestrogenic effects of clomiphene on the endometrium during intrauterine insemination. The endometrium was thicker, miscarriage rates lower, and ongoing pregnancy rate higher in patients on phyto-oestrogen plus clomiphene than in those on clomiphene alone. These findings are neither surprising nor alarming, confirming what we know about phyto-oestrogens acting as a selective oestrogen-receptor modulator (SERM).3 Soy phyto-oestrogens (isoflavones genistein, daidzin, and glycitin) induce endometrial stromal-cell proliferation in vitro.4 The proliferative effect occurred at high concentrations and was 8–15% lower than that induced by oestradiol. In the presence of oestradiol, however, the isoflavones antagonised the proliferative effect of oestradiol by 10–20%, which indicates that isoflavones are weak oestrogens and their antioestrogenic effects are only seen in high concentrations when combined with physiological concentrations of oestradiol. Animal models also show that high doses of isoflavones, particularly genistein, stimulate uterine growth and expression of several genes regulated by uterine oestrogen, and isoflavones have weak oestrogenic activity in mammary gland and hypothalamic/pituitary cells. Any clinical application of these findings might result in different outcomes, possibly due to various doses and preparations used for isoflavones and individual differences in metabolism. A 4-week study of soy-supplemented diet in postmenopausal women did not have oestrogenic effects in liver and pituitary-gland function.5 In a small randomised trial, 25 mg soy-protein isolate daily with 120 mg isoflavones added to oestradiol for 6 months did not protect endometrium from oestradiol-induced hyperplasia.6
The natural history of endometrial hyperplasia is not fully understood and some simple and complex hyperplasias will regress without treatment.7 However, the time over which regression occurs is unknown, as is the time from a normal endometrium progressing to hyperplasia. False-positive diagnoses of endometrial hyperplasia might be due to the sampling during natural regression, and false-negative diagnoses are possible when sampling is done during progression of benign or atrophic endometrium to hyperplasia.7 Untreated simple hyperplasia without atypia sometimes progress to carcinoma, and this risk might be greater with complex hyperplasia.8 Untreated hyperplasia with atypia is more likely to progress to endometrial cancer.8,9 Hyperplasia without atypia tends to spontaneously regress, whereas atypical hyperplasias are more likely to progress.10 Concomitant endometrial carcinoma is also more frequent in the presence of atypia. Unopposed moderate or high-dose oestrogen therapy in women with an intact uterus is associated with a significant increase in rates of endometrial hyperplasia, with increasing rates at longer duration of treatment and follow-up.11 In the 3-year PEPI trial,12 in 119 women randomised to 0·625 mg conjugated equine oestrogen daily, 74 (62%) developed some type of hyperplasia. In 119 women on placebo, 2081
Labelling salt in food: if yes, how? Common or table salt has been fought over, taxed (and therefore smuggled), and used in remuneration and as a political weapon, so important to daily life was this mineral. These days sodium chloride arouses passions of a different sort; it is widely seen as a threat to public health. With refrigeration and other means of food preservation, daily salt intake is now 9–11 g. But that is far too much, say various world and national authorities, who look to 5 or 6 g as a reasonable target. For example, the British Food Standards Agency has the goal of a one-third reduction, to 6·0 g by 2010.1 The UK’s Consensus Action on Salt and Health draws attention to dose-response calculations backing 3 g as something to aim for in future.2 That could, it is claimed, achieve a one-third drop in fatal strokes and a one-quarter reduction in mortality from ischaemic heart disease, which in the UK would translate to over 50 000 deaths prevented every year. If 3 g seems unrealistic, it is not that far below the 1·5 g sodium (3·75 g salt) suggested by the US National Heart, Lung, and Blood Institute3 4 years ago, on the basis of the then unpublished DASH [Dietary Approaches to Stop Hypertension]-Sodium results. The argument over the dangers of salt seems far from over, as responses to a cautious meta-analysis4 in the British Medical Journal in 2002 demonstrate. The multiplicity of Cochrane Library publications and updates on the salt/ hypertension debate 5–8 also shows what a controversial subject this remains. For one thing, rigorous randomised studies targeting large hypertensive or normotensive groups with serious reduction in salt intake over a long time are not easy to do. With the recent confident pronouncements they might even be impossible now. Another difficulty might be that the hoped-for effect on cardiovascular disease is an extrapolation from blood-pressure data. Fatal heart attacks and strokes have not been endpoints, or the numbers of such deaths have been too small to be revealing. Also controversial is the fact that the target is not just those with hypertension. The question, an old one in public health, is should population shifts in blood pressure be sought for the greater good even though not everyone will benefit? Another unresolved issue is the long-term effect of salt reduction; is there physiological adaptation over time, lessening blood-pressure differences in adults? This possibility makes confirmation of a study9 showing a programming effect, whereby salt restriction in infancy produces long-term blood-pressure lowering, all the more important. At least reducing salt intake to 6 g daily is unlikely to do harm. The Institute of Food Science and Technology has listed various recommendations from the 1990s on reference nutrient intakes and other forms of minimum daily requirement for sodium. These tend to be below the levels now being urged.10 The 2004 tables from the US Institute of Medicine include, for adults, an “adequate intake” equating www.thelancet.com Vol 364 December 11, 2004
to 3·75 g salt daily and an “upper limit” of 5·75 g.11 On Dec 8, 2004, the Institute of Medicine hosted in Washington, DC, a one-day symposium, looking at the triggers for a reexamination of a dietary reference intake. For sodium, perhaps a review is timely because the upper limit urged by some authorities and the adequate intake recommended by others are getting rather close. Also, at least for bread, the taste argument might not come into play until the reduction is more extreme than 25%.12 More such studies of how much salt can be removed before anyone notices and reaches for the compensatory salt grinder are needed. It is not unreasonable for public-health campaigns to continue, even though the debate is still alive. Those campaigns focus on three things: persuading retailers to stock less salty foods and manufacturers to lower the salt content of prepared foods; persuading the public to add less salt; and clear labelling of the salt content in items purchased. Since only 15–25% of intake is from a kitchen salt jar or added to the plate, most attention is being paid to what is on the shelves of retail outlets and on how those products are labelled. Salt producers in the USA and the UK might have kept the controversy on the boil13,14 but on the retail side there have been changes over several years. In the UK, some disappointment has been expressed at the reductions manufacturers are prepared to concede as a contribution to the government’s current target15 but there has been a downward trend. For example, bread contributes about one-sixth of daily salt intake. The British baking industry promises a 5% cut by the end of this year to add to the 12·5% and 10% reductions over the past two decades.16 If customers demand less salt, shops will want to stock such products and manufacturers will respond in turn, which brings us to labelling, which is not as easy as it sounds. One cereals manufacturer has a range of products, including individual portion packs for children. Six different packs in this range examined this month weighed 17–30 g and their sodium contents were 0·15–0·95 g per 100 g. So, if a child eats two different packs for breakfast the sums are not easy, and for a range of foodstuffs over a day they are tedious to the point of impossibility. So, is labelling a waste of time? No. Provided labels are not overloaded with information or confusing, the general rule that an informed consumer is better than an uninformed one holds. However, patients with heart problems need a lot of educational help with salt.17 Those perceiving themselves as healthy will probably need even more. Fortunately, there are different types of labelling to achieve the same end. Assuming that all sodium in the diet comes from table salt is a reasonable approximation and consumers will be more comfortable with figures for salt rather than sodium content. To think of servings or portions, rather than relying on arithmetic and grams per 100 g, sounds more like the real world, although servings 2079
Comment
Science Photo Library
Rights were not granted to include this image in electronic media. Please refer to the printed journal.
vary. Soups (along with bread and cereals, they contribute significantly to salt in our diets) can contain a lot of salt; a single bowl might carry 40% of the daily limit now recommended. However, labelling can be two-edged. One label on organic beans informs consumers that half a can will supply one of the UK government’s recommended five portions daily of fruit and vegetables. Containing “no artificial colours, preservatives, flavours or GM ingredients”, it sounds perfect. Hardly; one serving, the label also reveals, contains 2·5 g salt. Another method is Pick the Tick, a movement not restricted to Australasia but beginning there. Product endorsement needs careful handling but the Pick-the-Tick scheme appears to be well thought-out. It is not limited to salt. Basically, manufacturers pay for the right to display the logo if they meet content standards laid down by national heart foundations and monitored by independent laboratories. Customers look for the logo on a product and no longer need to squint at small type or reach for calculators. The scheme is having an effect18 but far more market penetration is required. In New Zealand, 33 tonnes of salt was removed from food items in a single year. Spread over 4 million New Zealanders the daily reduction would have had an imperceptible impact on blood pressure.19 Too many other factors involved in hypertension and cardiovascular disease (smoking, increased cholesterol, obesity, lack of exercise) are being tackled at the same time for it ever to be provable that a reduction in salt use as public policy has by itself saved lives. DASH-Sodium was an attempt to separate salt from other lifestyle changes in the senior trial. Demanding more DASH-Sodium data, a 2003 editorial by David McCarron argued that “If the quality of the diet is adequate, salt intake has little relevance to BP control for the vast majority of individuals”.20 Even in 2004 a review can still refer to salt reduction in the general population as contentious and to a “highly polarized divide” between those who support dietary salt reduction and those who oppose it.21 Given the arguments that earlier studies and systematic reviews have generated, the long2080
awaited13,20 DASH-Sodium details22 might not win over every doubter. Food labelling should include amount of salt (not sodium) per serving and per 100 g and at least a mention of the consensus maximum23 of, say, 6 g daily for adults, with suitable adjustment for products aimed at children. A simple mark of approval such as Pick the Tick, the US food guide pyramid, or the UK’s traffic light labels (a warning red for salt at 2·5 g per 100 g or more, an encouraging green for 0·25 g or less) would be a bonus, although care is needed lest the signals be internally confusing. The UK government wants to make healthy choices easier and rightly stresses the need for European agreement on simplified nutrition labelling, which would be mandatory for packaged foods.24 Public-health authorities seem impatient about salt but research on labels and on consumer preferences needs to be rigorous and not immune from the criticism that clinical and epidemiological studies of salt have faced and, arguably, survived.
David Sharp c/o The Lancet, London NW1 7BY, UK I declare I have no conflict of interest. 1
2 3
4
5 6
7 8
9
10 11
12 13
14
15
Food Standards Agency. Agency launches salt campaign. Sept 13, 2004. http://www.food.gov.uk/newsarchive/2004/sep/saltcampaignews (accessed Nov 2, 2004). He FJ, McGregor GA. How far should salt intake be reduced? Hypertension 2003: 42: 1093–99. National Institutes of Health. News release: NHLBI study shows large blood pressure benefit from reduced dietary sodium. http://www.nhlbi.nih.gov/ new/press/May17-00.htm (accessed Dec 7, 2004). Hooper L, Bartlett C, Davey Smith G, Ebrahim S. Systematic review of long term effects of advice to reduce dietary salt in adults. BMJ 2002; 325: 628. [See responses at: http://bmj.bmjjournals.com/cgi/eletters/325/7365/628 (accessed Dec 6, 2004)]. He FJ, McGregor GA. Effect of longer-term modest salt reduction on blood pressure. Cochrane Database Syst Rev 2004; 3: CD004937. Hooper L, Bartlett C, Davey Smith G, Ebrahim S. Advice to reduce dietary salt for prevention of cardiovascular disease. Cochrane Database Syst Rev 2004; 1: CD003656. Beard TC, Stowasser M. Cochrane and the salt debate. Lancet 2003; 362: 403. Jurgens G, Graudal NA. Effects of low sodium diet versus high sodium diet on blood pressure, renin, aldosterone, catecholamines, cholesterols, and triglyceride. Cochrane Database Syst Rev 2004; 1: CD004022. Geleijnse JM, Hofman A, Witteman JC, Hazebroek AA, Valkenburg HA, Grobbee DE. Long-term effects of neonatal sodium restriction on blood pressure. Hypertension 1997; 29: 913–17. Institute of Food Science and Technology. Current hot topics: salt. July 8, 2003: http//www.ifst.org/hottop17.htm (accessed Oct 26, 2004). Institute of Medicine. Dietary reference intakes (DRIs): recommended intakes for individuals, elements. Washington, DC: National Academy of Sciences, 2004. Girgis S, Neal B, Prescott J, et al. A one-quarter reduction in the salt content of bread can be made without detection. Eur J Clin Nutr 2003; 57: 616–20. Hanneman RL. Letter to Kathryn McMurry, HHS Office of Disease Prevention and Health Promotion. April 6, 2004. http://www.saltinstitute .org/pubstat/dgac-4-6-04.html (accessed Dec 2, 2004). Salt Manufacturers’ Association. Response of the Salt Manufacturers’ Association to the Salt Review of the Scientific Advisory Committee on Nutrition. Dec 23, 2002. http://www.saltsense.co.uk/releases/rel001.htm (accessed Dec 2, 2004). Food Standards Agency. Update on industry salt reduction activity— September, 2004. London: Food Standards Agency, 2004.
www.thelancet.com Vol 364 December 11, 2004
Comment
16 17
18
19
Federation of Bakers. The baking industry: salt. http://www.bakers federation.org.uk/salt.aspx (accessed Dec 2, 2004). Neily JB, Toto KH, Gardner EB, et al. Potential contributing factors to noncompliance with dietary sodium restriction in patients with heart failure. Am Heart J 2002; 143: 29–33. Williams P, McMahon A, Boustead R. A case study of sodium reduction in breakfast cereals and the impact of the Pick the Tick food information programme in Australia. Health Promot Int 2003; 18: 51–56. Young L, Swinburn B. Impact of the Pick the Tick food information programme on the salt content of food in New Zealand. Health Promot Int 2002; 17: 13–19.
20 21 22
23
24
McCarron DA. DASH-sodium trial: where are the data? Am J Hypertension 2003; 16: 92–94. O’Shaughnessy KM, Karet FE. Salt handling and hypertension. J Clin Invest 2004; 113: 1075-81. Bray GA, Vollmer WM, Sacks FM, et al. A further subgroup analysis of the DASH diet and dietary sodium levels on blood pressure: results of the DASH-Sodium Trial. Am J Cardiol 2004; 94: 222–27. Consensus Actino on Salt and Health. Salt and sodium labelling of food. http://www.hyp.ac.uk/cash/information/salt_labelling.htm (accessed Dec 2, 2004). HM Government/Department of Health. Choosing health: making healthy choices easier (Cm 6374). London: Stationery Office, 2004.
Phyto-oestrogens and the endometrium
www.thelancet.com Vol 364 December 11, 2004
Rights were not granted to include this image in electronic media. Please refer to the printed journal. Science Photo Library
Vittorio Unfer and colleagues1 recently reported a 5-year randomised double-blind study on the endometrial effects of the use of soy phyto-oestrogen in postmenopausal women. Of 154 patients receiving 150 mg isoflavones a day for 5 years, six (4%) developed endometrial hyperplasia (five simple, one complex; no endometrial hyperplasia with atypia), compared with none of 165 patients on placebo. The same group2 also reported a randomised trial of highdose phyto-oestrogens added to clomiphene citrate, to reverse the antioestrogenic effects of clomiphene on the endometrium during intrauterine insemination. The endometrium was thicker, miscarriage rates lower, and ongoing pregnancy rate higher in patients on phyto-oestrogen plus clomiphene than in those on clomiphene alone. These findings are neither surprising nor alarming, confirming what we know about phyto-oestrogens acting as a selective oestrogen-receptor modulator (SERM).3 Soy phyto-oestrogens (isoflavones genistein, daidzin, and glycitin) induce endometrial stromal-cell proliferation in vitro.4 The proliferative effect occurred at high concentrations and was 8–15% lower than that induced by oestradiol. In the presence of oestradiol, however, the isoflavones antagonised the proliferative effect of oestradiol by 10–20%, which indicates that isoflavones are weak oestrogens and their antioestrogenic effects are only seen in high concentrations when combined with physiological concentrations of oestradiol. Animal models also show that high doses of isoflavones, particularly genistein, stimulate uterine growth and expression of several genes regulated by uterine oestrogen, and isoflavones have weak oestrogenic activity in mammary gland and hypothalamic/pituitary cells. Any clinical application of these findings might result in different outcomes, possibly due to various doses and preparations used for isoflavones and individual differences in metabolism. A 4-week study of soy-supplemented diet in postmenopausal women did not have oestrogenic effects in liver and pituitary-gland function.5 In a small randomised trial, 25 mg soy-protein isolate daily with 120 mg isoflavones added to oestradiol for 6 months did not protect endometrium from oestradiol-induced hyperplasia.6
The natural history of endometrial hyperplasia is not fully understood and some simple and complex hyperplasias will regress without treatment.7 However, the time over which regression occurs is unknown, as is the time from a normal endometrium progressing to hyperplasia. False-positive diagnoses of endometrial hyperplasia might be due to the sampling during natural regression, and false-negative diagnoses are possible when sampling is done during progression of benign or atrophic endometrium to hyperplasia.7 Untreated simple hyperplasia without atypia sometimes progress to carcinoma, and this risk might be greater with complex hyperplasia.8 Untreated hyperplasia with atypia is more likely to progress to endometrial cancer.8,9 Hyperplasia without atypia tends to spontaneously regress, whereas atypical hyperplasias are more likely to progress.10 Concomitant endometrial carcinoma is also more frequent in the presence of atypia. Unopposed moderate or high-dose oestrogen therapy in women with an intact uterus is associated with a significant increase in rates of endometrial hyperplasia, with increasing rates at longer duration of treatment and follow-up.11 In the 3-year PEPI trial,12 in 119 women randomised to 0·625 mg conjugated equine oestrogen daily, 74 (62%) developed some type of hyperplasia. In 119 women on placebo, 2081