Turmeric – are patented extracts with greater bioavailability more effective or needed?

Turmeric – are patented extracts with greater bioavailability more effective or needed? - Tim Radak, DrPH, RDN

By Tim Radak, DrPH, RDN

In addition to the already numerous nutrition and health supplements in grocery, health food, and vitamin store aisles, additional space occupies the shelves for high potency versions of vitamins, minerals, antioxidants, and many other supplements. Some supplements are manufactured for increased bioavailability for consumers to select. More recently, products like spices  are being advertising with increased bioavailability. One such example is Turmeric, which has now reached  “super food ” status and is one of the most popular nutraceutical spice supplements sold. In 2015 alone,  Turmeric sales exceeded $50 million dollars and was the stand out ingredient for 2015 (Danniels, 2016) and is among the ten ingredients sold in dietary supplements (Halegoua-DeMarzio, 2023). The main phytochemical, Curcumin, though discovered over 100 years ago,  has now been isolated and put into supplement form and is one of the most extensively studied naturally‑derived therapeutic products of late (Perrone 2015). This extract is sold by itself, or with added Turmeric powder. The FDA has not granted any status for therapeutic benefit for  Turmeric or Curcumin (Nelson, 2017). Companies who have manufactured and patented these new products have assumed that more health benefits can be derived if the active component in Turmeric, that being Curcumin, could be made more bio-available, but available research does not support this.

Bioavailability of Turmeric

Turmeric and its most investigated and active ingredient, Curcumin, which provides Turmeric with its yellow color, does indeed has low bioavailability, as does other herbs and spices. However, because of its low molecular weight,  is able to be absorbed and cross the blood/brain barrier (Noorafshan 2013). But whether the existing level of bioavailability can or should be modified for increased benefits remains to be seen.

Effectiveness of natural Turmeric and Curcumin

Whatever the level of bioavailability nature has intended, there is usually a good reason behind it and it may not be fruitful to magnify what occurs naturally. In the case of Turmeric, as it is, or when taken in powder or root form,  or extracted Curcumin, has over 30 years of research investigation (Prasad, 2014) and has demonstrated significant anti-oxidant, anti-inflammatory, anti-microbial properties. It is considered a promising chemopreventive (Greger, 2015) with the ability to affect epigenetic events including gene expression relating to cancer cell progression and death (Teiten, 2013).  However, it should be noted that  the vast majority of studies have been conducted in animals or in vitro with unknown clinical relevance (Gibson-Moore, 2017). Some researchers suggest that the positive results observed in the laboratory are because these compounds are relatively stable in that setting but that due to its structure can be unstable from a biological standpoint when used in trials (Nelson, 2017).  The human studies available suggest  some positive but also mixed results for improvement in  patients with a variety of disease states (Gupta, 2012; Percival, 2012; Burgos-Morón, 2010; Fu, 2010; Nelson 2017; Ryan, 2013; Vasudev, 2016; Usharani, 2008; Lopresti, 2017) but overall clinical trials have not produced sufficient evidence of efficacy as has yet to be approved as a therapeutic agent ((Halegoua-DeMarzio, 2023). In the case of diseases such as Arthritis, the positive benefits are contrasted by methodological quality and sample sizes, with a need for studies with greater rigor (Daily, 2016). For Curcuminoids (one of which is Curcumin) one of its biggest claims as an anti-inflammatory, has not been supported in humans for reducing inflammation according to National Center for Complementary and Alternative Medicine (NCCAM – Turmeric).  Many studies that research Curcumin for its effect on health and disease already concentrate Curcumin to that of 100’s of times more than would occur naturally in Turmeric and it is debated whether greater concentrations of Turmeric should be considered for human usage (Nelson, 2017). Turmeric supplements, rather than Turmeric used as a spice, though a very small number of overall cases,  have also been associated with increasing risk for liver injury, several of which required hospitalization, as well as  a case of kidney failure after daily use for two years (Donelli, 2020; Halegoua-DeMarzio, 2023; Washington, 2024).

Need to go beyond Turmeric and extracts of Curcumin?

The body metabolizes and eliminates Turmeric from the body fairly rapidly,  as it does for powerful or potent substances, and is mainly metabolized in the intestine and liver, and minimal concentrations are achieved in plasma or tissues after ingestion (Burgos-Morón, 2010). And likely for a good reason, so extending the half-life of its phytochemical Curcumin for nutritional  benefit may leave the door open for possible consequences.  Some  research suggests that isolating a product into its individual components  (reductionism) has not proven very successful, given several major chronic disease rates continue to rise unabated (Fardet, 2014).

As we continue to understand the biological effects of spices, we are adding explanations for the role they play in human health; and once ingested, we are seeing complex reactions taking place. For example, the mechanisms of action for Curcumin includes transcription factors (such as nuclear factor-κB), growth factors (such as vascular endothelial cell growth factor), inflammatory cytokines (such as tumor necrosis factor, interleukin 1 and interleukin 6), protein kinases (such as mammalian target of rapamycin, mitogen-activated protein kinases, and Akt) and other enzymes (such as cyclooxygenase 2 and 5 lipoxygenase), and helps explain why Turmeric has been so actively researched (Zhou, 2011).

 This may raise questions as to what processes become affected or modified if mega doses of a highly bioavailable specific phytochemical are isolated and put into the form of a supplement. In the case of Turmeric or Curcumin, high doses are not believed to lead to toxicity (these are studies without a modified enhanced bioavailable Curcumin), however some studies have shown significant  side effects with high doses  and have raised concern over the need for longer term studies  (Gupta, 2013; Nelson, 2017 ) and in some testing conditions, toxicity was noted (Burgos-Moron, 2010).  High doses of Curcumin could affect or inhibit the livers natural detoxification processes  (Nelson 2017), alter iron metabolism which could be a concern for iron deficiency in some patients (Shen, 2016), and some research suggested that high doses in vitro affected sperm motility to the degree that Curcumin is being considered for possible usage as a natural contraceptive (Naz, 2011). Science does not always reveal its cause and effect promptly, and it is unknown what high doses of an isolated phytochemical may elicit over prolonged periods of time. Moreover, researchers also caution that we do not know of possible synergistic affects of Turmeric with drugs or other chemicals as impact or safety with current medication usage is typically not reported in studies (Trubilla, 2017) and could also interfere or contraindicate pharmaceutical drugs (Nelson, 2017). One review suggested Turmeric could be implicated with increased bleeding times when taken with  anti-coagulant anti-platelet medicines (Tsai, 2013) and others have noted Curcumin is not recommened for those with gallstones, obstructive jaundice or acute biliary colic (Mishra, 2008) or at those at risk for kidney stones due to the high oxalate content of turmeric Curcumin (Washington, 2024).

Research using patented increased bioavailability Curcumin

The available studies that have used these more bioavailable and patented forms of Curcumin have not compared it to regular Turmeric or Curcumin.  Why is this important?

To evaluate the increased effectiveness of a particular product and answer the question of any additionally derived health benefit requires correct study methodology. To do this would require comparing standard Curcumin in Turmeric to the more bioavailable patented version to see if there was any net additional benefit, and in studies that were reviewed which tested a increased bioavailable form called Longvida® Optimized Curcumin, none did this (Hazarey, 2015; Cox, 2015; McFarlin, 2016; Belcaro, 2010²; Belcaro , 2014; Allegri, 2010; Appendino, 2011; Ledda, 2012; Santos-Parker, 2017). Without a comparison of what it is claiming to be better than, we really do not know if there is any increased efficacy or benefit, and furthermore may be counterproductive for consumers if they believe one product is better than another as they strive to improve their health.  

Additionally, some research suggests that with respect to Turmeric and Curcumin, other phytochemicals or bioactive compounds may be as, or even more important than Curcumin itself (Aggarwal, 2013), meaning that isolating one phytochemical may not be the best approach as doing so may exclude the potential benefits from the many other compounds. For example, Turmeric contains at least 300 active components (Aggarwal, 2013) and Curcumin is but one of a group of compounds classified as Curcuminoids (Na, 2013).

Interestingly, some studies suggest that when investigating Turmeric modified to exclude Curcumin, the effects were found  to be just as effective(and sometimes even more effective) as Turmeric with Curcumin(Gupta, 2013²), suggesting there is much more than just Curcumin in terms of nutritive or health value. Other studies evaluating Turmeric versus Curcumin found that Turmeric itself was more potent in terms of anti-cancer activity (Gupta, 2013²)  We have seen this happen frequently when a chemical in a plant is isolated and given in doses well above what is naturally found in nature, to no added benefit.

Utility of isolating one compound versus the whole food

We have many examples of supplement companies magnifying concentrations of nature’s phytochemicals or vitamins or minerals with little success in terms of health benefit but great success financially. Two prominent examples:

·       Antioxidant supplements do not fare as well compared to when consumed as a whole food, mainly because the process of absorption is complex and involves other factors found in the food, rather than the antioxidant itself. The equal amount of Vitamin C found in an apple, if given as a supplement has far less antioxidant power than from just eating the apple itself. The antioxidant ability from Vitamin C in the apple was 263 times more potent than when vitamin C was isolated and tested by itself (Eberhardt, 2000). Most trials investigating single antioxidant supplements for risk reduction of most of our majors diseases have been unsuccessful (NCCIH. 2013).

·       Fish oil supplements, a processed oil, stripped of the other macronutrients, phytochemicals and other nutrients found in fish have not been found to useful for many disease states, is no longer considered useful for primary or secondary cardiovascular disease, and has not shown a meaningful effect to reduce cancer incidence, non-vascular death, or total mortality (Turgeon, 2015; Zhang YF 2014; Rizos EC, 2017; Abdelhamid, 2018). Additionally, a meta-analysis of studies using long term Omega 3 fish oil supplements was found to increase risk of atrial fibrillation (Gencer, 2021). This pooled analysis included trials providing lower intakes of DHA at 380mg/day which when combined suggested a 12% increased risk for trials using low DHA doses.  Another study (UK Biobank) also confirmed this in healthy populations with no cardiovascular disease in which regular use of fish oil supplements resulting in no primary prevention benefit and instead an increased risk for atrial fibrillation and also stroke (Chen, 2024).   Importantly, the American Heart Association highlights the heart-brain axis in their Scientific Statement that atrial fibrillation may compromise cerebral blood flow potentially damaging small blood vessels in the brain and creating microhemorrhages instrumental to cognitive function (Testai, 2024). A meta-analysis suggested a twice-fold increase risk for dementia in those with AF (Kwok, 2011)  while another suggested a 1.4 to 2.2 fold increase risk for dementia or cognitive impairment and increases in white matter hyperintensities and decreased cerebral perfusion and cerebral volume (Koh, 2022; Papanastasiou, 2021).

·       Algae oil supplements.  As fish and therefore fish oil derive their Omega 3 fatty acids from algae, it is unknown whether algae supplements will reveal the same findings seen from fish oil supplements, though similar to fish oil supplements, algae oil  supplements in several studies showed  increases in LDL Cholesterol which could affect CHD Risk (Bernstein, 2012; Sanders, 2014).

Possible hazards when supplements are formulated well above naturally occurring levels

Other examples (which are not formulated for increased bioavailability) suggest risks when doses or amounts greatly exceed what is needed in human health:

·       Increasing the normal dosage of Iron as a vitamin supplement can carry significant side effects, as mentioned by the National Institutes of Health, and often iron only supplement manufacturers formulate supplements at double or triple or even more than the recommended levels are set at. As the NHS fact sheet mentions, the body has no way to excrete iron (except for women during some life stages), and health risks including unintentional poisoning can occur.   Excessive intakes or iron or high levels in the body can also carry long term health risks, and is associated with greater risk for colorectal cancer, cardiovascular disease, infections,  neurodegenerative,  inflammatory and other diseases, and may be implicated in breast cancer formations (Geissler, 2011; Jian, 2012; Kabat, 2007).

·       Similar to Curcumin in Turmeric, other active components found in nature, such as from various types of chili and cayenne peppers, and other pepper plants/seeds have been investigated. Capsaicin, the main compound from the capsaicinoid family, responsible for the spicy taste when eaten, have proved to be a cautionary example. When taken at low doses, several beneficial health effects have been demonstrated; while at high doses, an increase in ulcers and increased risk for several cancers has been suggested (Rollyson WD, 2014).

·       Roughly 20 years ago in a major research trial which has now become a hallmark example that is covered in nutrition and public health courses, beta carotene and vitamin A in mega doses was given to men and women at high risk lung cancer  in an attempt to reduce cancer incidence. This was because fruits and vegetables which contain these nutrients were suggested to reduce lung cancer in observational studies. Not only was there no health or protective effect, the reverse happened, and the participants had increased cancer and mortality, resulting in the immediate cessation of the study (Omenn GS, 1996).   Several other studies continuing to test the antioxidant supplements also failed. See this video

·       Randomized trials using supplements, particularly Vitamin B-6 pyridoxine) as doses much higher than the Redommended Daily Allowance showed a significant increased risk for hip fracture (Garcia Lopez, 2017).

Pattern of isolating nutrients from naturally occurring herbs and spices

What is next? It is likely that companies will continue to focus attention in the same  reductionist manner ie. taking the volatile oils out of cinnamon, or active phytochemcials out of cumin, or ginger and other spices that are gaining in popularity, and ramping up the amount to create supplements in levels far greater than found in nature.  Concern by some researchers has already expressed over the many products that exist with various absorption levels for Turmeric and Curcumin, as well as uncertainly over which formulations may or may not enhance the absorption of individual curcuminoids besides Curcumin (Douglass, 2015).  These concerns have prompted some researchers to suggest that it is now time to form a new standard for rating these products (Douglass, 2015).

Who really is profiting, consumers or companies?

The lack of sufficient clinical trials to support the overwhelming favorable laboratory or animal model outcomes has not stopped the public from jumping on the superfood bandwagon regarding Turmeric or Curcumin.  Who stands to profit from isolating phytochemicals from various spices such as Turmeric and modifying them to be more bioavailable?  The available evidence does not suggest consumers are. Rather, supplement companies who include it and advertise it in their formulations as well as parent manufacturing companies, who will patent it and stand to reap significant financial gain. In briefly searching online, I noted one variety, Longvida® Optimized Curcumin, was selling for $60 per bottle and 65x more bioavailable, and websites proclaim similar supplements as being 285x more bioavailable.

There is no way to reap significant profit from selling food or spices, and is probably one reason why far fewer clinical trials exist for foods and spices than for other products. But if it is modified and patented, then a financial avenue is created, but in the case of a patented more bioavailable form of Curcumin, it needs to be properly tested against what exists already in order to determine any potential increase in efficacy or true benefit.

Elephant in the room

There is strong public health interest in naturally occurring plant based remedies (Epstein, 2010) and consideration of spices for as a therapeutic agent is deserving of attention. However, from a prevention perspective, as Dietitians know fully well, it is  important to recognize that the health crisis in our society and epidemic of chronic disease is not because our supplements are strong enough, but rather (in addition to other lifestyle choices) are from consistently not meeting intake recommendations for those foods that promote health, as well as consistent over consumption of foods that carry known health risks. 

Roughly half of Americans take dietary supplements (Bailey, 2011) despite some of the top selling vitamin supplements having little benefit for most healthy individuals (Guallar, 2013; Fortmann, 2013) and additionally  increasing risk for excessive intakes for those who consume them (Rock, 2007; Timbo, 2006). Less than 10% of our population however, meets the recommended intake for fruits and vegetables,  just 6-8% percent do. Surely little profit is to be gained by helping consumers to increase their intakes of fruits and vegetables and it is certainly perceived as easier to ingest pills than increase specific foods in our diet. Focusing in on improving this alone would do far more in terms of health benefits than any supplement or combination of supplements.  Any continued focus on pills and supplements just furthers the pill solution mentality already engrained in our society, and concomitantly drives us further away from focusing on what really matters: the choices we put on our food plate, and how often engage in physical activity.

Conclusions

With few exceptions, Dietitians know that the best route for obtaining nutrients is through food, rather than supplements.  If a patient wants advice on whether to take Turmeric, the current research does not support recommending the more bioavailable forms of Curcumin, and  recommending Curcumin supplements may not allow for other components found in Turmeric which may possibly be more healthful that Cucurcmin itself.  For these reasons, the best approach may be to recommend  Turmeric n whole form, similar to how it has been used in Ayurvedic medicine for ages and more clinical trials are still needed to support whether this spice is indeed deserving of its superfood status.

For those wishing to increase levels for possible greater benefit, recommend consuming a little bit more each day, or better still, eat the root which is increasingly becoming more available at grocery and health stores, or combine with other natural spices, like black pepper (curry powder contains both) where absorption is a bit better, naturally. Easy enough, and won’t cost your patients $60 a bottle.

Dr. Radak graduated with a masters and doctorate in public health nutrition with a specialty in vegetarian nutrition and has been a Registered Dietitian for over 25 years. He currently coordinates the PhD in Public Health program in the College of Health Sciences and Public Policy at Walden University  as well as teaching public health courses for the program, and is a frequent writer on public health and nutrition topics.

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