Inflammation is a term used to describe a protective process that is elicited intermittently by the immune system in response to external substances such as pathogens, irritants and chemicals and to assist wound healing. When this critical function is dysregulated and prolonged it can become problematic and contribute to several health conditions such as diabetes and heart disease. There are many changes we can introduce into our lifestyle to minimise inflammation and its negative effects, this article will take a closer look at lemon compounds and how these help to reduce and manage inflammation.
What is inflammation?
Inflammation is a crucial physiological process which occurs when the immune system responds to bodily injury and exposure to substances which have originated outside of the body. It is responsible for the removal of harmful external stimuli and initiating healing in damaged tissue. 2000 years ago Roman physician Aulus Cornelius Celsus identified that inflammation was characterised by swelling, heat, redness and loss of function in affected organs and limbs.1 When we experience a wound such as a cut we can see evidence of this, there is usually a visible colour change such as redness or darkening of the skin and it will be warm to the touch.
When this process becomes dysregulated and sustained it is referred to as chronic inflammation so while intermittent inflammation is a healthy beneficial immune response, chronic inflammation produces negative side effects. Medical research has revealed over recent years that chronic inflammation is acutely linked to several diseases including diabetes mellitus, cancer, cardiovascular disease, and chronic kidney disease. Collectively these diseases can be referred to as chronic inflammatory diseases and are leading causes of global mortality and disability.2
Causes of chronic inflammation
The immune system has two main defence strategies: innate and adaptive, the former is non-specific while the latter is a tailored immune response. With respect to chronic inflammation, we will focus on the innate immune system which is activated very quickly once exogenous substances are detected in the body and can begin to work between minutes and hours of exposure.3 Pattern recognition receptors (PRRs) are proteins expressed primarily by innate immune cells such as dendritic cells, macrophages and neutrophils. PRRs are sensitive to detecting two key groups of molecules; pathogen-associated molecular patterns otherwise known as PAMPs and damage-associated molecular patterns or DAMPs. PAMPs can initiate an acute immune response whereas DAMPs, which are released from the body’s cells and tissues, bind to PRRs.4 This stimulates the innate immune system, activating small signalling proteins known as cytokines notably IFN-γ and TNF-α, which then attract macrophages, an important white blood cell which can also inflict cell and tissue damage resulting in long-lasting chronic inflammation.5 Oxidative stress also ensues, producing free radicals and causing DNA and tissue damage, it is highly implicated in diseases including: Alzheimer’s, diabetes, cardiovascular conditions and cancer.
Factors contributing to chronic inflammation
There are several factors which can contribute to persistent low-grade levels of inflammation:
- Poor diet, particularly high consumption of red meats
- Lack of exercise and physical movement
- Alcohol
- Obesity
- Stress
- Smoking
- Age
- Sleep deprivation
Overview of the lemon (Citrus lemon)
Lemons (Citrus lemon) are instantly recognisable from their vibrant yellow skin and signature ellipsoid shape. The lemon belongs to the Rutaceae family of flowering plants which are native to Asia. Thought to have first grown in South Asia, particularly in the Assam region of North Eastern India and Myanmar. The earliest literary reference made to citrus fruit was approximately 800 AD featured in Sanskrit literature.6 The lemon was later introduced to Southern Italy and the Mediterranean, today its distribution stretches as far as Mexico and South America.
Lemons have been used for thousands of years to aid digestion, weight loss, and prevent scurvy and are reputed to give a beautiful glow to the skin among a host of other benefits. It can be consumed in many different ways; fresh fruit, candied, pickled in brine, zest can be added to savoury dishes and desserts, the skin can be dehydrated and ground into a powder to be used as a supplement or flavouring and drank in the form of a tea.
Other health benefits of lemon include:
- Prevent against kidney stones
- Aid iron absorption – protecting against anaemia
- Anti-cancer properties
Although brimming full of positive health benefits, guidelines recommend no more than 2-3 lemons a day as high levels of citric acid can damage tooth enamel and lead to an upset stomach.
Lemons aid inflammation
In traditional holistic medicines, the lemon is often featured due to the high number of bioactive compounds it contains. Phytochemicals are chemical substances produced by plants and are known to provide a wealth of benefits when incorporated into the diet. Inhibition of cancer cell proliferation, reduction of inflammation and restoring damaged DNA have all been attributed to phytochemicals. Some examples of phytochemicals include polyphenols, limonoids and flavonoids.7
Flavonoids
Flavonoids are organically synthesised polyphenols, found in plants, flowers, fruits, vegetables, spices and roots. Flavonoids can reduce inflammation by inhibiting inflammatory mediators such as transcription factors and enzymes.8
In neurodegenerative disorders flavonoids have been investigated for their neuroprotective properties, they reduce the expression of pro-inflammatory cytokines which can attack the nervous tissue of the brain ultimately causing neuronal death and contributing to multiple sclerosis, Parkinson’s and Alzheimer’s disease.9 Research has revealed that flavonoids can also increase levels of anti-inflammatory cytokines such as IL-10, which is valuable for controlling the immune response, this is evident in people who are deficient in IL-10 and are more predisposed to developing inflammatory bowel disease.10,11
Citric acid
Citric acid is a naturally occurring weak acid most abundant in citrus fruits and present in tomatoes and certain berries in reduced quantities. This acid gives lemons and limes their characteristic sour taste but is also responsible for a wealth of benefits. Experimental data has revealed that citric acid may facilitate a decrease in oxidative stress in the brain. Lipopolysaccharides (LPS) constitute a large portion of the cell walls of certain bacteria and are used experimentally to induce inflammation. When subjected to LPS, malondialdehyde (MDA), a marker of oxidative stress and brain trauma, was significantly reduced when citric acid was also featured compared with LPS alone.12
Citric acid can reduce levels of nitric oxide, a product of oxidative stress which is highly implicated in inflammation and neuronal cell death due to its interactions with other free radicals which form highly cytotoxic substances.
Limonene
Limonene belongs to a group of chemicals known as terpenes, naturally produced in a wide range of plants and flowers. Aromatic in nature, terpenes represent a large portion of the components that make up essential oils and provide them with easily recognisable odours. In lemons and other citrus fruits, limonene is present in high quantities in the essential oils of its peels. Limonene is used for its medicinal properties; it can act as a sedative, is anti-inflammatory, and antitoxic and also exhibits antioxidant properties as it can inhibit NO production.13 Limonene can reduce levels of the pro-inflammatory cytokine TNF-α and also the prostaglandin E2 (PGE2). Prostaglandins are lipids which mimic hormone action, PGE2 has a key role in inducing labour but is also significant in inflammation and its inhibition by limonene further shows how lemons can contribute to reducing inflammation.
Summary
Inflammation is an essential process in the human body helping to protect us from damage from pathogens, and irritants and accelerate wound healing. On the other hand, when this process is in disequilibrium and persists for a prolonged period, it can reap chaos in physiological processes, damaging tissues and causing harm to the body. There are several factors which can increase the chances of a person developing chronic inflammation including age, diet, sleep deprivation and smoking habits. However, implementing a healthy lifestyle can help to minimise the risk of any chronic inflammation experienced. A well-balanced diet is a vital way to aid the vitality and longevity of the body and mind and eating a rich variety of food is the key to doing so. Lemons have been used for thousands of years in holistic medicine for hydration, digestion, kidney stones, weight loss and decreasing inflammation. Research now provides data to support these claims and shows how different components of lemon reduce oxidative stress and the production of inflammation-inducing substances. Adding them to your diet can be easily done and will add a delicious flavour to dishes and beverages. However, it is important to avoid exceeding recommended consumption and consult your medical professional if you have a pre-existing health condition or are on medication.
References
- Stankov SV. Definition of Inflammation, Causes of Inflammation and Possible Anti-inflammatory Strategies. Open Inflammation Journal. 2012;5:1-9.
- Furman D, Campisi J, Verdin E, Carrera-Bastos P, Targ S, Franceschi C, et al. Chronic inflammation in the etiology of disease across the lifespan. Nat Med [Internet]. 2019 Dec [cited 2023 Nov 12];25(12):1822–32. Available from: https://www.nature.com/articles/s41591-019-0675-0
- Aristizábal B, González Á. Innate immune system. In: Autoimmunity: From Bench to Bedside [Internet] [Internet]. El Rosario University Press; 2013 [cited 2023 Nov 13]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK459455/
- Suzuki K. Chronic inflammation as an immunological abnormality and effectiveness of exercise. Biomolecules [Internet]. 2019 Jun 7 [cited 2023 Nov 13];9(6):223. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6628010/
- Feghali CA, Wright TM. Cytokines in acute and chronic inflammation. Front Biosci. 1997 Jan 1;2:d12-26.
- Scora RW. On the history and origin of citrus. Bulletin of the Torrey Botanical Club [Internet]. 1975 [cited 2023 Nov 13];102(6):369–75. Available from: https://www.jstor.org/stable/2484763
- Thakur M, Singh K, Khedkar R. 11 - Phytochemicals: Extraction process, safety assessment, toxicological evaluations, and regulatory issues. In: Prakash B, editor. Functional and Preservative Properties of Phytochemicals [Internet]. Academic Press; 2020 [cited 2023 Nov 15]. p. 341–61. Available from: https://www.sciencedirect.com/science/article/pii/B9780128185933000117
- Maleki SJ, Crespo JF, Cabanillas B. Anti-inflammatory effects of flavonoids. Food Chemistry [Internet]. 2019 Nov 30 [cited 2023 Nov 15];299:125124. Available from: https://www.sciencedirect.com/science/article/pii/S0308814619312300
- Spagnuolo C, Moccia S, Russo GL. Anti-inflammatory effects of flavonoids in neurodegenerative disorders. European Journal of Medicinal Chemistry [Internet]. 2018 Jun 10 [cited 2023 Nov 15];153:105–15. Available from: https://www.sciencedirect.com/science/article/pii/S0223523417306839
- Serafini M, Peluso I, Raguzzini A. Flavonoids as anti-inflammatory agents. Proceedings of the Nutrition Society [Internet]. 2010 Aug [cited 2023 Nov 15];69(3):273–8. Available from: https://www.cambridge.org/core/journals/proceedings-of-the-nutrition-society/article/flavonoids-as-antiinflammatory-agents/22B54898AA99E73BE86DC4E589E6B1E4
- Sharifinejad N, Zaki-Dizaji M, Sepahvandi R, Fayyaz F, dos Santos Vilela MM, ElGhazali G, et al. The clinical, molecular, and therapeutic features of patients with IL10/IL10R deficiency: a systematic review. Clin Exp Immunol [Internet]. 2022 Apr 27 [cited 2023 Nov 15];208(3):281–91. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9226142/
- Abdel-Salam OME, Youness ER, Mohammed NA, Morsy SMY, Omara EA, Sleem AA. Citric acid effects on brain and liver oxidative stress in lipopolysaccharide-treated mice. J Med Food. 2014 May;17(5):588–98.
- Kummer R, Fachini-Queiroz FC, Estevão-Silva CF, Grespan R, Silva EL, Bersani-Amado CA, et al. Evaluation of anti-inflammatory activity of citrus latifolia tanaka essential oil and limonene in experimental mouse models. Evidence-Based Complementary and Alternative Medicine [Internet]. 2013 May 15 [cited 2023 Nov 16];2013:e859083. Available from: https://www.hindawi.com/journals/ecam/2013/859083/