Unquestionably, turmeric—or more specifically its primary bioactive compound, curcumin—is one of the most popular nutraceuticals in use today. In fact, a study1 by Grand View Research, Inc. indicates that the global curcumin market will reach $94.3 million by 2022. This is consistent with Global Market Insights,2 whose data predicts that the global curcumin market will exceed $100 million by 2024. But why is curcumin so popular? Simply put, it is highly efficacious, and the research on it is extensive. That being said, some forms of curcumin have significantly more research to support their efficacy than others. Perhaps the most well researched form is curcumin phytosome.

But before jumping into a discussion on curcumin phytosome, here is a little background on turmeric and curcumin.

Turmeric/Curcumin Background and Bioavailability Issues

A member of the ginger family, turmeric has been used for as a traditional remedy in Chinese and Indian ayurvedic medicine as well as for condiment and flavoring purposes for more than 2,000 years, based on records dating back to 600 BCE.3 In the textbook, Bioactive Food as Dietary Interventions for Arthritis and Related Inflammatory Diseases,4 Togni and Appendino indicate that, “the use of turmeric in Indian folk medicine is one of a veritable panacea, apparently efficacious for conditions that we would nowadays classify in the realm of infectious, inflammatory, metabolic and immunological diseases.”

The medicinal part of turmeric is its rhizome, the underground stem that looks more like a root due to its thick appearance. Turmeric’s rhizome contains a variety of natural compounds such as protein, fat, minerals and carbohydrates. Its primary active constituent comprising 0.3-5.4 percent of raw turmeric is the flavonoid curcumin (diferuloylmethane), which is responsible for the plant’s yellow color and the compound providing most of its medicinal qualities. Demethoxycurcumin and bisdemethoxycurcumin are two other major curcuminoids, although a significant body of modern scientific research documents the health benefits of curcumin.5

The limiting factor with curcumin is its poor biovailability—with 40 to 75 percent of curcumin passing through the digestive tract unchanged in animal research.6 Due to its fast metabolic turnover in the liver and intestinal wall, blood concentrations of curcumin are low and tissue distribution is limited following oral dosing.7-15 Maximum plasma curcumin concentrations in humans, even upon intake of doses as high as 10 or 12 g curcumin, remain in the low nanomolar range (<160 nmol/L).16 Hence the value of a delivery system for curcumin, in the form of curcumin phytosome.

Curcumin Phytosome

Phytosomes are made up by lecithin phospholipids from sunflower or soy sources. Curcumin phytosome is not a mixture of curcumin and the phospholipid, but rather a dispersion of curcumin into the phospholipids—like the way that mayonnaise is not a mixture of oil and egg yolk, but rather a dispersion of egg yolk into an oily phase. The significance of this is that phytosomes can optimize the delivery of curcumin and other polyphenolics through the gastrointestinal tract. The result is improved absorption.

This was demonstrated in human research,17 which showed that total curcuminoid absorption was about 29-fold higher for curcumin phytosome (Meriva, Indena) than for ordinary curcumin. Animal research has also shown significantly higher absorption for curcumin phytosome.18 Of course, absorption/ improved bioavailability is all well and good, but the important question to ask is, “Once the curcumin is absorbed, is there evidence of efficacy?” In the case of curcumin phytosome, the evidence of efficacy is truly extensive, and includes treatment for osteoarthritis, bone health, eye conditions, sports performance, fatty liver disease, carpal tunnel syndrome, psoriasis and benign prostatic hyperplasia.

Osteoarthritis

A three-month, human clinical study19 was conducted in which 50 patients with osteoarthritis (OA) either “best available treatment” (as defined by their general practitioner) or best available treatment + 1,000 mg/day curcumin phytosome (Meriva, Indena), providing 200 mg of curcumin. The results were the following improvements in the curcumin phytosome group:

• The global WOMAC score (i.e. pain and stiffness) decreased by 58 percent (P<0.05), compared to 2 percent in the control group.

• Walking distance in the treadmill test was prolonged from 76 m to 332 m (P<0.05), compared to 82 m to 129 in the control group.

• CRP (inflammatory marker) levels decreased from 168 +/- 18 to 11.3 +/-. 4.1 mg/L in the subpopulation with high CRP, compared to 175 +/- 12.3 to 112 +/- 22.2 mg/L in the control group. • Treatment costs (use of anti-inflammatory drugs, treatment and hospitalization) were reduced significantly in the curcumin phytosome group.

In a second, controlled, eight-month study,20 100 OA patients also received 1,000 mg/day curcumin phytosome (Meriva, Indena), corresponding to 200 mg curcumin/day). The results were that pain, stiffness and physical function improved significantly (p<0.05) in the curcumin phytosome group compared to the control group (see table).

In addition, the treadmill tests indicated an improvement of 34 percent from the baseline initial distance (p<0.05) after eight months with curcumin phytosome, compared to 89 percent in the control group. Likewise, curcumin phytosome induced a statistically significant reduction of all markers of inflammation (sCD40L, IL-1β, IL-6, sVCAM-1, and ESR), while the control group had only marginal and nonsignificant effects on all parameters. Most relevant is that curcumin phytosome decreased use of NSAIDs and other painkillers by 63 percent compared to 12 percent in controls (p<0.05).

In a third study,21 15 patients with various types of pain, including osteoarthritic pain, neuropathic pain (neuralgia, low back pain), recurrent headache, muscular pain (contractions, sport injuries), and dental pain, received 2,000 mg/day of curcumin phytosome (Meriva, Indena), providing 400 mg of curcumin to compare effects with acetaminophen and a nonsteroidal anti-inflammatory drug (nimesulide). Results were that curcumin phytosome showed clear analgesic activity, comparable with 1,000 mg of acetaminophen, but lower than that of a therapeutic dose of nonsteroidal anti-inflammatory drug. Gastric tolerability was significantly better with curcumin phytosome than that of the other medications.

In a four-month observational study,22 patients with knee OA were administered either 500 mg/day curcumin phytosome (Meriva, Indena) + 500 mg/day glucosamine HCl, or 830 mg/day glucosamine HCl + 800 mg/day chondroitin sulfate. Results were that curcumin phytosome + glucosamine had significantly higher Karnofsky Index (assessment tool for functional impairment) and WOMAC score (both in the physical and emotional domains), compared to the chondroitin + glucosamine group. It is also noteworthy that the walking distance at the treadmill test after one month was also significantly higher in the curcumin phytosome plus glucosamine group.

Bone Health

Although most readers will be familiar with osteoporosis, less are familiar with osteopenia, a chronic bone condition characterized by decreased calcification, density, or bone mass. If left untreated, it can lead to osteoporosis and bone fractures. Since in-vitro and animal studies have associated curcumin with improved bone mineral density and mechanical properties, a 24-month, controlled human clinical study23 was conducted to evaluate the efficacy of 1,000 mg/day curcumin phytosome (Meriva, Indena) in effecting bone density in 57 otherwise healthy subjects with low bone density. The control group (n=28) followed standard management (SM) for low bone density, and the active group (n=29) followed SM plus curcumin phytosome. The results showed bone densities significantly increased during the study in supplemented subjects, reaching as high as 7.1 percent. It is noteworthy that no significant changes bone density occurred with SM alone. In conclusion, this preliminary study suggests that curcumin phytosome supplementation in combination with an appropriate lifestyle could be beneficial in the prevention and management of osteopenia.

Eye Conditions

Given curcumin’s success as an anti-inflammatory agent, a study24 was conducted to evaluate the efficacy of 600 mg, twice daily of curcumin phytosome (Meriva, Indena) as an adjunctive treatment for recurrent anterior uveitis (a term describing a group of inflammatory diseases that produces swelling and destroys eye tissues) of different etiologies, in 106 patients who completed a 12-month follow-up therapeutic period. Results were that curcumin phytosome reduced relapse frequency in all treated patients (P < 0.001). In addition, curcumin phytosome was well tolerated and could reduce eye discomfort symptoms and signs after a few weeks of treatment in more than 80 percent of patients. In conclusion, this study demonstrated the potential therapeutic role of curcumin and its efficacy in anterior uveitis, and points out other promising curcumin-related benefits in eye inflammatory and degenerative conditions, such as dry eye, maculopathy, glaucoma, and diabetic retinopathy.

A four-week pilot study25 was conducted to evaluate the effect of 500 mg, twice daily of curcumin phytosome (Meriva, Indena), compared to a control group, on the improvement of diabetic microangiopathy (weak, leaking capillaries) and retinopathy (damage to blood vessels in the retina) in 38 diabetic patients. Results were that, in the curcumin phytosome group, there was a significant improvement in of peripheral microangiopathy (p<0.05) and a decrease in the score of peripheral edema (p<0.05), a sign typically associated with the poor capillary circulation. Likewise, retinal blood flow, retinal edema, and visual acuity also showed improvement with curcumin phytosome; but there were no clinical or microcirculatory improvements in controls. In conclusion, curcumin phytosome has value in the management of diabetic microangiopathy and retinopathy. In addition, a group of researchers conducted another study26 in 25 patients with diabetic microangiopathy using the same dose of curcumin phytosome, with similar, and statistically significant results.

An open-label study27 was conducted to investigate the effect of 600 mg, twice daily of curcumin phytosome (Meriva, Indena) on visual acuity and retinal thickness in 18 eyes from 12 patients with acute or chronic central serous chorioretinopathy (a condition where fluid builds up under the retina, distorting vision). Results were that, after six months of therapy, 0 percent of eyes showed reduction in visual acuity, 39 percent showed stabilization, and 61 percent showed improvement. The improvement was statistically significant (P = 0.08). After six months of therapy, 78 percent of eyes showed reduction of neuroretinal or retinal pigment epithelium detachment, 11 percent showed stabilization, and 11 percent showed an increase. A follow-up study28 showed similar, and statistically significant results.

The meibomian glands (also called tarsal glands) are a special kind of sebaceous gland at the rim of the eyelids, responsible for the supply of meibum, an oily substance that prevents evaporation of the eye's tear film. Dysfunction of meibomian glands (MGD) is among the most frequent causes of ocular discomfort. Since inflammation plays a major role in meibomian gland dysfunction, a three-month study29 was conducted with 12 affected patients to analyze the effectiveness of supplementation with 1 g/daily curcumin phytosome (Meriva, Indena) in improving tear stability and in reducing inflammatory symptoms and signs due to meibomian gland dysfunction. Results were that tear instability (defined as tear breakup time), Quality of Life Test, interpalpebral corneal dye staining and lid margin inflammation all improved.

Sports Performance

To test whether 1 g twice daily of curcumin phytosome (Meriva, Indena), or placebo, could reduce damage from oxidative stress and inflammation related to acute muscle injury induced by eccentric continuous exercise, a randomized, placebo-controlled, single-blind pilot trial30 was conducted with 20 healthy, moderately active male volunteers. Supplementation was initiated 48 hours prior to a downhill running test and was continued for 24 hours after the test (four days in total). Muscle damage was quantified by MRI and analyses on muscle samples obtained 48 hours after the test. Patient-reported pain intensity was also recorded. Results were that subjects in the curcumin group reported less pain in the lower limb as compared with subjects in the placebo group, with significant differences in the right and left anterior thighs. Significantly fewer subjects in the curcumin group had MRI evidence of muscle injury in the posterior or medial compartment of both thighs. Increases in markers of muscle damage and inflammation tended to be lower in the curcumin group, with significant differences observed for interleukin-8 at two hours after exercise. In conclusion, curcumin phytosome has the potential for preventing delayed onset muscle soreness (DOMS), as suggested by its effects on pain intensity and muscle injury.

Additional evidences for curcumin phytosome in muscular well-being are available. In fact, a recent study31 evaluated the effects of curcumin phytosome (Meriva, Indena) supplementation in limiting the onset and the progression of sarcopenia, in 86 otherwise healthy elderly subjects > 65 years with apparent loss of strength and tiredness. The subjects freely decided to start one of the following interventions: 1) standard management (exercise, balanced diet including proteins); 2) standard management + 1 g/day curcumin phytosome; or 3) standard management + 1 g/day curcumin phytosome + other supplementation (vitamin D 800 IU/day; vitamin C 500 mg/day; isoleucine 3 g/day; carnitine 1 g/day). A number of functional and biochemical parameters were evaluated at baseline and after three months (hand grip, weight lifting, time/distance before feeling tired after cycling, walking and climbing stairs; general fitness, proteinuria, oxidative stress, functional impairment scale; left ventricular ejection fraction). Results were significant improvements in all parameters, with respect to baseline values, were observed in the two supplementation groups (p < 0.05), with no improvement in the standard management-only group. At three months, inter-group comparison revealed a statistical advantage in all parameters for both supplementation groups compared with the standard management-only group (p < 0.05). In conclusion, the addition of curcumin phytosome, either or not combined with other dietary supplements, to standardized diet and exercise plan contributes to improve strength and physical performance in elderly subjects, potentially preventing the onset of sarcopenia.

Another study with curcumin phytosome (Meriva, Indena) was undertaken since endurance exercise increases the production of the inflammatory IL-6 cytokine, and is thought to impair intracellular defense mechanisms—and in-vitro research has indicated that curcumin may help inhibit cytokine production. In this study,32 11 male recreational athletes (consuming a low carb diet) consumed a single 500 mg of dose of curcumin phytosome with midday meal for three days, and then 500 mg was ingested just before exercise to investigate the effect of supplementation on the cytokine and stress responses following two hours of cycling. Results were that curcumin phytosome appeared to lower the concentration of IL-6 released one hour following exercise when compared to placebo, although the difference did not reach statistical significance (which may have been due to the small study size). Nevertheless, participants reported “better than usual” scores in the subjective assessment of psychological stress when supplementing with curcumin, indicating that they felt less stressed during training days (p = 0.04) compared to placebo.

Exercise-heat stress increases gastrointestinal barrier damage and the risk of exertional heat stroke. Over the past decade at least eight different dietary supplements have been tested for potential improvements in gastrointestinal barrier function and systems-level physiology responses during exercise-heat stress, but none have been shown to protect against both insults simultaneously. To investigate the effect of three days of supplementation with 500mg/day curcumin phytosome (Meriva, Indena) on gastrointestinal (GI) barrier damage and systems-physiology responses to exertional heat stress, eight participants ran (65 percent VO2max) for 60 minutes in an environmental chamber (98.6 degrees Fahrenheit/25 percent relative humidity) two times—once after three days of supplementation with curcumin phytosome, and once after three days with placebo. There were two major results from this study. First, curcumin phytosome supplementation reduced the rise in certain physiology parameters during exertional heat stress. Second, these changes were accompanied by reductions in GI barrier damage and associated inflammatory cytokine responses. Collectively, these data suggest that short-term supplementation with curcumin phytosome may help to lower exercise-heat stress risk in non-heat acclimated individuals.33

Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases in the general adult population. Cholesterol and triglyceride problems, high uric acid levels, and insulin resistance are common risk factors of NAFLD. Since some research suggest that curcumin has metabolic properties which may be relevant to the treatment of NAFLD, an eight-week controlled study34 was conducted with 87 NAFLD patients to assess the effects of 1,000 mg/day curcumin phytosome (Meriva, Indena). All patients received dietary and lifestyle advises before the start of trial. Anthropometric measurements, lipid profile, glucose, insulin, glycated hemoglobin and uric acid concentrations were measured at baseline and after eight weeks of follow-up. The results were that supplementation with curcumin phytosome was associated with a reduction in serum levels of total cholesterol (P < 0.001), low-density lipoprotein cholesterol (P < 0.001), triglycerides (P < 0.001), non-high-density lipoprotein cholesterol (P < 0.001), and uric acid (P < 0.001), whereas serum levels of high-density lipoprotein cholesterol and glucose control parameters remained unaltered. In conclusion, curcumin phytosome supplementation reduced serum lipids and uric acid concentrations in patients with NAFLD.

Subsequently, a second study35 of the same length was conducted on NAFLD, using the same number of subjects and the same dose of curcumin phytosome. All patients received dietary and lifestyle advises before the start of trial. Anthropometric measurements, hepatic enzymes and liver ultrasonography were assessed at baseline and after eight weeks of follow-up. Results were that supplementation with curcumin phytosome was associated with a reduction in body mass index of -0.99 vs. only - 0.15 in the placebo group (p=0.003). Waist circumference deceased -1.74 cm in the curcumin phytosome group vs. -0.23 cm in the placebo group (p=0.024). Liver ultrasound findings were improved in 75 percent of subjects in the curcumin phytosome group, while the rate of improvement in the control group was only 4.7 percent (p<0.001). Serum levels of aspartate aminotransferase and alanine aminotransferase (enzymes that are typically increased in NAFLD) were reduced by the end of trial in the curcumin group phytosome (p<0.001) but elevated in the control group (p<0.001).

Carpal Tunnel Syndrome

A study36 was conducted to investigate the clinical usefulness of supplementation with 1,000 mg/day curcumin phytosome (Meriva, Indena) in combination with alpha-lipoic acid, and B vitamins in 180 patients with carpal tunnel syndrome (CTS), who were scheduled to undergo surgical treatment. Patients in Group A served as controls and did not receive any treatment either before or after surgery. Patients in Group B received oral supplementation twice a day for three months both before and after surgery (totaling six months of supplementation). Patients in Group C received oral supplementation twice a day for three months before surgery only. Results were that patients in Group B showed significantly lower nocturnal symptoms scores compared with Group A subjects at both 40 days and three months after surgery (both values). Moreover, patients in Group B had a significantly lower number of positive Phalen’s tests (at diagnostic test for CTS) at three months compared with the other study groups. In conclusion, curcumin phytosome in combination with alpha-lipoic acid and B-vitamins twice a day both before and after surgery is safe and effective in CTS patients scheduled to undergo surgical treatment for CTS.

Psoriasis

This randomized, double-blind, placebo-controlled clinical trial37 was conducted to assess the effectiveness of with 2,000 mg/day curcumin phytosome (Meriva, Indena) in the treatment of psoriasis. Sixty-three patients with mild-to-moderate psoriasis vulgaris were randomly divided into two groups treated with topical steroids and curcumin phytosome (arm 1), or with topical steroids alone (arm 2), both for 12 weeks. At the beginning and at the end of the therapy (week 12), clinical assessment and immunoenzymatic analysis of the serum levels of IL-17 and IL-22 were performed. At week 12, both groups achieved a significant reduction of PASI values. However, that value was higher in patients treated with both topical steroids and oral curcumin than in patients treated only with topical steroids. Moreover, IL-22 serum levels were significantly reduced in patients treated with curcumin phytosome. In conclusion, curcumin was demonstrated to be effective as an adjuvant therapy for the treatment of psoriasis vulgaris and to significantly reduce serum levels of IL-22.

Benign Prostatic Hyperplasia

The aim of this study38 was to compare two management plans in the treatment of 61 men with symptomatic benign prostatic hyperplasia (BPH). One management plan was based on a currently validated standard treatment (defined as the best standard management [BSM]), and the other was BSM + treatment with 1,000 mg/day of curcumin phytosome (Meriva, Indena). Signs and symptoms were evaluated using the International Prostate Symptom Score (IPSS). Results were that all IPSS scores, with the exception of the stream weakness score in the BSM group, were improved (p<0.05 vs. inclusion) in both groups. The overall results in the curcumin phytosome group were significantly better than in the BSM-only group (p<0.05). No side effects were recorded. The quality of life improved in both groups but was significantly better in the curcumin phytosome group (p<0.01). There was also a significantly greater decrease in clinical and subclinical episodes of urinary infections and urinary block in the curcumin phytosome group (p<0.01). In conclusion, the addition of curcumin phytosome to BSM treatment contributed to the reduction of signs and symptoms of the disease without causing any significant additional side effect.

Conclusion

Curcumin is a popular dietary supplement, and its popularity shows no signs of abating according to sales projections. Given issues with poor bioavailability, however, it is important to choose a form of curcumin shown to have better absorption. Furthermore, it is important to verify the efficacy, as well as the bioavailability of the curcumin being used. Research has shown that curcumin phytosome (Meriva, Indena) has very good bioavailability, and has efficacy in the treatment of osteoarthritis, bone health, eye conditions, sports performance, fatty liver disease, carpal tunnel syndrome, psoriasis and benign prostatic hyperplasia. VR

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Gene Bruno, MS, MHS, the dean of academics for Huntington College of Health Sciences, is a nutritionist, herbalist, writer and educator. For more than 30 years he has educated and trained natural product retailers and health care professionals, has researched and formulated natural products for dozens of dietary supplement companies, and has written articles on nutrition, herbal medicine, nutraceuticals and integrative health issues for trade, consumer magazines and peer-reviewed publications. He can be reached at gbruno@hchs.edu.