Letter To The Editor-bmj

Letter to the Editor- In –Chief, British Medical Journal While reviewing the literature on nutrition in diabetes mellitus, we have just recently studied Mann et al’s “Evidence based nutritional approaches to the prevention and treatment of diabetes mellitus” (1). A superficial glance at the article immediately raised questions, because the endpoints referred to were mostly weight control and LDL. Since the DCCT (2) and UKPDS (3) studies define glycemic control expressed as HbA1c, as the most reliable predictor for endpoints such as mortality, blindness, amputation or dialysis, why were not studies exploring the effect of diet on glycemic control referred to? It also appeared strange that the authors only quoted LDL levels, in studies also reporting other risk factors, such as total cholesterol, HDL, ratios and triglycerides. Therefore we undertook a more thorough analysis, comparing claims of evidence on a few but central statements, with the results and texts of the articles referred to, including also these above mentioned diabetes and cardiovascular risk factors. We also performed a search to see if relevant studies present prior to the publication of Mann et al had been omitted from citing. The results are in brief shown below. On saturated fats Mann et al. claim: “There is convincing evidence from meta analyses of controlled trials in those without diabetes [4-6] that an exchange of dietary saturated fatty acids with unsaturated fatty acids (other than trans fatty acids - see below) or carbohydrates will reduce LDL-cholesterol.” Howell et al’s meta analysis reveals that the magnitude of this difference in LDL by the consumption of saturated fat, as compared to the recommended diet is only marginal, around 5% (5). If drugs like statins would reduce LDL by only 5%, would they be prescribed or even approved, especially if they caused a more prominent deterioration of other risk factors? Katan et al are in fact warning:”If any fat is replaced by carbohydrates, fasting triglyceride values rise and HDL concentrations fall; effects on LDL depend on the type of fat that is being replaced. ” (4) Replacing saturated fats with carbohydrates leads to an increase in other cardiovascular risk factors, according to this study, while LDL is marginally affected. Mensink et al state:” The introduction of low-fat, high-carbohydrate foods in the United States does not appear to have reduced caloric intake; rather, carbohydrates seem to have been added to existing intakes. However, further studies on the long-term effect of high-carbohydrate diets on body weight are urgently needed” (6). These authors are questioning if high carbohydrate diets are healthy also on the basis of deteriorating total:HDL cholesterol ratios and are suspicious of the absence of relevant studies on the diet advocated by Mann et al. Three relevant studies on saturated fats in the form of milk fats were not cited. Vessby, co-author in Mann et al was a co-author of all three: A prospective case-control study, showed that estimated intake of milk fat is negatively correlated to cardiovascular risk

factors, and does not increase the risk of a first myocardial infarction (7), another that milk fat is associated with a more favorabel LDL particle distribution (8), and a third that milk fat is negatively associated with abdominal obesity (9), also well-known cardiovascular risk factors. None of these studies support the hypothesis that saturated fats should be reduced, at least not from milk products; rather it gives evidence for the contrary. Regarding poly-unsaturated fats Mann et al. claim: “Substituting PUFA for saturated fatty acids has beneficial effects on serum lipid levels and lipoprotein concentration and composition [4-6] and insulin sensitivity [10]”. Refs 4-6 are dealt with above. Summers et al (10) is a trial involving 17 people, thereof only six diabetics, and within this group there was no significant improvement in insulin sensitivity in contrast to the claims above. However, another paper by two of the co-authors in Mann et al., Vessby and Karlstrom, was not quoted. (11). It is a small but well performed study of 15 diabetics in a metabolic ward, with a crossover design revealing significantly deranged glycemic control, within the end of the three week trial period when a low fat PUFA diet was served instead of a low fat saturated fat diet. On low carbohydrate diets Mann et al. state: “There is no long-term evidence of benefit of low or very low carbohydrate diets. Such diets would be undesirably high in fat and could increase body weight and decrease insulin sensitivity [12-14]. Low carbohydrate, high fat diets have not been shown to achieve longterm weight loss [15, 16].” But Vessby et al (12) and Toeller et al (13) do not evaluate low carbohydrate diets, whereas Shah et al (14) is a review, not an original paper, stating: “During overfeeding, excess fat intake is stored as fat, whereas excess carbohydrate is mostly oxidized in the short term but can lead to substantial gain in fat stores because of reduced fat oxidation and considerable de novo lipogenesis in the long term..”, thus describing the metabolic features of hyperinsulinism by high carbohydrate diets. They conclude: “ a high-monounsaturated fat diet to control glycemic control and lipoprotein levels in patients with diabetes should not affect weight loss or maintenance, provided that energy intake is carefully controlled.”. Most remarkable is that Mann et al. are not mentioning the results, of the two articles they cited as evidence of absence of long-term studies on low carbohydrate diets. Both Foster (15) and Samaha (16) do report lasting weight loss, improved insulin sensitivity in both diabetics and the obese, reduced triglycerides and the absence of LDL elevation with high fat low carbohydrate diets. Therefore none of Mann et al’s statements on such diets in diabetes or obesity were supported by evidence, with the only exception that only short-term studies existed at the time for publishing. Indeed, although very few prospective clinical trials were present on the issue of diabetes diet on glycemic control at the time Mann et al was published; at least two existing papers were not quoted (17-18). Both reported a detrimental effect of the current low fat high carbohydrate recommendations on glycemic control, as compared to older more fat lesser carbohydrate diets Even more, Mann et al. failed to report any prospective randomized trial in diabetics or the obese, showing that the current low fat high carbohydrate recommendations in diabetes resulted in improved glycemic control, substantial weight reduction, or

improvement of blood lipids when more than LDL is considered,. Neither are we aware of the existence of such studies. Finally the readers must ask themselves, how could this paper become accepted in a peer reviewed journal? This is indeed shocking: Mann et al. never needed peer reviewing. The Editor-in-Chief of the journal it was published in, Nutrition, Metabolism and Cardiovascular Disease, Elsevier Publications, is one of the coauthors. Needless to say, these authors have not declared their conflicts-of-interest. It is a documented fact that one of the authors for more than a decade had his professorship paid for by food companies, mainly producers of margarine, frying fats high in trans fats and sugar.

Malmoe 2007-08-24

Ralf Sundberg, MD, Ph.D., former Associate Professor of Transplant Surgery, Karolinska Institute , Stocholm, Sweden. Johan Hedbrant, Research Engineer, Linköping University, Linköping Sweden Address for correspondence: Ralf Sundberg Bodilsgatan 6 SE-217 74 Malmoe Sweden [email protected]

References 1: Mann JI, De Leeuw I, Hermansen K, Karamanos B, Karlstrom B, Katsilambros N, Riccardi G, Rivellese AA, Rizkalla S, Slama G, Toeller M, Uusitupa M, Vessby B; Diabetes and Nutrition Study Group (DNSG) of the European Association (2004) Evidence-based nutritional approaches to the treatment and prevention of diabetes mellitus. Nutr Metab Cardiovasc Dis 14(6):373-94 2. The Diabetes Control and Complications Trial Research Group (1993) The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 329(14):977-86.

3. Stratton IM, Adler AI, Neil HA, Matthews DR, Manley SE, Cull CA, Hadden D, Turner RC, Holman RR (2000) Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ 321(7258):405-12 4. Katan MB, Zock PL, Mensink MP (1995) Dietary oils, serum lipoproteins, and coronary heart disease. Am J Clin Nutr 61:1368S-1373S 5. Howell WH, McNamara D J, Tosca MA, Smith BT, Gaines JA (1997) Plasma lipid and lipoprotein responses to dietary fat and cholesterol: meta analysis. Am J Clin Nutr 65:1747-1764 6. Mensink RP, Zock PL, Kester ADM, Katan MB (2003) Effects of dietary fatty acids and carbohydrates on the ratio of serum total to HDL-cholesterol and on serum lipids and apolipoproteins: a meta-analysis of 60 controlled trials. Am J Clin Nutr 77:11461155 7 Warensjo E, Jansson JH, Berglund L, Boman K, Ahren B, Weinehall L, Lindahl B, Hallmans G, Vessby B.(2004)..:Estimated intake of milk fat is negatively associated with cardiovascular risk factors and does not increase the risk of a first acute myocardial infarction. A prospective case-control study. Br J Nutr. 2004 Apr;91(4):635-42. .8 Sjogren P, Rosell M, Skoglund-Andersson C, Zdravkovic S, Vessby B, de Faire U, Hamsten A, Hellenius ML, Fisher RM (2004) Milk-derived fatty acids are associated with a more favorable LDL particle size distribution in healthy men. . J Nutr. 2004 Jul;134(7):1729-35 9 Rosell M, Johansson G, Berglund L, Vessby B, de Faire U Vessby B, Uusitupa M, Hermansen K, et al (2001) Associations between the intake of dairy fat and calcium and abdominal obesity.Int J Obes Relat Metab Disord. 2004 Nov;28(11):1427-34. 10. Summers LKM, Fielding BA, Bradshaw HA, et al (2002) Substituting dietary saturated fat with polyunsaturated fat changes abdominal fat distribution and improves insulin sensitivity. Diabetologia 45:369-377 11. Vessby B, Karlstrom B, Boberg M, Lithell H, Berne C (1992) Polyunsaturated fatty acids may impair blood glucose control in type 2 diabetic patients. Diabet Med 1992 9(2):126-33. 12. Vessby B, Uusitupa M, Hermansen K, et al (2001) Substituting dietary saturated fat with monounsaturated fat impairs insulin sensitivity in healthy men and women: the KANWU Study. Diabetologia 44:312-319 13. Toeller M, Buyken AE, Heitkamp G, Cathelineau G, Ferriss JB, Michel G, and the EURODIAB IDDM Complications Study Group (2001) Nutrient intakes as predictors of body weight in European people with type I diabetes. Int J Obes 25:1815-1822

14. Shah M, Garg A (1996) High fat and high carbohydrate diets and energy balance: a review. Diabetes Care 19:1142-1152 15. Foster GD, Wyatt HR, Hill JO, et al (2003) A randomized trial of a lowcarbohydrate diet for obesity. N Engl J Med 348: 2082-2090 16. Samaha FF, Iqbal N, Sheshadri P, et al (2003) A low-carbohydrate as compared with a low-fat diet in severe obesity. N Engl J Med 348:2074-2081 17 McCulloch DK, Mitchell RD, Ambler J, Tattersall: A prospective comparison of “conventional” and high carbohydrate/high fibre/low fat diets in adults with established Typ 1 (insulin-dependent) diabetes. Diabetologia(1985)28:208-12 18 Coulston AM, Hollenbeck CB, Swislocki AL, Reaven GM.. Persistence of hypertriglyceridemic effect of low-fat high-carbohydrate diets in NIDDM patients. Diabetes Care 1989 Feb;12(2):94-101