Essential bibliography on food- and sugar-induced inflammation

This section presents an essential bibliography on food- and sugar-induced inflammation: a carefully curated collection of scientific articles that form the foundation of our work and the basis of the GEK Lab method. Particular attention is devoted to inflammation caused by sugars and to glycation processes, which play a central role in sustaining low-grade chronic inflammation. These studies represent the pillars of our research, providing solid scientific evidence to address inflammation and its long-term effects on health.

For an introduction to our methodological foundations, the following articles may also be consulted:

What if it’s all due to inflammation?

Inflammation from sugars and glycation

Food-related inflammation

To date, at least three distinct forms of food-induced inflammation have been identified, each with unique characteristics but synergistic effects.

nflammation related to an improper balance of nutrients in each meal

In 2011, the Harvard School of Public Health established simple guidelines for properly balancing nutrients within each meal. These recommendations serve as the first tool to control inflammation through the correct distribution of carbohydrates, proteins, and fiber in a single meal.

Inflammation related to an individually excessive intake of sugars

Glycemic variability and fluctuations in blood glucose levels are responsible for significant and often irreversible alterations of protein and cellular structures; hyperglycemia, for example, leads to the glycation of numerous molecules, including many proteins, whose function is closely linked to their three-dimensional structure.
As clearly defined by a multicenter study conducted in the European Union, 62% of inflammatory or allergic reactions of unknown origin are multifactorial, and glycation processes—resulting from excessive dietary intake of rapidly absorbed carbohydrates and sugars (including fructose)—are among the major contributing factors.

Inflammation related to excessive or repeated consumption of the same food or food group

Excessive or repetitive consumption of the same food, or of foods within the same food group, can stimulate the production of specific immunoglobulin G (IgG) and the release of inflammatory cytokines (such as BAFF and PAF). These cytokines are involved in numerous disorders and autoimmune diseases, including Lupus, Sjögren’s Syndrome, and Rheumatoid Arthritis, as well as in inflammatory conditions affecting the intestines, respiratory system, skin, eyes, and more.

Bibliography:

1. Healthy Eating Plate | The Nutrition Source | Harvard T.H. Chan School of Public Health.

Available at: https://www.hsph.harvard.edu/nutritionsource/healthy-eating-plate/.

2. Anto JM et al. J Allergy Clin Immunol. 2017;139:388-99. doi:10.1016/j.jaci.2016.12.940

3. Smith PK et al. J Allergy Clin Immunol. 2017;139:429-37. doi:10.1016/j.jaci.2016.05.040

4. Schmidt MI et al. Lancet Diabetes Endocrinol. 2019;7:267-77. doi:10.1016/S2213-8587(19)30058-0

5. Richter B et al. Cochrane Database Syst Rev. 2018;10:CD012661. doi:10.1002/14651858.CD012661.pub2.

6. Rodriguez-Segade S et al. Acta Diabetol. 2019;56:1023-30. doi:10.1007/s00592-019-01342-5

7. Piuri G et al. Nutrients. 2019;11:1096. doi:10.3390/nu11051096

8. Fabris M et al. Scand J Gastroenterol. 2007;42:1434-9. doi:10.1080/00365520701452225

9. Piuri G et al. Clin Transl Allergy. 2013;3:O5. doi:10.1186/2045-7022-3-S3-O5

10. Kang S et al. J Immunol. 2016;196:196-206. doi:10.4049/jimmunol.1402527

11. Cappelletti M et al. Nutr Metab. 2020;17:101. doi:10.1186/s12986-020-00528-x

Understanding the role of food-induced inflammation is essential for identifying dietary habits that help control the potential harmful effects of poor nutrition on the body.
Throughout life, every person experiences inflammatory events, which differ in both symptoms and duration. Today, inflammation can be measured easily, much like using a thermometer to measure a fever.

Knowing inflammation levels, including those related to food, is a key step in establishing and restoring proper immune balance. Measuring levels of BAFF (B-Cell Activating Factor) and PAF (Platelet Activating Factor) helps define the most appropriate dietary approach to reduce inflammation.

Bibliography:

1. Tay J et al. Pregnancy Hypertens. 2018;13:58-61. doi:10.1016/j.preghy.2018.05.001
2. Piuri G et al. Nutrients. 2020;12:479. doi:10.3390/nu12020479
3. Kim YH et al. Exp Mol Med. 2009;41:208-16. doi:10.3858/emm.2009.41.3.024
4. Paudel YN et al. Cells 2020; 9:383. doi:10.3390/cells9020383

Since 2011, the Harvard School of Public Health has proposed a framework highlighting the value of protein and emphasizing the importance of including the right amount in each meal. The “Healthy Eating Plate” encourages the use of whole grains instead of refined ones and emphasizes the proportion of different nutrients, thereby avoiding calorie counting.

Bibliography:

1. Healthy Eating Plate | The Nutrition Source | Harvard
   T.H. Chan School of Public Health. Available at:
   https://www.hsph.harvard.edu/nutritionsource/healthy-eating-plate/.

Diabetes and other sugar-related diseases are rapidly becoming “pandemic.” This underscores the importance of early diagnosis and treatment of a “pre-diabetic” condition, before metabolic alterations and insulin resistance (also reflected by elevated fasting glucose and glycated hemoglobin) become significant and difficult to manage. It is estimated that preventing diabetes by addressing potential genetic predispositions and lifestyle-related factors could add 8 to 13 years of healthy life (1).

A similar consideration applies to almost all chronic degenerative diseases. Controlling inflammation and sugar sensitivity can help gain additional years of “high-quality” life and well-being.

Bibliography:

1. Leal J et al. Eur Heart J. 2009;30:834-9. doi:10.1093/eurheartj/ehn567.
2. Anto JM et al. J Allergy Clin Immunol. 2017;139:388-99. doi:10.1016/j.jaci.2016.12.940
3. Smith PK et al. J Allergy Clin Immunol. 2017;139:429-37. doi:10.1016/j.jaci.2016.05.040
4. Piuri G et al. Nutrients. 2020;12:479. doi:10.3390/nu12020479
5. Di Martino D et al. Nutrients. 2022;14:4037. doi:10.3390/nu14194037
6. Richter B et al. Cochrane Database Syst Rev.2018;10:CD012661. doi:10.1002/14651858.CD012661.pub2.
7. Rodriguez-Segade S et al. Acta Diabetol. 2019;56:1023-30. doi:10.1007/s00592-019-01342-5
8. Paudel YN et al. Cells 2020; 9:383. doi:10.3390/cells9020383
9. Cropano C et al. Diabetes Care.2017;40:1082-9. doi:10.2337/dc17-0290.
10. Steri M et al. N Engl J Med. 2017;376:1615-26. doi:10.1056/NEJMoa1610528
11. González-Serna D et al. Sci Rep. 2018;8:8195. doi:10.1038/s41598-018-26573-4
12. Lyssenko V et al. J Clin Invest. 2007;117:2155-63. doi:10.1172/JCI30706
13. Zeggini E et al. Science. 2007;316:1336-41. doi:10.1126/science.1142364
14. Zeggini E et al. Nat Genet. 2008;40:638-45. doi:10.1038/ng.120
15. Frayling TM et al. Science. 2007;316:889-94. doi:10.1126/science.1141634
16. BasuRay S et al. Hepatology. 2017;66:1111-24. doi:10.1002/hep.29273
17. Wang J-Z et al. World J Clin Cases. 2018;6:167-75. doi:10.12998/wjcc.v6.i8.167
18. Lustig RH. Adv. Nutr. 2013;4:226-35. doi:10.3945/an.112.002998.

For a long time, ESR (erythrocyte sedimentation rate) and CRP (C-reactive protein) were the only available biomarkers for assessing inflammation.

These two biomarkers remain extremely useful in clinical practice, especially for evaluating infections or acute “high-grade” systemic inflammation; however, they often show poor correlation with symptoms and lack the specificity and sensitivity needed to identify low-grade inflammation.

Several members of the Tumor Necrosis Factor (TNF) family play an important role in both inducing and maintaining inflammatory conditions (2,3). Among these, B-Cell Activating Factor (BAFF) and Platelet Activating Factor (PAF) could be used as “thermometers” to measure the extent of systemic inflammation, including food-related inflammation.

BAFF and its gene (TNFSF13B) have been associated with immune risk and pathological disease progression, as demonstrated by a multicenter study published in the New England Journal of Medicine (14). Individuals with allergic asthma or autoimmune diseases (such as SLE, Sjögren’s syndrome, rheumatoid arthritis, systemic sclerosis, cryoglobulinemia, and myasthenia gravis) have shown elevated BAFF levels (4-6).

PAF (Platelet Activating Factor) is a phospholipid first described in the 1970s as a factor responsible for platelet aggregation (10).Over time, PAF has been shown to be an important mediator of various physiological and pathological processes, including inflammation. Scientific evidence indicates that PAF is a key mediator of food-related inflammatory and allergic responses

Bibliography:

1. Bray C et al. WMJ. 2016;115:317-21.PMID: 29094869.
2. Zelová H, Hošek J. Inflamm Res. 2013; 62:641-51. doi:10.1007/s00011-013-0633-0.
3. Sutherland APR et al. J Immunol. 2005;174:5537-44. doi: 10.4049/jimmunol.174.9.5537.
4. Moisini I et al. Clin. Exp. Immunol. 2009;158:155-63. doi: 10.1111/j.1365-2249.2009.04007.x.
5. Nishikawa, H. et al. Medicine.2016;95:e3194. doi:10.1097/md.0000000000003194.
6. Wei, F. et al. Int. Immunopharmacol.2016;31:1-8. doi:10.1016/j.intimp.2015.12.007.
7. Kim YH et al. Exp Mol Med. 2009;41:208-16. doi:10.3858/emm.2009.41.3.024
8. Fabris M et al. Scand J Gastroenterol. 2007;42:1434-9. doi:10.1080/00365520701452225
9. Lied GA et al. Aliment Pharmacol Ther. 2010;32:66-73. doi:10.1111/j.1365-2036.2010.04314.x
10. Speciani AF J Am Coll Nutr. 2015;34 S1:34-8 doi: 10.1080/07315724.2015.1080109
11. Reznichenko A, Korstanje R. Am. J. Pathol. 2015; 185;888-96 doi: 10.1016/j.ajpath.2014.11.025.
12. Finkelman FD et al. J Allergy Clin Immunol. 2007;120:506-15. doi:10.1016/j.jaci.2007.07.033
13. Piuri G et al. Clin Transl Allergy. 2013;3:O5. doi:10.1186/2045-7022-3-S3-O5
14. Steri M et al. N Engl J Med. 2017;376:1615-26. doi:10.1056/NEJMoa1610528
15. González-Serna D et al. Sci Rep. 2018;8:8195. doi:10.1038/s41598-018-26573-4
16. Mackay F, Browning J. Nat. Rev. Immunol. 2002;2:465-75. doi: 10.1038/nri844.
17. Finkelman FD et al. J Allergy Clin Immunol. 2016;137:1674-80. doi:10.1016/j.jaci.2016.02.015
18. Cianferoni A et al. J Allergy Clin Immunol. 2021;147:1123-31. doi: 10.1016/j.jaci.2021.02.012
19. Bentz S et al. Digestion. 2010;81:252-64. doi:10.1159/000264649
20. Biesiekierski JR, Iven J. Gastroenterol. J. 2015; 3:160-5 doi: 10.1177/2050640615578388.
21. Guo H et al. J. Int. Med. Res. 2012;40:204-10. doi: 10.1177/147323001204000121.
22. Uzunısmaıl H et al. Turk. J. Gastroenterol.2012; 23:19-27. doi: 10.4318/tjg.2012.0332.
23. Cappelletti M et al. Nutr Metab. 2020;17:101. doi:10.1186/s12986-020-00528-x
24. Piuri G et al. Nutrients. 2019;11:1096. doi:10.3390/nu11051096
25. Speciani A et al. Clin Transl Allergy. 2013;3:P67. doi:10.1186/2045-7022-3-S3-P67
26. Speciani FA et al. Clin Transl Allergy. 2015;5:P39. doi:10.1186/2045-7022-5-S3-P39

Most diets fail in the long term because they focus solely on calories and fixed protocols. Precision medicine can create a “tailor-made” diet that takes into account multiple aspects of an individual (such as dietary profile, inflammation, and genetics).
The best and most effective nutritional choices depend on personalized meal plans that consider individual levels of inflammation (both food- and sugar-related) and the proper composition of meals (for example, the ratio of carbohydrates to proteins).

The recommendation to restrict and avoid certain foods was the first approach to managing adverse food reactions. However, today the risks associated with food elimination are clear: long-term avoidance can lead to a loss of antigen recognition for that specific food, potentially resulting in strong immune-mediated reactions (including anaphylaxis) when the food is consumed, even accidentally and/or in small amounts.

Bibliography:

1. Larramendi CH et al. Allergy. 1992;47:490-4. doi: 10.1111/j.1398-9995.1992.tb00670.x.
2. Martelletti P et al. Headache. 1989;29;664-70. doi:10.1111/j.1526-4610.1989.hed2910664.x.
3. Cappelletti M et al. Nutr Metab. 2020;17:101. doi:10.1186/s12986-020-00528-x
4. Ligaarden SC et al. BMC Gastroenterol. 2012;12:166. doi:10.1186/1471-230X-12-166
5. Speciani, A. F. & Piuri, G. Like a pressure cooker. (Gek s.r.l. publisher, 2014).
6. Kang S et al. J Immunol. 2016;196:196-206. doi:10.4049/jimmunol.1402527

Telomeres are repeated nucleotide sequences at the ends of linear chromosomes, whose function is to protect coding sequences during DNA replication (affected by time, aging, and oxidation). Telomere shortening is a physiological process necessary for cellular replication; however, an accelerated rate can be a sign of premature aging and a potential onset of disease.

Bibliography:

1. Lustig RH. Adv. Nutr. 2013;4:226-35. doi:10.3945/an.112.002998.
2. Puterman E et al. PloS One. 2010; 5:e10837. doi:10.1371/journal.pone.0010837.
3. Jurk D et al. Nat Commun. 2014;5:4172. doi:10.1038/ncomms5172
4. Jackowska M et al. PLoS One. 2012;7:e47292. doi:10.1371/journal.pone.0047292

Edited by the GEK LAB scientific editorial team