Extracts of turmeric, the root of the Curcuma longa plant is credited with many health enhancing qualities. These are 1) reduction of pain and debilitation of osteoarthritis, 2) inhibition of cancer growth, and 3) slowing of age-related cognitive decline, to name a few. These benefits are the reported and marketed treasures of turmeric extracts. Many older adults self medicate with turmeric extracts because of these claims. However, the trouble is simply that turmeric extracts are poorly bioavailable (are not absorbed and remain in the gut) and hence the chemical characteristics of turmeric extracts prevent a meaningful biological effect.
Historically, the initial excitement claiming turmeric extracts caused a perfusion of effects (antioxidative, anti-inflammatory, anticancer) derived from assays lacking relevant controls. This published data persists and is abundantly quoted. Many clinical trials assessed the benefits of turmeric extracts, but trials are small and results preliminary and controversial.
This blog will discuss the pros and cons of turmeric extracts relevant to purported health benefits in joint pain and cognitive decline, conditions of interest to the older adult.
Turmeric Extracts: Curcumin is the Biological Component of Interest
Powdered turmeric is a popular yellow spice. It is used on its own for its distinct flavor, as a significant component of curry powder and as a yellow food coloring. Additionally, alcohol extracts of the turmeric root have been used for centuries as an Asian herbal remedy for a variety of health problems and is currently the form studied in clinical trials for many of those same conditions.
The “active” components in alcohol extracted turmeric roots are chemical entities identified as curcuminoids, chief of which is curcumin. Two other curcuminoids with slightly modified chemical structures are also present but in very small amounts. Health benefits are predominately attributed to curcumin. Over-the-counter (OTC) turmeric extracts contain 80% or more of curcumin. However, the curcumin content of turmeric extracts vary from supplier to supplier. Turmeric extracts are dietary supplements. Unlike prescription drugs, the FDA does not regulate dietary supplements for efficacy and safety. Suppliers of dietary supplements need only follow good manufacturing practices (GMP) without governmental oversight.
Curcumin: Poorly Bioavailable and Chemically Unstable
Absorption of curcumin into the body after oral intake is extremely poor. In fact, the absorption of curcumin is negligible and generally not even detectable in serum even after consumption of as much as12 grams/day. This is largely due to the chemical structure of curcumin. It is unstable in biological fluids at biological temperatures. Adding to this is its inability to cross the intestinal wall and its breakdown in the liver. Consequently, it never gets into body compartments to induce a meaningful effect.
The abysmal absorption of curcumin has generated extreme interest in the development of chemical/physical modifications to enhance absorption. In a study comparing novel formulations such as curcumin associated with fats, oils, adjuvants e.g. piperine (black pepper derivative), carbohydrates e.g. gamma cyclodextrin and micelles (nanoparticles encapsulating curcumin) only the latter two improved absorption to the extent that a metabolic product of curcumin but not curcumin, itself, was detected in the serum. With such a weak presence in serum, it is reasonable to ask how can curcumin exert biological effects?
Turmeric Extracts – Multiplicity of Health Benefits of Curcumin?
Some of the reported beneficial effects of curcumin are “anti-inflammatory, anti-HIV, antibacterial, antifungal, nematocidal (killing nematode infection), anti-parasitic, antimutagenic (blocking DNA damage), antidiabetic, antifibrinogenic (preventing blood clots), radioprotective (protecting against radiation), wound healing, lipid lowering, antispasmodic (relieving muscle cramps), antioxidant, immunomodulating (assisting the immune system), anticarcinogenic” (Nelson et al., 2017).
However, a critical review of the in vitro assays that support this diversity of effects indicates that the chemical instability of curcumin artificially interferes with assay results such that the results are not biological but simply artefactual (not real). In fact, curcumin is a pan-assay interference compound. This means that it creates havoc in assays. It does this is by disruption of cell membranes, inappropriately binding to proteins, forming aggregates (bunching up of proteins) and/or altering the fluorescence detection readout, as some examples. These activities are unrelated to the biological objective of the assay. Very few studies have controlled for these unwanted and interfering effects. Thus, exactly what biological effects curcumin may possess is not clear.
Turmeric Extracts – Clinical Trial Results
Many small studies (20-200 enrolled individuals) assessed curcumin for the treatment of osteoarthritis, cancer, and cognitive decline. Since the results of a single small study carries little weight, researchers use a statistical approach termed a meta-analysis. This allows the data from similar clinical trials to be added together and statistically analyzed, a technique that strengthens the final conclusion. However, inclusion of a clinical trial in a meta-analysis must meet strict criteria e.g. randomization, clear end points, accurate verifiable measurements, specified duration and many more. Out of hundreds of trials, usually 7-20 or so make the cut into a meta-analysis.
Likely Use of Turmeric Extracts by Older Individuals
Most older adults have some degree of joint inflammation known as osteoarthritis. The joint inflammation produces pain, stiffness, and swelling and limits mobility. An effective therapy is the use of the nonsteroidal antiinflammatory OTC drugs e.g. naproxen and ibuprofen. However, some also seek herbal remedies such as turmeric extracts (curcumin) that are touted as highly effective treatments for osteoarthritis.
1. Do turmeric extracts reduced debilitating symptoms of osteoarthritis?
A meta-analysis of curcumin use in knee-osteoarthritis identified 8 clinical trials that met their criteria. Two subjective assessment scores, accepted as both valid and reliable defined the severity of pain, stiffness and swelling. The USA completed one trial and Asia and Italy the others. Turmeric extract (curcumin ~1000 mg/day) used for 4 weeks to 4 months in 45-100 subjects reduced symptoms of knee osteoarthritis. Adverse effects were no different than placebo or OTC antiinflammatory medications. However, since the total number of patients was small (even when all studies were combined) and there was some quality issues with the data, these results are not considered definitive. Furthermore, some of the trials used proprietary preparations of curcumin, not available OTC.
Three more recent meta-analyses (2021-2022) found that turmeric extracts ameliorated symptoms of knee osteoarthritis compared to placebo and comparable to OTC anti-inflammatory drugs. These analyses each included a greater number of clinical trials (15-16), hence combining a greater number of subjects (up to 1800 subjects total). Most trials used proprietary formulations of curcumin. India, China, Iran and Thailand hosted the majority of studies. However, the authors of all meta-analyses projected caution in interpretation of results due to poor quality of the data and presence of moderate bias.
Another likely use of Turmeric Extracts.
Older adults are anxious that their mental acuity may decline with age. Hence, remedies that prevent or at least slow cognitive decline are of keen interest. Turmeric extracts are marketed as beneficial in this respect.
2. Do turmeric extracts reduce cognitive decline?
Results of clinical trial thus far are not convincing that consumption of turmeric extracts improves thinking ability. There are no meta-analyses. Eight clinical trials (2008 -2020) assessed the effect of turmeric extracts (curcumin) consumption on cognitive function in older adults. Studies were small (27-152 subjects), lasting 4 weeks to 1 year, and most used proprietary preparations of curcumin or precisely defined the amount of extracted curcumin in each capsule.
Subjects completed a battery of mental tests that examine a range of cognitive domains. Short term memory improved in 2 of the 8 trials. Other cognitive domains did not improve. In one trial, short term memory improved at 6 hours post dosing and at 4 weeks of daily dosing in prediabetic subjects. In another study, 16 weeks of daily dosing in overweight/obese males (not females) increased short term memory. Immediate recall tests (e.g. recalling a list of 15 words after specified time periods or performing serial subtraction of, for example, 7 from 100) served to assess short term memory. How results of these memory test translate into enhanced daily thinking in general is unclear.
Are Turmeric Extracts Safe?
The FDA considers the turmeric spice a generally recognized as safe (GRAS) product (FDA notice 460) when added to food (for flavor, flavor enhancement) at 20 mg/serving. Companies marketing curcuminoids may receive a GRAS label if they submit extensive data to the FDA on chemistry, specifications, and toxicology in animals and humans. One example is GRAS notice 822 from Laurus Labs. Laurus Lab’s curcumin received the GRAS label when used at 0.5-100 mg/100 g of food. However, most companies do not have FDA GRAS approval for their OTC curcumin product.
In human clinical trials, use of gram doses of turmeric extracts appear safe. Results of clinical trials report adverse effects comparable to placebo or antiinflammatory drugs (e.g. ibuprofen). Adverse effects generally include various types of gastrointestinal (GI) upsets. This is not surprising since turmeric extracts are poorly absorbed (even preps modified to improve absorption) and thus these products basically remain in the GI tract until eliminated.
How to explain the small biological effects of turmeric extracts?
The active component of turmeric extracts, the curcuminoids, are incredibly chemically unstable in and out of the human body. How then to explain the small effects reported in clinical trials. This is possibly a result of the small number of participants in these trials that generate considerable bias and hence false results. Alternatively, it has been proposed that the persistence of the curcuminoids in the GI tract allows interaction with the thousands of resident bacteria. These bacteria produce mediators to account for the anti-inflammatory effects in osteoarthritis and the slight immediate recall benefit.
This is an interesting concept but given the extensive number and diversity of GI bacteria, and the variation from one individual to another, this remains a challenging hypothesis to study and prove. For the time being, it is reasonably better to engage in a serious exercise program (insight 2) (insight 3) (insight 4) and participate in activities that enhance positive neuroplasticity of the brain (insight 6) to ameliorate symptoms of osteoarthritis and cognitive decline.
Conclusions
Review of the biology of turmeric extracts (curcumin) shows evidence of it poor bioavailability/chemical instability and inconclusive clinical trial results relevant to osteoarthritis and cognitive decline. Clearly, it is premature to consider this herbal remedy as of value in self-medication for joint pain and memory complaints. A large randomized clinical trial (several thousand subjects) using several doses over a period of months with turmeric extract readily available OTC would provide a definite answer.
This is one of several blogs that will review some of the OTC health products. Readers interested in a wider range of OTC drugs and dietary supplements, might check out the book: Drug Use in the Older Adult: Guide to Nurses, Other Practicing Clinicians and the Interested Older Individual authored by myself and Dr. Patricia Brown-O’Hara, expected out this spring. One full chapter discusses use of OTC products (drugs and dietary supplements). Ask your local librarian to purchase it as a necessary reference.
Selected References (http//pubmed) Additional references on request
Daily JW, Yang M, Park S. Efficacy of Turmeric Extracts and Curcumin for Alleviating the Symptoms of Joint Arthritis: A Systematic Review and Meta-Analysis of Randomized Clinical Trials J Med Food 19 (8) 2016, 717–729DOI: 10.1089/jmf.2016.3705.
Nelson KM,Dahlin JL, Bisson J, Graham J, Pauli GF, Walters MA. The Essential Medicinal Chemistry of Curcumin Miniperspective. J. Med. Chem. 2017, 60, 1620−1637 DOI: 10.1021/acs.jmedchem.6b00975.
Prasad S, Gupta SC, Tyagi AK, Aggarwal BB: Curcumin, a component of golden spice: From bedside to bench and back. Biotechnol Adv 2014;32:1053–1064.
Rainey-Smith SR, Brown BM, Sohrabi HR, Shah T, Goozee KG, Gupta VB, Martins RN. Curcumin and cognition: a randomised, placebo-controlled, double-blind study of community-dwelling older adults. Br J Nutr. 2016 Jun;115(12):2106-13. doi: 10.1017/S0007114516001203.
Turmeric: the Spice