The Science of Diets March Edition 2022
Introduction Have you ever thought about dieting? Most people think about it to lose weight in order to keep the body healthy, decrease risks of complications or reach one’s desired appearance. In the past years, various diet plans have been invented. A current wellknown diet plan is intermittent fasting. In this edition, you will find out about the meaning of intermittent fasting, the different types and its effect on human health. Besides dieting for previously mentioned reasons, diets could also be implemented for diseases such as gluten-free diets for celiac patients. Read further to discover why this special diet is efficacious in this particular patient population. Lastly, this edition will shed light on the high-fat, low-carbohydrate, ketogenic diets and their effect on the human body. Enjoy reading!
Yong Xin Cao Science Coordinator 2021/2022 SFD Lithuania Established in the year 1926, Studentų Farmacininkų Draugija (SFD) (Pharmacy Students Association) in Lithuania, continues to bring Lithuanian pharmacy students together, providing them with interpersonal and professional development opportunities as well as educating the public about pharmaceuticals, pharmacoepidemiology and public health.
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Intermittent fasting For thousands of years, beginning with philosophers like Hippocrates, Socrates and Plato, fasting was recommended for health reasons and the clarity of mind. However, when the article in 2018, published in the prestigious journal “Cell Metabolism” by the scientists from the National Institute on Aging (NIA) at the National Institutes of Health in the US, with 292 mice subjects, concluded that increasing time between meals made mice healthier overall and live longer compared to mice who ate more frequently, the real interest has been piqued, launching the cascade of research endeavours about various forms of calorie restriction for humans in a pursuit to figure out the most robust longevitypromoting eating regimen. WHAT IS FASTING? The term “fasting” is described as “going for a certain length of time without eating anything” or “abstaining from food”. The timing of meals matters more than the composition of the food consumed. The term “food” means anything that contains calories, thus the only things that don’t count are water, unsweetened tea and coffee. There are different kinds of fasting, generally, they all restrict the time during which one can eat, resulting in a lower overall calorie intake. The different types of restricted eating, according to a renowned American doctor, Peter Attia MD, are: •
Overnight fasting – is what everybody experiences naturally during the night, it’s a gap between dinner and breakfast. If one eats dinner at 7 pm and breakfast at 9 am one has undergone a 14-hour fasting. • Time-restricted feeding – increasing that window from just an overnight fast to a slightly longer window. It can be anything from 12/12, 14/10, 16/8 – the first number refers to a duration spent with no nutrient exposure followed by the time frame in which one would be able to consume food without restriction. • Alternate day fasting – a type of eating when one alternates between the usual ad libitum (lat. “to one’s pleasure”) diet every other day and restricting calorie intake to typically 400 to 600 calories or abstaining from calories whatsoever on other days. • Intermittent fasting – the term that has gained popularity, however, it is usually misused by being confused with time-restricted feeding, the most common being 16/8. Ideally, this term is supposed to refer to periodic fasting - abstaining from food every week/month/quarter for more than 36 hours. • 5/2 diet – a relatively widespread approach to fasting, when 5 days of the week a person eats ad libitum and 2 other days restricts calories to typically 400 to 600 calories per day. As a rule of thumb, it shouldn’t be two consecutive days. • Prolonged (multiple-day) fasting – from a clinical perspective it is a 3-7 day “water only”, although still including tea, coffee and some minerals, fasting. One can opt for any restricted feeding strategy as long as it generally results in a reduced calorie intake. However, it has been observed that intermittent fasting is easier for EPSA – European Pharmaceutical Students’ Association
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people to sustain than other eating regimens such as reducing portion sizes. Thus, intermittent fasting is a more feasible long-term alternative that helps to optimise health and longevity. WHAT ARE ITS KNOWN EFFECTS ON HUMAN HEALTH? There are multiple reasons to consider some form of fasting, which include but are not limited to: • Reductions in visceral fat mass1 that is linked to heart diseases and certain cancers2; • Used as a complementary approach to improving mental clarity for patients with multiple sclerosis3 and prevention of brain degenerative diseases4; • Enhanced mitochondrial health, DNA repair and autophagy5, therefore reduced chances of cancer, increased energy levels and overall contributed to faster cell turnover; • Slowed ageing process due to free radical damage6 since eating less means experiencing less oxidative stress; • Increased Human Growth Hormone (HGH) levels significantly7, therefore helping to build the muscle and repair vital tissues; • Prevented carcinogenesis8 by activating sirtuins (proteins that influence cellular processes like ageing, transcription, apoptosis, inflammation9) that alter gene expression and metabolic homeostasis; • Improved alertness, mood and subjective feelings of well-being, possibly improving overall symptoms of depression10; • Caloric restriction without malnutrition upregulates cell repair pathways slowing the ageing process and extending lifespan11; • Statistically significantly increased insulin sensitivity and reduced blood plasma triglycerides12 are linked to cardiovascular events. Caloric restriction has consistently been shown to extend life span and ameliorate ageing-related diseases, also known as increasing health span13. In one review article researchers even summarised the effects of Dietary Restriction (DR) and Intermittent fasting (IF) and presented them by taking Da Vinci's Man as a paragon of humanity. The picture shows how DR-IF has a positive impact on many organ systems, from macro – the CNS, blood composition, internal organs, to micro – enzyme regulation and favourable modulation of inter- and intra- cellular pathways.
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Figure 1: Changes for healthy ageing mediated by Dietary restriction and Intermittent fasting In conclusion, some form of eating restriction without malnutrition can be beneficial for most people, because it is first and foremost easier to sustain than other types of diets, secondly provides bouquet of health benefits, from improved lipid metabolism to a positive impact on one’s mental health to favourable processes on the cellular level. Therefore, if adopted correctly, intermittent fasting is a way to enhance one’s physical and mental well-being at the moment and in the long term.
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Gluten-free diet A gluten-free diet has been popularised over the last two decades. Celiac disease was first described in 1888 by Samuel Gee, but only in 1953, did the importance of gluten in the origin of this pathology become clear16. Considering the fact that only around 1% of people have conditions such as celiac disease, sales of gluten-free foods have skyrocketed to $15.5 billion in 2016 in the United States alone22. However, there is confusion about whether gluten is bad only for people with diagnosed celiac disease and intolerance or whether anyone would benefit from quitting gluten. To begin with, it’s important to understand what gluten is. Gluten is a collective compound that consists of a group of proteins – prolamins – found in wheat, barley, rye, and triticale14. Various forms of these proteins exist, but wheat mostly contains gliadin and glutenin, while barley mainly contains hordein. Gluten is being added to many foods due to its technological properties – it’s sticky and elastic, increasing strength, rise and smoothness of baked goods and “ready-to-eat” meals. Moreover, it’s crucial to differentiate between different gluten and wheat ingestion related conditions. Celiac disease is a genetically predisposed gluten-induced immune-mediated enteropathy characterised by a specific genetic genotype (HLA-DQ2 and HLA-DQ8 genes) and autoantibodies (anti-tissue transglutaminase and anti-endomysial). Prolamins contain critical epitopes presented by either HLA-DQ2 or HLA-DQ8 serotypes and induce a CD4+ T-lymphocytes response. It has been ascertained that gliadin triggers the disassembling of enterocyte tight junctions (TJs) rendering intestinal epithelia permeable to macromolecules. Gliadin peptides passing through the lamina propria, activate CD4+ T-lymphocytes that produce high levels of pro-inflammatory cytokines, inducing a T-helper pattern, which causes a clonal expansion of B-lymphocytes that subsequently differentiate in plasma-cells secreting anti-gliadin and anti-tissue-transglutaminase antibodies17. Although the inflammatory process specifically targets the intestinal mucosa, patients may present with gastrointestinal signs or symptoms, such as diarrhoea, bloating and constipation, extraintestinal signs and symptoms, such as fatigue, anaemia, dermatitis or joint pain, or both, suggesting that celiac disease is a systemic disease15. On the other hand, non-celiac gluten sensitivity (NCGS), the pathogenesis of which is largely unknown, is diagnosed in individuals who do not have celiac disease or wheat allergy but who have intestinal symptoms related to ingestion of gluten-containing grains, which subside upon withdrawal. Compared to NCGS, celiac disease patients have to be monitored more closely due to possible nutritional deficiencies and the development of possible comorbidities, because due to inflammation in the intestines the villi get damaged, leading to various malabsorption syndromes15. Celiac disease is diagnosed by either a biopsy, in which a reduction in intestinal villi is apparent, or by using serological assays for IgA anti-tissue transglutaminase (TGA) and IgA anti-endomysial (EMA).
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Figure 2: Pathology of celiac diseases Many patients blame gluten for being the cause of their Irritable Bowel Syndrome (IBS), however, instead of gluten-free, a so-called FODMAP diet (low in fats, carbohydrates, gluten, or fermented oligosaccharides, disaccharides, monosaccharides, and polyols) has proven to be more effective at alleviating symptoms, such as repeated abdominal pain and changes in bowel movements, which may lead to diarrhoea, constipation, or both18. The mechanism behind the FODMAP foods is that in the small and large intestine, EPSA – European Pharmaceutical Students’ Association
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the small FODMAP molecules exert an osmotic effect, which means more fluid is drawn into the bowel. FODMAPs are also rapidly fermented by colonic microflora producing gas. The increase in fluid and gas distends the bowel. When it comes to other benefits of the gluten-free diet (GFD), some patients self-report practising GFD for rheumatoid arthritis, treatment of autism and psychiatric disorders, as well as enhancement of athletic performance19, although the evidence on the latter has been scarce and inconclusive20. It has been hypothesised that the factor that causes individuals on a GFD to feel better is not the absence of gluten itself, but the reduction in consumption of highly processed and high glycaemic index foods, such as pastries, bread and pasta21. In conclusion, celiac disease, non-celiac gluten sensitivity (NCGS) and IBS are different conditions that are being diagnosed and treated differently. For people with celiac disease and NCGS the best treatment and management to this day is total avoidance of gluten-containing grains, whereas, for people who do not qualify for such diagnosis and have IBS instead, a FODMAP diet is proven to be effective. To date there is not much evidence that GFD has a significant effect on people who do not have celiac disease or non-celiac gluten sensitivity (NCGS), however, research suggests that reducing the intake of highly processed food, with or without gluten, might improve subjective and objective health metrics.
Author: Nida Abraityte, a 4th year pharmacy student at Lithuanian University of Health Sciences.
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What do we know about a ketogenic diet? The ketogenic diet was firstly introduced in 1920 as a treatment for refractory epilepsy. It is described as a diet that restricts carbohydrate intake to less than 20 g/day (Figure 1). This results in inducing fat-burning to produce ketosis23. Currently, its efficacy for the treatment of other diseases such as obesity, cancer, cardiovascular or respiratory diseases is still being tested23. A traditional diet consists of approximately 55% carbohydrates, 30% of fat and 15% of proteins, however, the use of the ketogenic diet mimics fasting, which can suppress hunger and significantly reduce carbohydrates24. This diet was originally mainly composed of long-chain fatty acids. Nevertheless, it was difficult to follow it, especially for the long-term, therefore, a more attractive variety of this diet was developed. Nowadays, it can be either based on medium-chain triglycerides or on the modified Atkins diet (protein content is not changed, only carbohydrates intake is reduced while fat – increased)2. During the ketogenic diet fatty acids in the liver, heart, gastrointestinal tract and kidneys are oxidised to produce ketone bodies (mainly acetoacetate, βhydroxybutyrate and acetone), which then can be used as a predominant source of energy25. Usually, after 3 days of the ketogenic diet, 30 – 40% of total energy can be received from ketones, although brain tissue can obtain 60 – 70% of its energy only from ketones25. However, it is important to mention that the ketogenic diet is contraindicated for pregnant women, patients with kidney failure or cardiac arrhythmia and older people with frailty26. Side effects of this diet include nausea, vomiting, constipation, dehydration, hepatitis, pancreatitis, hypoglycemia, hyperuricemia, hypomagnesemia, hyponatremia, hypercholesterolemia and hypertransaminemia24. After the introduction of antiseizure medications, the usage of the ketogenic diet to treat epilepsy has decreased25. However, recently there have been published various studies, where the ketogenic diet is applied to improve the conditions of patients with other diseases. For instance, some suggest that this diet can improve cognitive functioning in people with Alzheimer’s disease or nonmotor symptoms in patients with Parkinson’s disease24. Also, the effect of the ketogenic diet has been studied in cancer patients or people who want to lose weight25. Results show that in overweight patients with type II diabetes it can significantly reduce glycated haemoglobin, cause weight loss, and a reduction in diabetes medication25. To summarise, the ketogenic diet can be beneficial to improve the patient’s condition with various diseases, however, further evidence and research in this field are necessary.
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Figure 3: Ketogenic diet can be described as low in carbohydrates, moderate in proteins and high in fats.
Author: Guoda Radaviciute, 5th year Pharmacy student at Vilnius University.
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References [1] Adrienne R. Barnosky, Kristin K. Hoddy, Terry G. Unterman, Krista A. Varady, Intermittent fasting vs daily calorie restriction for type 2 diabetes prevention: a review of human findings, Translational Research, Volume 164, Issue 4, 2014, Pages 302-311, ISSN 1931-5244, https://doi.org/10.1016/j.trsl.2014.05.013. [2] Bergman, R.N., Kim, S.P., Catalano, K.J., Hsu, I.R., Chiu, J.D., Kabir, M., Hucking, K. and Ader, M. (2006), Why Visceral Fat is Bad: Mechanisms of the Metabolic Syndrome. Obesity, 14: 16S-19S. https://doi.org/10.1038/oby.2006.277 [3] Bahr LS, Bock M, Liebscher D, Bellmann-Strobl J, Franz L, Prüß A, Schumann D, Piper SK, Kessler CS, Steckhan N, Michalsen A, Paul F, Mähler A. Ketogenic diet and fasting diet as Nutritional Approaches in Multiple Sclerosis (NAMS): protocol of a randomized controlled study. Trials. 2020 Jan 2;21(1):3. doi: 10.1186/s13063-019-3928-9. PMID: 31898518; PMCID: PMC6941322. [4] Martin, B., Mattson, M. P., & Maudsley, S. (2006). Caloric restriction and intermittent fasting: two potential diets for successful brain aging. Ageing research reviews, 5(3), 332–353. https://doi.org/10.1016/j.arr.2006.04.002 [5] Mattson MP, Longo VD, Harvie M. Impact of intermittent fasting on health and disease processes. Ageing Res Rev. 2017 Oct; 39:46-58. doi: 10.1016/j.arr.2016.10.005. Epub 2016 Oct 31. PMID: 27810402; PMCID: PMC5411330. [6] Redman, Leanne M. et al. Metabolic Slowing and Reduced Oxidative Damage with Sustained Caloric Restriction Support the Rate of Living and Oxidative Damage Theories of Aging. Cell Metabolism, Volume 27, Issue 4, 805 815.e4 doi:https://doi.org/10.1016/j.cmet.2018.02.019 [7] Ho, K. Y., Veldhuis, J. D., Johnson, M. L., Furlanetto, R., Evans, W. S., Alberti, K. G., & Thorner, M. O., 1988. Fasting enhances growth hormone secretion and amplifies the complex rhythms of growth hormone secretion in man. The Journal of clinical investigation, 81(4), 968–975. [8] Zhu Y, Yan Y, Gius DR, Vassilopoulos A. Metabolic regulation of Sirtuins upon fasting and the implication for cancer. Curr Opin Oncol. 2013 Nov;25(6):630-6. doi: 10.1097/01.cco.0000432527.49984.a3. PMID: 24048020; PMCID: PMC5525320. [9] Preyat N, Leo O. Sirtuin deacylases: a molecular link between metabolism and immunity. J Leukoc Biol. 2013 May;93(5):669-80. doi: 10.1189/jlb.1112557. Epub 2013 Jan 16. PMID: 23325925. EPSA – European Pharmaceutical Students’ Association
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[10] Fond G, Macgregor A, Leboyer M, Michalsen A. Fasting in mood disorders: neurobiology and effectiveness. A review of the literature. Psychiatry Res. 2013 Oct 30;209(3):253-8. doi: 10.1016/j.psychres.2012.12.018. Epub 2013 Jan 15. PMID: 23332541. [11] Rozalyn M. Anderson, Richard Weindruch, Metabolic reprogramming, caloric restriction and aging, Trends in Endocrinology & Metabolism, Volume 21, Issue 3, 2010, Pages 134-141, ISSN 1043-2760, https://doi.org/10.1016/j.tem.2009.11.005. [12] Harney DJ, Hutchison AT, Hatchwell L, Humphrey SJ, James DE, Hocking S, Heilbronn LK, Larance M. Proteomic Analysis of Human Plasma during Intermittent Fasting. J Proteome Res. 2019 May 3;18(5):2228-2240. doi: 10.1021/acs.jproteome.9b00090. Epub 2019 Apr 1. PMID: 30892045; PMCID: PMC6503536. [13] Wegman, M. P., Guo, M. H., Bennion, D. M., Shankar, M. N., Chrzanowski, S. M., Goldberg, L. A., Xu, J., Williams, T. A., Lu, X., Hsu, S. I., Anton, S. D., Leeuwenburgh, C., & Brantly, M. L. (2015). Practicality of intermittent fasting in humans and its effect on oxidative stress and genes related to aging and metabolism. Rejuvenation research, 18(2), 162–172. https://doi.org/10.1089/rej.2014.1624 [14] Biesiekierski JR. What is gluten? J Gastroenterol Hepatol. 2017 Mar;32 Suppl 1:78-81. doi: 10.1111/jgh.13703. PMID: 28244676. [15] Leonard MM, Sapone A, Catassi C, Fasano A. Celiac Disease and Nonceliac Gluten Sensitivity: A Review. JAMA. 2017 Aug 15;318(7):647-656. doi: 10.1001/jama.2017.9730. PMID: 28810029. [16] Losowsky MS. A history of coeliac disease. Dig Dis. 2008;26(2):112-20. doi: 10.1159/000116768. Epub 2008 Apr 21. PMID: 18431060. [17] Parzanese, I., Qehajaj, D., Patrinicola, F., Aralica, M., Chiriva-Internati, M., Stifter, S., Elli, L., & Grizzi, F. (2017). Celiac disease: From pathophysiology to treatment. World journal of gastrointestinal pathophysiology, 8(2), 27–38. https://doi.org/10.4291/wjgp.v8.i2.27 [18] de Roest RH, Dobbs BR, Chapman BA, Batman B, O'Brien LA, Leeper JA, Hebblethwaite CR, Gearry RB. The low FODMAP diet improves gastrointestinal symptoms in patients with irritable bowel syndrome: a prospective study. Int J Clin Pract. 2013 Sep;67(9):895-903. doi: 10.1111/ijcp.12128. Epub 2013 May 23. PMID: 23701141.
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[19] Lerner BA, Green PHR, Lebwohl B. Going Against the Grains: Gluten-Free Diets in Patients Without Celiac Disease-Worthwhile or Not? Dig Dis Sci. 2019 Jul;64(7):1740-1747. doi: 10.1007/s10620-019-05663-x. PMID: 31102129. [20] Lis D, Stellingwerff T, Kitic CM, Ahuja KD, Fell J. No Effects of a Short-Term Gluten-free Diet on Performance in Nonceliac Athletes. Med Sci Sports Exerc. 2015 Dec;47(12):2563-70. doi: 10.1249/MSS.0000000000000699. PMID: 25970665. [21] Chen, X., Zhang, Z., Yang, H. et al. Consumption of ultra-processed foods and health outcomes: a systematic review of epidemiological studies. Nutr J 19, 86 (2020). https://doi.org/10.1186/s12937-020-00604-1 [22] Niland B, Cash BD. Health Benefits and Adverse Effects of a Gluten-Free Diet in Non-Celiac Disease Patients. Gastroenterol Hepatol (N Y). 2018 Feb;14(2):82-91. PMID: 29606920; PMCID: PMC5866307. [23] Keith, L. et al. (2021). Ketogenic diet as a potential intervention for lipidema. Medical hypothesis 146. [24] Wlodarek. D. (2019). Role of ketogenic diets in neurodegenerative diseases (Alzheimer’s disease and Parkinson’s disease). Nutrients 11 (1). [25] Mundi, M.S. (2021). Ketogenic diet and cancer: fad or fabulous? Journal of parenteral and enteral nutrition 45: 26 – 32. [26] Kim, Y.J. (2021). Optimal diet strategies for weight loss and weight loss maintenance. Journal of Obesity and Metabolic Syndrome 30 (1): 20 – 31.
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References for pictures: Front page image: https://unsplash.com/photos/-ftWfohtjNw by Nadine Primeau. Figure 1: Bronwen Martin, Mark P. Mattson, Stuart Maudsley, Caloric restriction and intermittent fasting: Two potential diets for successful brain aging, Ageing Research Reviews, Volume 5, Issue 3, 2006, Pages 332-353, ISSN 1568-1637, https://doi.org/10.1016/j.arr.2006.04.002. Figure 2: Article by Joseph Pizzimenti, OD, and Carlo Pelino, OD, Review of Optometry, “Hold the gluten please” Published May 15, 2013, https://www.reviewofoptometry.com/article/hold-the-gluten-please Figure 3: Kemin (2019). The Keto diet. URL: https://www.kemin.com/na/en-us/blog/human-nutrition/weighing-in-on-the-keto-diet [Accessed 2022-01-20].
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