Vitamin D May Reduce Falls in Elderly Nursing Home Residents

January 29, 2010 — Vitamin D supplementation and pharmacist review of medications may help reduce falls in elderly nursing home residents, according to the results of a systematic review reported online January 20 in the Cochrane Database of Systematic Reviews.

“Falls in nursing care facilities and hospitals are common events that cause considerable morbidity and mortality for older people,” write Ian D. Cameron, MBBS, PhD, from Sydney Medical School, the University of Sydney in Ryde, Australia, and colleagues.

The goal of this review was to determine the efficacy of interventions aiming to reduce falls by older people in nursing care facilities and hospitals. The reviewers searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (January 2009); the Cochrane Central Register of Controlled Trials (The Cochrane Library 2008, Issue 2); MEDLINE, EMBASE, and CINAHL (all to November 2008); trial registers; and bibliographies of retrieved articles.

Criteria for inclusion in the review were randomized controlled trials of interventions designed to reduce falls in older people in nursing care facilities or hospitals, with main study endpoints of fall rate and the risk of falling. Methodologic quality of the trials was independently evaluated by 2 reviewers, who also extracted and pooled data where appropriate.

There were 41 trials, enrolling a total of 25,422 participants, meeting selection criteria. Findings from 7 trials testing supervised exercise interventions in nursing care facilities were inconsistent. Overall, multifactorial interventions were not associated with a significantly lower rate of falls in 7 trials enrolling a total of 2997 participants or with a lower risk of falling in 8 trials enrolling a total of 3271 participants.

However, multifactorial interventions provided by a multidisciplinary team were associated with lower rate of falls in nursing home residents (rate ratio [RaR], 0.60; 95% confidence interval [CI], 0.51 – 0.72; 4 trials, n = 1651) and risk of falling (risk ratio [RR], 0.85; 95% CI, 0.77 – 0.95; 5 trials, n = 1925), based on a post hoc subgroup analysis.

Vitamin D supplementation in nursing home residents was associated with a lower rate of falls (RaR, 0.72; 95% CI, 0.55 – 0.95; 4 trials, n = 4512) but not with the risk of falling (RR, 0.98; 95% CI, 0.89 – 1.09; 5 trials, n = 5095).

Multifactorial interventions in hospitals for patients with a length of stay of 3 weeks or more were associated with a lower rate of falls (RaR, 0.69; 95% CI, 0.49 – 0.96; 4 trials, n = 6478) and the risk of falling (RR, 0.73; 95% CI, 0.56 – 0.96; 3 trials, n = 4824). In addition, supervised exercise interventions were associated with a significant decrease in the risk of falling (RR, 0.44; 95% CI, 0.20 – 0.97; 3 trials, n = 131).

“There is evidence that multifactorial interventions reduce falls and risk of falling in hospitals and may do so in nursing care facilities,” the review authors write. “Vitamin D supplementation is effective in reducing the rate of falls in nursing care facilities. Exercise in subacute hospital settings appears effective but its effectiveness in nursing care facilities remains uncertain.”

Limitations of this review include those inherent in the selected studies, such as lack of blinding, confounding because of differences in treatment and control groups at entry, differences in underlying care programs, poorly defined inclusion and exclusion criteria and falling events, and differences in ascertainment of falls.

“Falls prevention programmes that include exercises for frail nursing care facility residents should carefully assess each individual’s suitability, as there is the possibility that exercise programmes may increase their risk of falls,” the review authors conclude. “The choice of type of exercises may be important in avoiding an increase in falls. The rate of falls and number of fallers should be monitored before and after adopting an intervention because it might increase falls.”

South Eastern Sydney and Illawarra Area Health Service, Australia; Rehabilitation Studies Unit, Faculty of Medicine, University of Sydney, Australia; University of Otago, New Zealand; National Ageing Research Institute, Australia; and Accident Compensation Corporation, New Zealand, supported this review. The review authors have disclosed no relevant financial relationships.

Cochrane Database Syst Rev. Published online January 20, 2010. Abstract

For more information on falls in the elderly is available from the Centers for Disease Control.
Clinical Context

Older persons in nursing care facilities and hospitals often fall, with possible complications including loss of independence, injury, and even mortality. Effective interventions to prevent falls are important for the health of these individuals as well as for public health and reduction of healthcare costs.

Interventions to lower fall risk should be evidence-based so that staff time and resources are allocated appropriately and so that older persons and their families are not subjected to the stress of ineffective interventions. This review aimed to inform best practice and to identify issues of importance for future research regarding strategies of fall prevention.

Study Highlights

• The objective of this Cochrane review was to examine the efficacy of interventions designed to reduce falls among older people in nursing care facilities and hospitals.
• Literature searched included the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (January 2009); the Cochrane Central Register of Controlled Trials (The Cochrane Library 2008, Issue 2); and MEDLINE, EMBASE, and CINAHL, all to November 2008.
• The reviewers also searched trial registers and references cited in identified articles.
• Selection criteria were randomized controlled trials of interventions designed to lower fall risk in elderly nursing home residents or hospital inpatients, with primary outcomes of fall rate and the risk of falling.
• 2 reviewers independently examined trial quality and extracted data, which were pooled when feasible.
• Inclusion criteria were met by 41 trials with a total of 25,422 participants.
• For supervised exercise interventions in nursing care facilities, 7 trials yielded inconsistent results.
• Overall, multifactorial interventions in nursing care facilities did not reduce fall rate in 7 trials (total n = 2997) or risk of falling in 8 trials (total n = 3271).
• A post hoc subgroup analysis showed that multifactorial interventions provided by a multidisciplinary team were associated with lower fall rate (RaR, 0.60; 95% CI, 0.51 – 0.72; 4 trials, n = 1651) and risk of falling (RR, 0.85; 95% CI, 0.77 – 0.95; 5 trials, n = 1925) in residents of nursing care facilities.
• In residents of nursing care facilities, vitamin D supplementation was associated with decreased fall rate (RaR, 0.72; 95% CI, 0.55 – 0.95; 4 trials, n = 4512).
• However, vitamin D supplementation did not reduce the risk of falling in residents of nursing care facilities (RR, 0.98; 95% CI, 0.89 – 1.09; 5 trials, n = 5095).
• In nursing care facilities, a clinical medication review by a pharmacist appeared to be effective in reducing the rate of falls.
• In hospitals, multifactorial interventions for patients with length of stay of 3 weeks or more were associated with a lower rate of falls (RaR, 0.69; 95% CI, 0.49 – 0.96; 4 trials, n = 6478) and risk of falling (RR, 0.73; 95% CI, 0.56 – 0.96; 3 trials, n = 4824).
• However, the reviewers could not make recommendations regarding any particular component of these multifactorial intervention programs.
• Supervised exercise interventions in hospitals were associated with a significant reduction in the risk of falling (RR, 0.44; 95% CI, 0.20 – 0.97; 3 trials, n = 131).
• The reviewers concluded that multifactorial interventions reduce falls and the risk of falling in hospitals and may do so in nursing care facilities.
• They also concluded that vitamin D supplementation effectively reduces the rate of falls in nursing care facilities.
• Although exercise in subacute hospital settings appears to be effective, it remains uncertain whether it is effective in nursing care facilities.
• Review limitations are those of the included studies, such as lack of blinding, confounding, and poorly defined inclusion and exclusion criteria and falling events.

Clinical Implications

• A Cochrane systematic review shows that for elderly persons in nursing care facilities, vitamin D supplementation effectively reduces the rate of falls. A clinical medication review by a pharmacist may also be effective in reducing the rate of falls. However, the value of exercise in reducing fall risk remains uncertain in this setting.
• In hospitals, multifactorial interventions reduce falls and the risk of falling in elderly persons. Exercise in subacute hospital settings also appears to be effective in reducing the risk of falling, based on this Cochrane systematic review.

Source: Medscape CME

Authors:

Laurie Barclay, MD
Freelance writer and reviewer, Medscape, LLC
Disclosure: Laurie Barclay, MD, has disclosed no relevant financial relationships.

Brande Nicole Martin
CME Clinical Editor, Medscape, LLC
Disclosure: Brande Nicole Martin has disclosed no relevant financial information.

Laurie Barclay, MD
Freelance writer and reviewer, Medscape, LLC
Disclosure: Laurie Barclay, MD, has disclosed no relevant financial relationships.

Laurie E. Scudder, MS, NP
Accreditation Coordinator, Continuing Professional Education Department, Medscape, LLC; Clinical Assistant Professor, School of Nursing and Allied Health, George Washington University, Washington, DC; Nurse Practitioner, School-Based Health Centers, Baltimore City Public Schools, Baltimore, Maryland
Disclosure: Laurie E. Scudder, MS, NP, has disclosed no relevant financial relationships.

Association of vitamin B-6 status with inflammation, oxidative stress, and chronic inflammatory conditions: the Boston Puerto Rican Health Study1,2,3

Jian Shen, Chao-Qiang Lai, Josiemer Mattei, Jose M Ordovas and Katherine L Tucker

1 From the Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University Boston MA (JS C-QL JM JMOKLT)the Bouvé College of Health Sciences at Northeastern University Boston MA (KLT).

2 Supported by the National Institutes of Health, National Institute on Aging grant 01AG023394-02 and National Heart, Lung, and Blood Institute grant HL54776; and the US Department of Agriculture, Agricultural Research Service contracts 53-K06-5-10 and 58-1950-9-001.

3 Address correspondence to J Shen, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston, MA 02111-1524. E-mail: jian.shen@tufts.edu.

Background: Low vitamin B-6 status has been linked to an increased risk of cardiovascular diseases. The cardioprotective effects of vitamin B-6 independent of homocysteine suggest that additional mechanisms may be involved.

Objective: Our objective was to examine the cross-sectional association of vitamin B-6 status with markers of inflammation and oxidative stress.

Design: We measured plasma pyridoxal-5′-phosphate (PLP), C-reactive protein (CRP), and an oxidative DNA damage marker, urinary 8-hydroxydeoxyguanosine (8-OHdG), in Puerto Rican adults who were living in Massachusetts (n = 1205, aged 45–75 y).

Results: There was a strong dose-response relation of plasma PLP concentration with plasma CRP. Increasing quartiles of PLP were significantly associated with lower CRP concentrations (geometric means: 4.7, 3.6, 3.1, and 2.5 mg/L; P for trend < 0.0001) and with lower urinary 8-OHdG concentrations (geometric means: 124, 124, 117, and 108 ng/mg creatinine; P for trend: 0.025) after multivariate adjustment. These negative associations persisted after plasma homocysteine was controlled for. Plasma PLP concentrations were significantly correlated with plasma fasting glucose (r = –0.1, P = 0.0006), glycated hemoglobin (r = –0.08, P = 0.006), and homeostasis model assessment of β cell function (r = 0.082, P = 0.005). Metabolic syndrome, obesity, and diabetes were also significantly associated with low plasma PLP concentrations (P = 0.011, 0.0007, and 0.004, respectively).

Conclusions: Low vitamin B-6 concentrations are associated with inflammation, higher oxidative stress, and metabolic conditions in older Puerto Rican adults. Our data suggest that vitamin B-6 may influence cardiovascular disease risk through mechanisms other than homocysteine and support the notion that nutritional status may influence the health disparities present in this population.

Source: American Journal Clinical Nutrition  www.ajcn.org/cgi/content/abstract/91/2/337

What is sustainable healthcare?

Sustainability is a robust concept that has proven its worth across a range of different industries including energy, agriculture, forestry and even construction and tourism.

Contemporary healthcare in western countries is presently dominated by use of pharmaceutical drugs—and most indicators would suggest that these approaches have had very limited value in dealing with some of the greatest scourges facing human health, including chronic diseases, psychiatric diseases and even certain infectious diseases.

From a cost/benefit perspective, pharmaceutical-based approaches to healthcare do not fare favourably and a sea change is required if mainstream western healthcare is to deal with the ever increasing burden on the healthcare system, particularly given that this burden will be exacerbated by an ageing population.

The dichotomy between complementary & alternative medicine (CAM) and orthodox/allopathic healthcare approaches has led to increased vilification of protagonists of each approach. The use of scientific methods of evaluation that do not lend themselves well to CAM approaches have meant that the ‘medical establishment’ has been able to increasingly marginalise CAM approaches. This has occurred while the establishment has provided no significant improvement in its offering to the majority of the population that is either forced to accept or choose to accept pharmaceutical-based medicine as the most effective and scientifically-validated form of medicine.

Encouraging a paradigm shift that requires all forms of healthcare to be bound by principles of sustainability is one of the surest means of providing a level playing field for all healthcare modalities which encourages those approaches that are compatible with the complex biological and energetic systems of which are bodies are comprised.

Sustainability principles, including those applying to engineering and design, should also be applied to healthcare facilities. To read an evaluation of the state-of-the-art on this subject, read an article by Dominic Stalker, a work experience science student who worked with the ANH during the summer of 2008 entitled Engineering sustainability into hospitals.
Definition of Sustainable Healthcare

The ANH first defined sustainable healthcare in 2006 in the UK practitioner journal Nutrition Practitioner. The definition is as follows:

“A complex system of interacting approaches to the restoration, management and optimisation of human health that has an ecological base, that is environmentally, economically and socially viable indefinitely, that functions harmoniously both with the human body and the non-human environment, and which does not result in unfair or disproportionate impacts on any significant contributory element of the healthcare system.”

Read Dr Robert Verkerk’s article published by the Australasian College of Nutritional and Environmental Medicine (ACNEM).

The article was written following an inaugural lecture at the National Institute for Integrative Medicine, hosted by Australian associations ACNEM and AIMA.

Looking through the window—the paradigm shift is the other side of the wall…

Executive Summary of the ANH Sustainable Healthcare Campaign

For more than two decades the orthodox (allopathic or western) healthcare establishment has vigorously attacked the scientific basis, efficacy and safety of the diverse range of modalities befitting approaches that are commonly placed under the banner of complementary and alternative medicine (CAM). Simultaneously, the CAM community, the natural products industry, health freedom organisations and large numbers of consumers and protagonists of CAM, have argued that these attacks are unjustified and have reciprocated by exposing the apparent lack of efficacy and poor safety record of orthodox healthcare.

These differences of opinion are so deep-seated that the polarity between the two contrasting approaches has become increasingly reinforced. The relative lack of resources within the CAM community, the natural products industry and the health freedom movement, by comparison with the pharmaceutical industry and orthodox medical system which it supports, means that it is by and large proving very difficult to improve the acceptability of CAM modalities in mainstream healthcare.

All the available indicators suggest that orthodox healthcare, which is dominated by interventions with new-to-nature pharmaceutical drugs, is not sustainable. ‘Evidence-based medicine’ (EBM) is increasingly being used both as a means of justifying pharmaceutical intervention as the world’s dominant approach to healthcare and its ever-wider application to discredit or even outlaw particular CAM approaches.

The Alliance for Natural Health (ANH) proposes that the application of the principles of sustainability to healthcare may be one of the most effective ways of altering the perception of established and emerging CAM modalities from the vantage point of government authorities and the current medical establishment. In addition, such an approach could significantly assist a transition in mainstream healthcare that is characterised by improved take up of biologically compatible modalities, as found within CAM. Such a transition would, among other things, allow for much greater use of preventative approaches, especially among children, young adults and non-diseased sub-populations, better diagnosis of disease, widespread adoption of lifestyle and nutrition-based approaches, greatly reduced dependence on new-to-nature medications and marked changes in medical training. With the identification of scientifically established criteria for sustainability in healthcare, only those approaches meeting the criteria stipulated would be accepted. Sustainability has become one of the key technological drivers in a range of other industries where social or environmental degradation has been implicated, and it is incongruous that the principles of sustainability have yet to be applied to healthcare.

The ANH, its affiliates and strategic partners are well set to help trigger the transition towards sustainable healthcare. The transition will continue to require funding of independent research in academic institutions, extensive public and government-targeted awareness campaigns and the establishment of scientifically monitored pilot programmes designed to demonstrate both feasibility and sustainability.

A transition towards sustainability would also help to eliminate the existing polarity between orthodox healthcare and CAM approaches and would inevitably prefer those approaches that function harmoniously with biological systems and human metabolism, rather than those that oppose them.

** Sustainable Health aritcles on this page provide by ANH-Europe.

Green Tea May Be Useful at Preventing Prostate Cancer

Johnson JJ, Bailey HH, Mukhtar H. Green tea polyphenols for prostate cancer chemoprevention: a translational perspective. Phytomed. 2010;17: 3-13.

It was estimated that in 2008, approximately 200,000 new cases of prostate cancer (PCa) would be diagnosed, resulting in roughly 30,000 deaths. Worldwide, the highest rates of PCa occur in “the West” (i.e., the United States, Canada, Australia, and Western Europe), and the lowest rates occur in Asia. A variety of genetic and environmental factors are thought to contribute to the development of PCa. It has become increasingly evident that dietary constituents have the ability to “target multiple deregulated signaling pathways while allowing normal processes to continue.” Furthermore, migratory studies have shown that Asian men who move to the United States and adopt a western diet have a greater incidence of PCa than do their native Asian counterparts. Thus, many epidemiologists have suggested that lifestyle and dietary factors play a role in the development of PCa. Asian populations are known to consume large quantities of green tea (Camellia sinensis), and a major constituent of green tea—epigallocatechin-3-gallate (EGCG)—has been shown in cell culture models to decrease cell viability and to promote apoptosis in PCa cell lines but not in noncancerous cell lines and in animal models, to delay the development and progression of PCa. The objective of the present study was to review the available data on the effects of green tea on PCa chemoprevention.

Conflicting results have been observed in epidemiologic studies. Of 6 epidemiologic studies of green tea reviewed, the majority showed a significant decrease in the risk of developing PCa with increasing intakes of green tea; however, other studies showed no significant decrease. EGCG is the most abundant catechin in green tea and has been studied extensively. In preclinical studies, several mechanisms of action for the chemopreventive effects of EGCG have been observed. For example, EGCG has been shown to target inflammatory pathways (e.g., nuclear factor-kappa B and cyclooxygenase-2), MAP kinases, insulin-like growth factor, androgen receptors, and detoxification enzymes. Preclinical pharmacokinetic studies of green tea have shown that the availability of green tea catechins (GTCs) is low (from 2% to 13%) after oral consumption. Many of these studies used a standardized pharmaceutical-grade preparation known as Polyphenon E® (200 mg of EGCG, 37 mg of epigallocatechin, and 31 mg of epicatechin per capsule; Mitsui Norin, Ltd.; Tokyo, Japan); Polyphenon E has been granted investigational new drug (IND) status by the FDA, with each capsule containing 80-98% total catechins by weight, standardized to EGCG that comprises 50-75% of the substance.

N.B. The structure of epicatechin-3-gallate provided in this publication has been inadvertently misrepresented as identical to that of EGCG.

Thus far, three clinical trials on the role of different forms of green tea on the prevention (n = 1) or treatment (n = 2) of PCa have been published.1-3 Two of these trials were conducted in patients with hormone-refractory PCa. The patients were treated with green tea powder (1 g 6 times daily; n = 42) in the study by Jatoi et al1 and with capsules of green tea extract (250 mg twice daily; n = 19) in the study by Choan et al.2 Both studies showed little to no therapeutic effect, although one patient in the study by Jatoi et al had a significant decrease from baseline in his prostate specific antigen (PSA) level, although this effect was not sustained beyond 2 months. Bettuzzi et al3 conducted a randomized clinical trial of the safety and efficacy of green tea in a chemoprevention trial in patients with prostatic intraepithelial neoplasia. Patients received either placebo (n = 30) or 600 mg GTCs (n = 30) daily (three 200-mg capsules); each capsule contained 5.5% epigallocatechin, 12.2% epicatechin, 51.9% EGCG, 6.1% epicatechin-3-gallate (a total of 75.7% GTCs), and <1% caffeine. After 1 year of treatment, 1 patient in the green tea group and 9 patients in the placebo group developed PCa. The total PSA level was not “noticeably” different between the 2 groups of patients. A 2-year follow-up in a subset of these participants showed that the chemopreventive effect of green tea catechins was “long lasting.” The authors conclude that the results of this clinical trial “are encouraging and provide rationale for additional clinical trials evaluating the efficacy of green tea polyphenols as a cancer chemoprevention agent.” A very recent study of the effects of short-term supplementation with the active compounds in green tea (EGCG; Polyphenon E) on serum biomarkers in men with prostate cancer showed a significant reduction in serum levels of PSA, hepatocyte growth factor, and vascular endothelial growth factor and no elevation in liver enzymes.

According to the authors, it has become evident over time that standardized green tea polyphenols should be used, as opposed to green tea infusions, for interventional purposes to ensure the content of polyphenols being investigated. Evidence collected thus far on the effects of green tea polyphenols on PCa prevention and treatment “suggests that green tea may be a promising agent for PCa chemoprevention and further clinical trials of participants at risk of PCa or early stage PCa are warranted.”

—Brenda Milot, ELS

References

1Jatoi A, Ellison N, Burch PA, et al. A phase II trial of green tea in the treatment of patients with androgen independent metastatic prostate carcinoma. Cancer. 2003;97:1442-1446.

2Choan E, Segal R, Jonker D, et al. A prospective clinical trial of green tea for hormone refractory prostate cancer: an evaluation of the complementary/alternative therapy approach. Urol Oncol. 2005;23:108-113.

3Bettuzzi S, Brausi M, Rizzi F, Castagnetti G, Peracchia G, Corti A. Chemoprevention of human prostate cancer by oral administration of green tea catechins in volunteers with high-grade prostate intraepithelial neoplasia: a preliminary report from a one-year proof-of-principle study. Cancer Res. 2006;66:1234-1240.

4McLarty J, Bigelow RL, Smith M, Elmajian D, Ankem M, Cardelli JA. Tea polyphenols decrease serum levels of prostate-specific antigen, hepatocyte growth factor, and vascular endothelial growth factor in prostate cancer patients and inhibit production of hepatocyte growth factor and vascular endothelial growth factor in vitro. Cancer Prev Res. 2009;2(7):673-682.

Source: American Botanical Council, 6200 Manor Rd, Austin, TX 78723
Phone: 512-926-4900 | Fax: 512-926-2345 | Email: abc@herbalgram.org

Turmeric Extract Relieves Pain of Knee Osteoarthritis and Improves Function Comparably to Ibuprofen

Kuptniratsaikul V, Thanakhumtorn S, Chinswangwatanakul P, Wattanamongkonsil L, Thamlikitkul V. Efficacy and safety of Curcuma domestica extracts in patients with knee osteoarthritis. J Altern Complement Med. 2009;15(8): 891-897.

Osteoarthritis (OA), a degenerative joint disorder, is a common cause of disability for both men and women. Although nonsteroidal anti-inflammatory drugs (NSAIDs) are the most common treatment for pain relief associated with OA, they can cause serious adverse side effects that impact gastrointestinal, renal, and cardiac health. Curcumin present in turmeric (Curcuma longa syn. C. domestica) extracts has been reported to have anti-inflammatory and antioxidant properties. These authors, from Mahidol University in Bangkok, Thailand, conducted a study to determine the efficacy and safety of a turmeric extract in reducing pain and improving function in patients with knee OA.

Conducted at Siriraj Hospital in Bangkok from April 2005 to May 2006, the study included adult subjects with primary knee OA according to the American Rheumatism Association criteria. To be included in the study, patients had to have knee pain and radiographic osteophytes and at least 1 of the following characteristics: older than 50 years, suffering from morning stiffness lasting less than 30 minutes, and experiencing crepitus (crackling in joints) on motion. Patients reporting a pain score of ≥ 5 of 10 in a numerical rating scale were recruited.

The patients were asked to discontinue their medications for knee OA 1 week before randomization. All patients were randomly allocated to receive either ibuprofen (400 mg twice daily) or turmeric extract (500 mg curcuminoids 4 times daily) for 6 weeks.

According to the authors, the turmeric extracts were produced by the Thai Government Pharmaceutical Organization under the Good Manufacturing Practices standard. Dried rhizomes of C. longa were ground into powder. The turmeric powder was extracted with ethanol and then evaporated at low pressure to obtain ethanolic extracts containing oil and curcuminoids. The oil was then removed. Each capsule of extract contained 250 mg curcuminoids.

The patients were assessed every 2 weeks. The main outcomes were pain on level walking and pain on stair climbing, measured by a numerical rating scale, and knee functions assessed by the time spent on a 100-m walk and going up and down 10 steps.

All patients had blood tests including complete blood count, liver function, and renal function at week 0 and week 6. At week 6, the patients’ satisfaction with treatment was evaluated by a 5-category scale (high, moderate, little, same, or dissatisfaction).

Of 190 patients screened, 107 were selected for the study; 52 were randomly assigned to the curcuminoid group and 55 to the ibuprofen group. Of those, 45 patients in the curcuminoid group and 46 patients in the ibuprofen group completed the study. Most of the patients were overweight elderly women. The duration of symptoms before entering the trial was approximately 20 months. Half of the patients had bilateral knee OA. At baseline, the mean pain scores on level walking and on the stairs, as well as the time spent on the 100-m walk and on the flight of stairs, were similar between the 2 groups.

The authors report that in both groups, the mean scores of all outcomes at week 6 were significantly improved when compared with the baseline values. For example, from week 0 to week 6, the scores for pain on level walking dropped from 5.3 ± 2.3 to 2.7 ± 2.5 for the curcumin group and from 5.0 ± 1.9 to 3.1 ± 2.3 in the ibuprofen group. There was no significant difference in those parameters between the 2 groups, except that pain on stair climbing was less for those taking curcuminoids (P = 0.016). Also, the curcuminoid group seemed to spend less time on the 100-m walk and going up and down a flight of stairs. No significant differences were found for adverse events between the 2 groups, with dyspepsia (curcuminoids 20.8% and ibuprofen 26.9%) most common. Interestingly, many patients in the curcuminoid extract group who experienced bloating symptoms and passing gas described these symptoms as beneficial gastrointestinal effects, whereas those in the ibuprofen group reported gastrointestinal irritation symptoms.

Regarding satisfaction, most patients rated themselves as having moderate to high satisfaction (91.1% in the curcuminoid group and 80.4% in the ibuprofen group). The patients’ satisfaction with treatment was not statistically significantly different (P = 0.15) between the groups. The patients in the ibuprofen group had better compliance to the treatment regimen than those in the curcuminoid extract group (90.1% versus 82.8%, P = 0.001). This finding was attributed by the researchers to the fact that ibuprofen was given twice a day, whereas curcuminoid extract had to be taken 4 times a day.

These results suggest that curcuminoid extracts of turmeric might be as effective as ibuprofen in alleviating knee pain and improving knee functions, with a trend toward a greater effect in patients receiving curcumin extracts. However, the wide range of 95% confidence interval (CI) indicated that the study had an inadequate sample size. Based on the standard deviation (SD) of 2.36, the proper sample size should be 70 patients per group. The authors recommend more studies with an adequate sample, a higher dose of ibuprofen in the comparison group, and double-blind technique to demonstrate the efficacy of turmeric extracts in alleviating knee pain and improving knee function.

―Shari Henson

Source: American Botanical Council, 6200 Manor Rd, Austin, TX 78723
Phone: 512-926-4900 | Fax: 512-926-2345 | Email: abc@herbalgram.org

Healing Properties of Saffron

Ferrence S, Bendersky G. Therapy with saffron and the goddess at Thera Perspectives in biology and medicine. 2004;47(2):199-226.

In approximately the mid-17th century, a devastating volcanic eruption buried the town of Akrotiri on the Greek island of Thera. In 1967, the excavation of the town under the auspices of the Archeological Society of America revealed many well-preserved wall paintings and frescoes, which were cleaned and conserved. The frescoes uncovered at this site ‘suggest that the Therans of ancient Akrotiri developed saffron (Crocus sativus) as a versatile medicine more than 3,600 years ago.’ The interpretation of the meaning of one of these frescoes, found in a building known as Xeste 3, is the subject of this article.

The Xeste 3 frescoes span two adjacent walls and, in one section, portray an elevated, jewelry-clad, woman (goddess) surrounded by animals and young girls in a landscape of crocuses (Crocus spp.). A basket of saffron sits at the feet of the goddess. A blue monkey is depicted extending crocus blooms to the goddess, whereas the girls in the frescoes are picking crocus blooms, carrying crocus blooms, or emptying crocus blooms from a small basket into a large basket on the ground. In another portion of the frescoes, a woman is seen extending one hand toward her bleeding foot as two crocus stigmas fall toward her foot. The artist of this painting depicted the female reproductive portion of the plant—the stigma—in elaborate detail. Although some scholars have interpreted the painting to represent fertility rituals, marriage ceremonies, or local industry, most researchers conclude that ‘crocuses and saffron are at the heart of the matter.’ The authors of this article propose that ‘the program of Xeste 3 does not merely include the secondary medicinal value of saffron as a secondary element, but, in fact, emphasizes its primary therapeutic function, and exhibits the production sequence in cultic recognition of its precious curative value.’

The focus of the Xeste 3 frescoes appears to be the women and the crocuses, which are linked to the healing properties of saffron. The Aegean crocus (Crocus cartwrightianus) is the species depicted, which is an autumnal flower with three large crimson stigmas that can be picked, dried, and ground to make saffron. Of the many medicinal plants developed in the ancient Near East and Mediterranean, saffron has had the greatest number of applications over nearly four millennia. The proven safety, efficacy, and availability of saffron for a large variety of symptoms may be the reason for its prominent portrayal in the Xeste 3 frescoes. The authors ‘hypothesize that the frescoes express a divinely encouraged concept: the medicinal healing that is the major function of the crocus/saffron.’ This hypothesis is based on three observations: the crocus and its stigma are the dominant motif; the medicinal phytoactivity of crocuses is concentrated in the stigma; and the closeness of the basket of saffron to the goddess (which indicates the importance of this substance). Ancient Eastern Mediterranean healers and worshipers often invoked the help of a deity to potentiate a medicine; therefore, the painting may promote the belief that the goddess depicted has conferred curative properties to the saffron or has given the gift of saffron to humans. Thus, it may be interpreted that the introduction of saffron as a medicine may have originated at Akrotiri.

The first known mention of saffron (azupiranu) is in an Assyrian dictionary of botany written in 668-633 BCE, in which it is described as being used to treat dyspnea (breathing difficulty), painful urination, menstrual disorders, and ‘diseases of the head.’ Following the Bronze Age, the use of saffron for medicinal purposes has continued up to the present day. Saffron also has a history of use for the treatment of cutaneous ulcers, wounds, thrush, palpitations, smallpox, measles, jaundice, constipation, eye diseases, liver diseases, joint pain, earaches, diarrhea, vomiting, and headaches. In addition, saffron has long been valued for its effectiveness in treating gynecological conditions. Saffron concoctions have been used to regulate menses and fertility and to induce abortions. Studies conducted since the early 20th century have identified steroidal estrogens and non-steroidal substances in saffron that mimic female sex hormones. In the late 20th and early 21st centuries, saffron or its derivatives (e.g., crocin and crocetin) were shown to have antitumor activity against different malignancies in humans and animals both in vivo and in vitro. Only in the past few decades, however, has the ‘potential success’ of saffron in the treatment of many of the abovementioned conditions been confirmed by phytochemical studies and experimental evidence.

The dominant portrayal of saffron in the Theran frescoes of Akrotiri likely implies that this culture had discovered medicinal uses for saffron. The women participating in the saffron activities in the frescoes ranged in age from young girls to older women. ‘This multi-generational spectrum is consistent with the age range appropriate for diseases extending from menstrual disorders to malignancy.’ On the basis of both modern pharmacology and ancient medical texts, however, saffron therapy is generally efficacious for non-reproductive-related problems as well and for disorders experienced by male patients. The Xeste 3 frescoes appear to ‘anthropomorphize the medicinal plant [saffron] into the persona of a female divinity of medicine.’ Betancourt1 suggests that the Theran artist who created the frescoes ‘created a powerful, unified composition that contains ‘the first true perspective in ancient wall painting’.’

—Brenda Milot, ELS

Reference
1Betancourt PP. Concept of space in Theran compositional systemics. In: Sherratt S, ed. The wall paintings of Thera: Proceedings of the first international symposium. Athens: Thera Foundation, 2000:359–63.

American Botanical Council, 6200 Manor Rd, Austin, TX 78723

Ephedra and Caffeine’s Impact on Heart Rate and Systolic Blood Pressure

McBride B, Karapanos A, Krudysz A, et al. Electrocardiographic and hemodynamic effects of a multicomponent dietary supplement containing ephedra and caffeine JAMA. 2004;291(2):216-221.

Dietary weight-loss supplements often contain both ephedra and caffeine along with other natural ingredients. Anecdotal cases of sudden cardiac death and cerebrovascular adverse events associated with the combination of ephedra and caffeine have been reported. Consumers consider the herbal preparations as safe; however, safety data is lacking. Metabolife 356® (Metabolife International Inc, San Diego, CA) was one of the top selling dietary supplement containing ephedra and caffeine. It also contained a variety of ingredients, such as eleuthero (a.k.a. Siberian ginseng; Eleutherococcus senticosus), ginger (Zingiber officinale), and goldenseal (Hydrastis canadensis) in proprietary amounts.

An electrocardiogram (abbreviated as ECG or EKG) can be used to record the electrical activity of the heart during contraction. Waves (labeled as P, Q, R, S, T, and U) are generated on paper showing the activity of the atria and ventricles of the heart. The QT interval shows the excitation and relaxation of the ventricles. This study evaluated the impact of ephedra plus caffeine on the corrected QT (QTc) interval and on systolic blood pressure.

Fifteen healthy men and women participated in this randomized, double-blind, placebo-controlled, crossover study. Participants received either 1 capsule of Metabolife 356 or placebo. This was followed by a 7-day washout period after which they received the opposite treatment. Hemodynamic and electrocardiographic variables were evaluated immediately before and after ingestion of the capsules.

After dosing, the maximum QTc interval was 5.9% higher with Metabolife 356 than with placebo (P<0.001). The average QTc interval increased from baseline by 27.20 milliseconds when Metabolife 356 was consumed compared to 2.63 milliseconds when placebo was consumed (P=0.03). Fifty-three percent of the participants had QTc interval increases of at least 30 seconds while taking Metabolife 356. The QTc interval was greater in the Metabolife 356 group for every time point. The Metabolife group also had a higher post-dosing systolic blood pressure at 5 hours (P = 0.009). All patients receiving Metabolife 356 reported nonspecific adverse events, such as jitteriness, queasiness, or 'not feeling quite right.' No adverse events were reported while participants were taking placebo. One participant developed tachycardia (increased heart rate), one developed a hand tremor, and another developed premature ventricular complexes while taking Metabolife 356. The European Center for Proprietary Medicinal Products recognizes a drug induced increase in the QTc interval of at least 30 milliseconds as a potential cause of concern for developing ventricular tachycardia. Ventricular tachycardia is a potentially unstable rhythm that may result in fainting, low blood pressure, shock, or sudden death. The FDA has no official standards regarding products and ventricular tachycardia. However, the drugs cisapride and terfenadine were removed from the U.S. market due to cases of prolonged QTc intervals in the range of 13 to 17 milliseconds. Overall, this study showed that a single dose of a dietary supplement containing ephedra and caffeine significantly prolongs the QTc interval, which is a risk factor for developing heart arrhythmias (abnormal heart rhythm). The supplement also increased systolic blood pressure. The authors conclude that Metabolife 356 and other products with similar ingredients should be avoided until more information is known. —Heather S. Oliff, Ph.D American Botanical Council, 6200 Manor Rd, Austin, TX 78723

Consumption of Flavanol-Containing Cocoa Reverses Vascular Dysfunction in Diabetic Patients

Balzer J, Rassaf T, Heiss C, et al. Sustained benefits in vascular function through flavanol-containing cocoa in medicated diabetic patients: a double-masked, randomized, controlled trial. J Am Coll Cardiol. 2008;51(22): 2141-2149.

The prevalence of type 2 diabetes mellitus is increasing worldwide and is accompanied by an increasing risk of cardiovascular disease and mortality. Prescription medications are often used extensively in an attempt to prevent and/or treat complications of type 2 diabetes; however, they are often inadequate. Observational studies have shown that lifestyle modification (e.g., increased physical activity, weight loss, and dietary changes) can prevent diabetes and its associated complications. Epidemiologic studies have recently shown an inverse correlation between flavanol consumption and mortality from cardiovascular disease and the incidence of diabetes. Flavanols are predominantly found in fruit, vegetables, tea (Camellia sinensis), red wine (Vitis vinifera), and especially cocoa (Theobroma cacao). The results of dietary intervention trials have shown beneficial effects of flavanols on low-density-lipoprotein (LDL) oxidation, platelet aggregation, insulin sensitivity, endothelial function, and blood pressure. The objective of the present study was to investigate the feasibility and efficacy of a dietary intervention with flavanols from cocoa on improving vascular function in diabetic patients.

Men and women aged 50-80 years on hypoglycemic medication with a history of stably treated type 2 diabetes for at least 5 years were screened for eligibility. Ten patients were enrolled in a feasibility study, and 41 patients were enrolled in an efficacy study. Both studies had a randomized, double-masked design. In the feasibility study, the subjects consumed a single cocoa drink providing 75 mg (control), 371 mg (medium content), or 963 mg (high content) flavanols on 3 separate occasions (crossover design). Flow-mediated dilation (FMD), a measure of endothelial function, was measured an hour before and 1, 2, 3, 4, and 6 hours after ingestion of the cocoa drink. Blood samples were collected 2 hours after ingestion for the measurement of plasma flavanol concentrations. In the efficacy study, the subjects consumed 3 doses daily of either 321 mg flavanols (treatment group; 963 g/day total) or 25 mg of flavanols (control group; 75 mg/day total) for 30 days. FMD, blood pressure, heart rate, clinical variables, and plasma flavanol metabolites were measured at baseline and again on the same day 2 hours after ingestion of the day’s first amount of cocoa on days 0, 8, and 30. The cocoa drinks were prepared from a dry cocoa beverage mix (made using CocoaPro® cocoa powder; Mars Inc.; Hackettstown, New Jersey), and all of the cocoa drinks were similar in other macro- and micro-nutrient, caloric and alkaloid content, taste, and appearance. The primary outcome measure was endothelial function, which was determined on the basis of FMD of the brachial artery. Secondary outcome measures included changes in plasma flavanol metabolites 2 hours after ingestion of cocoa, blood pressure, and fasting plasma glucose, plasma lipid, and glycated hemoglobin concentrations.

In the feasibility study, the mean FMD of the study population was 3.8 ± 0.3%. A dose-dependent increase in FMD was observed after consumption of 371 and 963 mg flavanols, but not after ingestion of 75 mg flavanols (control). The highest FMD (5.5 ± 0.4%; P < 0.001 compared with baseline) occurred 2 hours after ingestion of the highest flavanol intake (963 mg). Plasma flavanols and FMD increased significantly in all of the subjects who ingested 963 mg flavanols. In the efficacy study, fasting FMD in the treatment group increased significantly from 3.3 ± 1.1% at baseline to 4.1 ± 1.1% on day 8 (P < 0.001) and to 4.3 ± 1.2% on day 30 (P < 0.0001). Significant acute-on-chronic increases (increases after consumption of the day's first amount) in FMD after flavanols ingested continued throughout the duration of the study (P < 0.0001). Plasma flavanol metabolites did not increase significantly in the control group but did increase significantly in the treatment group, from 1473.2 ± 670.9 nmol/L at baseline to 2177.7 ± 995.1 nmol/L (P = 0.0027) on day 30. No significant changes in blood pressure or in fasting plasma glucose and plasma lipid concentrations were observed in either the treatment or the control group on day 30, except for a significant decrease (P = 0.0063) in the LDL concentration in the treatment group. Glycated hemoglobin on day 30 was significantly lower than that at baseline in both the treatment (P = 0.0480) and control (P = 0.0038) groups. The authors conclude that their study "clearly establishes improvements of endothelial function after regular consumption of flavanol-containing cocoa in patients with type 2 diabetes." Flavanol consumption was well tolerated with no evidence of tachyphylaxia (desensitization to the treatment). The findings indicate the therapeutic potential of flavanols for helping reduce the risk of cardiovascular disease in type 2 diabetics on medication. —Brenda Milot, ELS American Botanical Council, 6200 Manor Rd, Austin, TX 78723

Vitamin D and intervention trials in prostate cancer: from theory to therapy.

Schwartz GG.

Departments of Cancer Biology and Epidemiology and Prevention, Wake Forest University School of Medicine, Winston-Salem, NC, USA. gschwart@wfubmc.edu

Studies of vitamin D and prostate cancer have advanced rapidly from the hypothesis that vitamin D deficiency increases the risk of prostate cancer to intervention trials of vitamin D administration in clinical cancer. The hormonal form of vitamin D, 1,25(OH)(2)D, exerts prodifferentiating, antiproliferative, anti-invasive, and antimetastatic effects on prostate cells. Moreover, normal prostate cells synthesize 1,25(OH)(2)D from serum levels of the prohormone, 25-hydroxyvitamin D. The autocrine synthesis of 1,25(OH)(2)D by prostatic cells provides a biochemical mechanism whereby vitamin D may prevent prostate cancer. Many prostate cancer cells have lost the ability to synthesize 1,25(OH)(2)D but still possess 1,25(OH)(2)D receptors. This suggests that whereas vitamin D (e.g., cholecalciferol) might prevent prostate cancer, existing prostate tumors likely would require treatment with 1,25(OH)(2)D and/or its analogs. The major obstacle to the use of 1,25(OH)(2)D in patients therapeutically is the risk of hypercalcemia. Several maneuvers to reduce this risk, including pulse dosing and the use of less calcemic 1,25(OH)(2)D analogs, have been explored in Phase I-III clinical trials. Once merely a promise, vitamin D-based therapies for prostate cancer may soon be medical practice.

PMID: 18619854 [PubMed – indexed for MEDLINE]

ABC Responds to Article on Herb-Drug Interactions in Journal of the American College of Cardiology

(Austin, TX) At least several times per year an article is published in a medical journal that purports to provide health professionals and the public with useful information on the safety of herbs and herbal dietary supplements. Instead, what sometimes occurs is an article written by people with apparently little to no expertise in the subject area of herbal medicine and medicinal plant research and likewise apparently peer reviewed—if peer reviewed at all—by reviewers with little botanical knowledge or expertise. Yesterday, the Journal of the American College of Cardiology published such an article.1

This particular article has so many flaws and errors that it is difficult to know where to begin to critically review it.

First, Latin names for the herbs discussed are missing, a disservice to any readers who may not be familiar with common names used in the United States.

Second, some of the tables in the article contain entries for “commonly used herbs,” which include the toxic plant oleander (Nerium oleander, a toxic herb with cardioactive glycosides not sold to consumers in the US dietary supplement market); chan su (presumably dried Chinese toad venom—not an herb nor generally available as a dietary supplement!); and uzara root (Xysmalobium undulatum), an anti-diarrhea herbal drug approved in Germany. None of these are “commonly” found in the US herbal dietary supplement market.

Grapefruit juice, which is well known for increasing serum levels of many pharmaceutical drugs, is referred to as an herb.

The authors refer to “ginseng” without clarifying which species of the genus Panax they are referring, many of which cause varying pharmacological effects. Also, with respect to “ginseng,” the authors unfortunately repeat the highly erroneous adverse effect information from the widely discredited 1979 uncontrolled study by RK Siegel on the “Ginseng Abuse Syndrome,” stating that “ginseng” can cause “hypertension, behavioral changes and diarrhea.”

Capsicum is listed in a table as being used for shingles, trigeminal, and diabetic neuralgia, when it is actually the US Food and Drug Administration-approved over-the-counter and prescription drug capsaicin, the vanillanoid compound derived from chili peppers (Capsicum spp.), which is used for such purposes.

There are more; the errors and problems in this paper are too numerous to list completely at this time.

While there are potential and actual interactions that various herbs can have with drugs used by patients with cardiovascular diseases, this paper will do little to improve professional awareness and skill in this area. However, the resulting media coverage will undoubtedly increase public confusion over what is an already confused subject. This paper should not have been published in its present form without serious additional edits, revisions, and deletions, and the Journal of the American College of Cardiology would be advised to retract it.

Reference

Tachjian A, Maria V, Jahangir A. Use of herbal products and potential interactions in patients with cardiovascular diseases. J Amer Coll Cardiol. 2010;55(6). [DOI:10.1016/j.jacc.2009.07.074].