This natural polyphenol is universally known as the “wonder drug of life” [1] and has a long history of medicinal applications; 5,000 (Ayurveda) and 2,000 (Atharveda) years, respectively[2]. Throughout ancient times in the Far East, turmeric was used to treat inflammatory conditions of various organs, for liver and digestive tract problems, and for wound healing. In the 1970s, the first research on the yellow polyphenolic pigment from the Curcuma longa L. (turmeric) rhizome known as curcumin and its possible health benefits was carried out. In these and in later studies it was shown that curcumin has multiple therapeutic potentialities[3].
Mechanisms of Action
When consumed in an appropriate, bio-available form it has been shown in various preclinical and clinical trials to possess numerous biological attributes including anti-inflammatory, anti-oxidant and anti-cancer properties[4].
Some of the most effective mechanistic signalling pathways that are impacted by the consumption of curcumin include nuclear factor kappa B (NF-KB), reactive oxygen species (ROS), Wingless/Integrated (Wnt), Janus kinase-signal transducer and activator of mitogen-activated protein kinase (MAPK) and transcription (JAK/STAT).
Additionally, the somewhat benignly named P38 pathway which belongs to the MAPKs and is known as a stress-activated MAPK involved in diverse biological responses is also beneficially impacted[5]. P38 plays an important role in inflammation, cell differentiation, proliferation, motility and cell survival in response to DNA damage. This biological cascade can serve as a therapeutic target in many disorders. Indeed, extensive evidence confirms that curcumin impacts the P38 MAPK signalling pathway, through which it exerts beneficial anti-inflammatory, neuroprotective, and apoptotic effects. Hence, curcumin can positively affect inflammatory disorders and cancers, as well as increase glucose uptake in cells[6].
Studies have also strongly indicated that curcumin can be considered as safe to ingest, exhibits no major toxicity, and only protects normal cells and organs at least in part by up-regulating the nuclear factor erythroid-derived-2 related factor 2 (Nrf2)-induced antioxidant gene products[7].
Suggested use in Functional Dyspepsia
A September 2023 BMJ study was published on patients with functional dyspepsia: a chronic condition of recurring symptoms of an upset stomach that have no obvious cause and is also called “non-ulcer” stomach pain which is mostly associated with anxiety and depression[8]. This is known to affect approximately 7% of individuals in the community. The British Society of Gastroenterology (BSG) has extensive guidelines on its management, recognising its ubiquity in clinical practice.
This paper compared the use of curcumin versus omeprazole (one of the BSG recommendations) a commonly utilised proton-pump inhibitor used for treating peptic ulcer disease[9].
The scientists compared three groups: curcumin alone, curcumin plus omeprazole and omeprazole alone, but it is important to note that no placebo group was included.
It should also be noted that omeprazole is not typically the single-use drug of choice for functional dyspepsia. Conventional pharmaceutical applications would see omeprazole along with antidepressants, anxiolytics, and prokinetics.
However, that aside, the outcomes of the use of curcumin Vs omeprazole were equivocal, in effect they were equally efficacious, and the related risks of nutrient depletion, headaches, and nausea associated with omeprazole were excluded. It is also worth recognising that long term effects of omeprazole medication may also include osteoporotic changes, C diff infections and stomach cancer.
Dosing of curcumin for 28 days was 4 x 250mg, but this may be adjusted according to need as the relative bioavailability of curcumin does differ between brands. Note that the co-administration of mastic gum at 350mg three times a day for functional dyspepsia is not contraindicated and may offer a synergistic effect that has faster and longer benefit[10].
Curcumin as an anti-aging compound
Whilst there are numerous propositions for anti-aging mechanisms, converting these to clinically and personally recognisable effects can be difficult, and in many cases very expensive.
The anti-aging scientific community focuses on single and combination molecules to impede the loss of age-related elements or to enhance the removal of damaged components. In part the attraction for this research is embedded in the understanding that delaying aging is more effective and less expensive than treating specific age-related disorders, and therefore prevention is always an attractive proposition. Compounds that may postpone the onset of age-related symptoms, particularly natural compounds included in the average diet, are being thoroughly researched and curcumin is one among them[11]. It alleviates age-related symptoms, increases the lifetime of model organisms, and delays the course of age-related disorders in which cellular senescence is directly implicated.
The implications are, that ingestion of curcuminoids contributes to the many pathways associated with aging process inhibition, one in particular that is the subject of various studies is that of autophagy, the clearing of age-damaged cells[12]. Whilst this data and claimed benefits is embedded in animal models, human studies are in progress. Curcumin is known to regulate the level and activity of AMPK and, as shown in numerous studies, is able to inhibit mTOR level/activity, which suggests that it can also beneficially affect autophagy[13].
Autophagy (from the Greek words auto, meaning ‘self’, and phagein, meaning ‘to eat’) is a highly conserved pathway that degrades cellular components, such as defective organelles and aggregates of misfolded protein, through lysosomes. Autophagy is recognised as a highly selective cellular clearance pathway that is associated with the maintenance of cellular and tissue homeostasis[14]. Its role in aging, and age reversal through the ingestion of safe compounds is attracting much research, but its precise role as an antiaging mechanism requires further research, especially in regard to pharmaceuticals designed to target this process[15].
Summary
Over the past half-century, a high number of clinical trials have been accomplished to address curcumin’s efficacy, safety, and pharmacokinetics. Curcumin has been administered in several formulations, such as capsules, tablets, powder nanoparticles, liposomal encapsulation, and emulsions, with dose-escalating studies revealing that curcumin is safe at doses as high as 12 g/day for 3 months.
Including curcumin supplementation as a stand-alone or a combination therapeutic is attracting significant cross-over interest from the nutraceutical and pharmaceutical industry. It has significant operational application and carries only a very modest risk3. As a strategic compound in the management of intersecting pathways associated with non-communicable diseases and immune mediated inflammation it deserves clinical consideration.
References
[1] Gera M., Sharma N., Ghosh M., Huynh D. L., Lee S. J., Min T., et al. (2017). Nanoformulations of curcumin: an emerging paradigm for improved remedial application. Oncotarget 8, 66680–66698
[2] Akarchariya N., Sirilun S., Julsrigival J., Chansakaowa S. (2017). Chemical profiling and antimicrobial activity of essential oil from Curcuma aeruginosa Roxb., Curcuma glans K. Larsen & J. Mood and Curcuma cf. xanthorrhiza Roxb. collected in Thailand. Asian Pacific J. Trop. Biomed. 7, 881–885
[3] harifi-Rad J, Rayess YE, Rizk AA, Sadaka C, Zgheib R, Zam W, Sestito S, Rapposelli S, Neffe-Skocińska K, Zielińska D, Salehi B, Setzer WN, Dosoky NS, Taheri Y, El Beyrouthy M, Martorell M, Ostrander EA, Suleria HAR, Cho WC, Maroyi A, Martins N. Turmeric and Its Major Compound Curcumin on Health: Bioactive Effects and Safety Profiles for Food, Pharmaceutical, Biotechnological and Medicinal Applications. Front Pharmacol. 2020 Sep 15;11:01021
[4] Shamsnia HS, Roustaei M, Ahmadvand D, Butler AE, Amirlou D, Soltani S, Momtaz S, Jamialahmadi T, Abdolghaffari AH, Sahebkar A. Impact of curcumin on p38 MAPK: therapeutic implications. Inflammopharmacology. 2023 Jul 27
[5] Canovas, B., Nebreda, A.R. Diversity and versatility of p38 kinase signalling in health and disease. Nat Rev Mol Cell Biol 22, 346–366 (2021)
[6] Camacho-Barquero L, Villegas I, Sánchez-Calvo JM, Talero E, Sánchez-Fidalgo S, Motilva V, Alarcón de la Lastra C. Curcumin, a Curcuma longa constituent, acts on MAPK p38 pathway modulating COX-2 and iNOS expression in chronic experimental colitis. Int Immunopharmacol. 2007 Mar;7(3):333-42
[7] Rajabi S, Darroudi M, Naseri K, Farkhondeh T, Samarghandian S. Protective effects of curcumin and its analogues via the Nrf2 pathway in metabolic syndrome. Curr Med Chem. 2023 May 10
[8] Kongkam P, Khongkha W, Lopimpisuth C, et al Curcumin and proton pump inhibitors for functional dyspepsia: a randomised, double blind controlled trial BMJ Evidence-Based Medicine Published Online First: 11 September 2023
[9] Talley NJ, Lauritsen K The potential role of acid suppression in functional dyspepsia: the BOND, OPERA, PILOT, and ENCORE studies
Gut 2002;50:iv36-iv4
[10] Dabos KJ, Sfika E, Vlatta LJ, Frantzi D, Amygdalos GI, Giannikopoulos G. Is Chios mastic gum effective in the treatment of functional dyspepsia? A prospective randomised double-blind placebo controlled trial. J Ethnopharmacol. 2010 Feb 3;127(2):205-9
[11] Zia A, Farkhondeh T, Pourbagher-Shahri AM, Samarghandian S. The role of curcumin in aging and senescence: Molecular mechanisms. Biomed Pharmacother. 2021 Feb;134:111119
[12] Bielak-Zmijewska A, Grabowska W, Ciolko A, Bojko A, Mosieniak G, Bijoch Ł, Sikora E. The Role of Curcumin in the Modulation of Ageing. Int J Mol Sci. 2019 Mar 12;20(5):1239
[13] Sikora E., Bielak-Zmijewska A., Mosieniak G., Piwocka K. The Promise of Slow Down Ageing May Come from Curcumin. Curr. Pharm. Des. 2010;16:884–892
[14] Kirkin, V. History of the selective autophagy research: how did it begin and where does it stand today? J. Mol. Biol. 432, 3–27 (2020)
[15] Aman, Y., Schmauck-Medina, T., Hansen, M. et al. Autophagy in healthy aging and disease. Nat Aging 1, 634–650 (2021)