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Long term gluten consumption in adults without celiac disease and risk of coronary heart disease: prospective cohort study

BMJ 2017; 357 doi: https://doi.org/10.1136/bmj.j1892 (Published 02 May 2017) Cite this as: BMJ 2017;357:j1892

Letter to the editor: Are gluten-free diets among people without celiac disease „mass murder“? Re: Long term gluten consumption in adults without celiac disease and risk of coronary heart disease: prospective cohort study

Dear Sir.

We challenge the conclusions of the recent study by Lebwohl, et al (1) which reported that while long-term dietary gluten consumption in people without coeliac disease may not be related to heart disease risk, "the avoidance of gluten may result in reduced consumption of beneficial whole grains, which may affect cardiovascular risk." Their statements, which have led to a rapid spread of misinformation on social media, can be challenged from several perspectives.

Firstly, although the conclusions of the authors may appear compatible with the results of recent meta-analyses, they failed to mention that not all studies reported a clear association between cereals and cardiovascular risk.(2) Furthermore, in some studies, the associations were primarily due to a higher intake of other foods such as fruits, especially citrus, cruciferous vegetables, nuts, or occurred only in men. Moreover, randomized controlled trials (RCTs), which are usually considered to provide evidence on a cause-effect relation, on whole-grain intake and risk markers of diseases have provided less consistent results.(3,4) Interestingly, in one of the first RCTs, there was no evidence of any benefit of increased cereal fibre intake and mortality was somewhat higher although not statistically significant.(5)

Secondly, despite the biological plausibility of the protective effect of cereals on risk of cardiovascular diseases, there are many potential mechanisms through which cereals may act on individual risk factors. In this regard, the authors overlooked that it is possible to get plenty of fibre and various important nutrients from gluten-free grains, such as brown rice, corn, oats, sorghum, millet or pseudo-cereals like amaranth, buckwheat, quinoa. Also, in addition to fibre, many other potentially beneficial compounds within high fibre non-cereal foods, such as antioxidants, hormonally active lignans, phytosterols, amylase inhibitors and saponins could be responsible for their health benefits.

Thirdly, the authors overlooked the low prevalence of cardiovascular diseases in some societies that are 'horticultural' and rely on roots and tubers, as opposed to cereal grains. Indeed, studies in Okinawans, Kitavans, South American Tsimane, whose diets are based on sweet potatoes, plantain, manioc, and only small amount of rice or corn are reported to have extremely low prevalence of cardiovascular diseases.(6,7) Moreover, Okinawan seniors not only have the highest life expectancy in the world, but also the highest health expectancy. However, the traditional diets of these societies underwent „Westernisation“ i.e. an increase consumption of sugar, cereals, processed foods and, in the case of Okinawans, „Japanisation“ (an increase in white rice). All these changes are thought to be the cause of remarkable health deterioration. A typical example is the South Pacific island of Western Samoa, which saw a dramatic explosion of the prevalence of obesity and non-insulin dependent diabetes mellitus, associated with high leptin concentrations.(8)

Fourthly, it has been suggested that some environmental factors specific to agrarian societies could initiate diseases of affluence in the above mentioned societies. Although there are many such candidate environmental factors, cereals seem to be the clearest defining dietary difference between an agrarian and non-agrarian diet. As for the constituent(s) of cereals causing leptin resistance as a sign of insufficient adaptation, Jönsson et al (9) propose lectins such as wheat germ agglutinin as a candidate with sufficient properties. Indeed, several lines of evidence suggest that cereal lectins could cause leptin resistance either indirectly, through effects on metabolism central to the proper functions of the leptin system, and/or directly, through binding to human leptin or leptin receptor, thereby affecting the function.(9)

Fifthly, the hypothesis that an agrarian diet could initiate diseases of affluence was tested in prospective diet interventions comparing Paleolithic diet with non-agrarian diets. These studies have shown beneficial effects of Paleolithic diet comprising lean meat, fruits, vegetables and nuts, and excluding food types, such as dairy, legumes and cereal grains, compared with other healthy diets, on various health markers. A recent systematic review and meta-analysis, where these studies were included, showed that a Paleolithic diet improves some components of the metabolic syndrome more than guideline-based control diets.(10) Another systematic review and meta-analysis concluded that the Mediterranean diet with education decreased HbA1c more than control diets but not more than the Palaeolithic diet with education.(11)

Finally, the absence of cardiovascular benefit of strict gluten-free diet observed in study by Lebwohl et al.(1) can be explained by other factors. For example, it is generally agreed that even among patients with celiac disease up to 60% are partially non-adherent (12). Moreover, individuals following a gluten free diet because of gluten sensitivity or another health-related reason were found to have significantly lower dietary adherence than those diagnosed with celiac disease as defined by the Biagi et al dietary adherence score.(13) It is also important to note that some foods such as fish and rice, consumed by people on gluten free diet have high concentrations of metals such as arsenic, mercury, lead, cadmium, and cobalt and the association between these metals and cardiovascular disease has been recognised for years as highlighted in a recent review by Lamas et al.(14)

In summary, the current ethnographic, epidemiologic and prospective data suggest that a well-balanced gluten-free diet should not necessarily put people without coeliac disease at a higher risk for cardiometabolic diseases. Indeed, hominins consumed a grain-free diet from 2.6 million years ago to about 12,000 years ago (15), so it is highly unlikely that a gluten-free diet or Paleolithic diet is going to kill anyone long-term. In fact, grains are not essential, and contain no nutrient that cannot be obtained from other plant foods. Thus, it can be safely concluded that, whether gluten-free diet is indicated or not, it is not detrimental to avoid gluten. However, it is also important to note that recent scientific findings are beginning to lend support to a new approach to diet, science-backed "personalised" approaches to dietary recommendations. Available data warrant additional evaluations of the risks and benefits of gluten avoidance among specific groups of non-celiac population.

Michal R. Pijak, MD
Kristina Szantoova, PhD
Jan Vyjidak, LLM. MSc.

References

1. Lebwohl B, Cao Y, Zong G, et al. Long term gluten consumption in adults without celiac disease and risk of coronary heart disease: prospective cohort study. BMJ 2017;357:j1892. doi: 10.1136/bmj.j1892.
2. Aune D, Keum N, Giovannucci E, et al. Whole grain consumption and risk of cardiovascular disease, cancer, and all cause and cause specific mortality: systematic review and dose-response meta-analysis of prospective studies. BMJ 2016;353:i2716. doi: 10.1136/bmj.i2716.
3. Brownlee IA, Moore C, Chatfield M, et al. Markers of cardiovascular risk are not changed by increased whole-grain intake: the WHOLEheart study, a randomised, controlled dietary intervention. Br J Nutr. 2010 Jul; 104(1): 125–134. doi: 10.1017/S0007114510000644
4. Tetens I. Substituting whole grain for refined grain: what is needed to strengthen the scientific evidence for health outcomes? Am J Clin Nutr 2017;105:545-46. doi:10.3945/ajcn.117.152496.
5. Burr ML, Fehily AM, Gilbert JF, et al. Effects of changes in fat, fish, and fibre intakes on death and myocardial reinfarction: diet and reinfarction trial (DART). Lancet 1989;2:757-61. doi:org/10.1016/S0140-6736(89)90828-3.
6. Lindeberg S, Söderberg S, Ahrén B, Olsson T. Large differences in serum leptin levels between nonwesternized and westernized populations: the Kitava study. J Intern Med. 2001;249:553-8. doi:10.1046/j.1365-2796.2001.00845.x
7. Kaplan H, Thompson RC, Trumble BC et al. Coronary atherosclerosis in indigenous South American Tsimane: a cross-sectional cohort study. Lancet 2017;389(10080):1730-1739. doi: 10.1016/S0140-6736(17)30752-3.
8. Zimmet P, Hodge A, Nicolson M, et al. Serum leptin concentration, obesity, and insulin resistance in Western Samoans: cross sectional study. BMJ 1996; 313: 965–9. doi:.org/10.1136/bmj.313.7063.965.
9. Jönsson T, Olsson S, Ahrén B, Bøg-Hansen TC, Dole A, Lindeberg S. Agrarian diet and diseases of affluence--do evolutionary novel dietary lectins cause leptin resistance? BMC Endocr Disord. 2005;10:5-10 doi: 10.1186/1472-6823-5-10.
10. Manheimer EW, van Zuuren EJ, Fedorowicz Z, Pijl H. Paleolithic nutrition for metabolic syndrome: systematic review and meta-analysis. Am J Clin Nutr 2015;102:922–32. doi: 10.3945/ajcn.115.113613.
11. Carter P, Achana F, Troughton J, Gray LJ, Khunti K, Davies MJ. A Mediterranean diet improves HbA1c but not fasting blood glucose compared to alternative dietary strategies: a network meta-analysis. J Hum Nutr Diet 2014;27:280–97. doi: 10.1111/jhn.12138.
12. Hall NJ, Rubin G, Charnock A. Systematic review: adherence to a gluten-free diet in adult patients with coeliac disease. Aliment Pharmacol Ther. 2009;30(4):315-30.
13. Biagi F, Bianchi PI, Marchese A, et al. A score that verifies adherence to a gluten-free diet: a cross-sectional, multicentre validation in real clinical life. Br J Nutr. 2012 Nov 28;108:1884-8.
14. Lamas GA, Navas-Acien A, Mark DB, Lee KL. Heavy Metals, Cardiovascular Disease, and the Unexpected Benefits of Chelation Therapy. J Am Coll Cardiol. 2016;67:2411-8. doi: 10.1016/j.jacc.2016.02.066.
15. Eaton SB, Konner MJ, Shostak M. Stone Agers in the Fast Lane: Chronic Degenerative Diseases in Evolutionary Perspective. Am J Med. 1988;84:739–49.

Competing interests: No competing interests

12 May 2017
Michal R. Pijak
Assistant Professor of Internal Medicine
Kristina Szantoova, PhD, Jan Vyjidak, LLM. MSc.
1st Department of Internal Medicine, Slovak Medical University, Teaching Hospital of Academician L. Dérer, Limbova 5, 833 05 Bratislava, Slovakia