Fabio Firenzuoli

Herbal Medicine Today: Clinical and Research Issues

Herbal medicine is the use of medicinal plants for prevention and treatment of diseases: it ranges from traditional and popular medicines of every country to the use of standardized and tritated herbal extracts. Generally cultural rootedness enduring and widespread use in a Traditional Medical System may indicate safety, but not efficacy of treatments, especially in herbal medicine where tradition is almost completely based on remedies containing active principles at very low and ultra low concentrations, or relying on magical-energetic principles. In the age of globalization and of the so-called ‘plate world’, assessing the ‘transferability’ of treatments between different cultures is not a relevant goal for clinical research, while are the assessment of efficacy and safety that should be based on the regular patterns of mainstream clinical medicine. The other black box of herbal-based treatments is the lack of definite and complete information about the composition of extracts. Herbal derived remedies need a powerful and deep assessment of their pharmacological qualities and safety that actually can be realized by new biologic technologies like pharmacogenomic, metabolomic and microarray methology. Because of the large and growing use of natural derived substances in all over the world, it is not wise to rely also on the tradition or supposed millenarian beliefs; explanatory and pragmatic studies are useful and should be considered complementary in the acquisition of reliable data both for health caregiver and patients.

Essential Oils Loaded in Nanosystems: A Developing Strategy for a Successful Therapeutic Approach

Essential oils are complex blends of a variety of volatile molecules such as terpenoids, phenol-derived aromatic components, and aliphatic components having a strong interest in pharmaceutical, sanitary, cosmetic, agricultural, and food industries. Since the middle ages, essential oils have been widely used for bactericidal, virucidal, fungicidal, antiparasitical, insecticidal, and other medicinal properties such as analgesic, sedative, anti-inflammatory, spasmolytic, and locally anaesthetic remedies. In this review their nanoencapsulation in drug delivery systems has been proposed for their capability of decreasing volatility, improving the stability, water solubility, and efficacy of essential oil-based formulations, by maintenance of therapeutic efficacy. Two categories of nanocarriers can be proposed: polymeric nanoparticulate formulations, extensively studied with significant improvement of the essential oil antimicrobial activity, and lipid carriers, including liposomes, solid lipid nanoparticles, nanostructured lipid particles, and nano- and microemulsions. Furthermore, molecular complexes such as cyclodextrin inclusion complexes also represent a valid strategy to increase water solubility and stability and bioavailability and decrease volatility of essential oils.

Ear acupuncture in European traditional medicine.

Auricular acupuncture is a diagnostic and treatment system based on normalizing the bodys dysfunction through stimulation of definite points on the ear. Rudimentary forms of acupuncture which probably arose during the Stone Age have survived in many parts of the world right down to present day. It was used in the ancient Egypt, Rome, Greece and all the Mediterranean area. It is a microacupuncture technique similar to reflexology, and was first described in France in 1950 by Paul Nogier who is considered the Father of modern ear acupuncture. It was speculated that the technique works because groups of pluripotent cells contain information from the whole organism and create regional organization centers representing different parts of the body. Nevertheless stimulation of a reflex point in the ear seems relieve symptoms of distant pathologies. Modern research is confirming the efficacy of ear acupuncture for analgesia and anxiety related disease, while tobacco dependence and other substance abuse still need confirmation. Actually main methodological problems with auricular acupuncture are that exist too many maps with little agreement regarding point location in the ear, and that the correspondence or reflex systems does not correlated with modern knowledge of anatomy and physiology.

Use, Attitudes and Knowledge of Complementary and Alternative Drugs (CADs) Among Pregnant Women: a Preliminary Survey in Tuscany.

To explore pregnant womens use, attitudes, knowledge and beliefs of complementary and alternative drugs (CADs) defined as products manufactured from herbs or with a natural origin. A preliminary survey was conducted among 172 pregnant women in their third trimester of pregnancy, consecutively recruited in two obstetrical settings; 15 women were randomly selected to compute a test-to-retest analysis. Response rate was 87.2%. Test-to-retest analysis showed a questionnaires reproducibility exceeding a K-value of 0.7 for all items. Mean age was 32.4 ± 0.4 years; most women were nulliparae (62.7%). The majority of subjects (68%) declared to have used one or more CADs during their lifetime; 48% of pregnant women reported taking at least one CAD previously and during the current pregnancy. Womens habitual use of CADs meant they were at higher risk of taking CADs also during pregnancy (adjusted odds ratio = 10.8; 95% confidence interval: 4.7–25.0). Moreover, 59.1% of the subjects were unable to correctly identify the type of CADs they were using. The majority of women resorted to gynecologists as the primary information source for CADs during pregnancy, while they mainly referred to herbalists when not pregnant. Habitual use of CADs seems to be a strong predictor for their ingestion also during pregnancy; in addition most subjects were unable to correctly identify the products they were taking. In the light of the scanty data concerning the safety of CADs during pregnancy, these preliminary results confirm the need to investigate thoroughly the situation of pregnant women and CADs consumption.

Surveillance of suspected adverse reactions to natural health products in Italy

Natural health products are promoted to the public as equally or more effective and less toxic than conventional drugs. However, some ‘natural’ medicines, and in particular some herbal medicines, are known to have adverse effects. The Italian Pharmacovigilance System, in charge of the Italian Medicines Agency, collects spontaneous reports only for registered drugs. The awareness of the need of surveillance of the safety of natural health products has stimulated the implementation of a suspected adverse reaction reporting system in Italy. The system has been set up by the Italian National Institute of Health.

Myopathies associated with red yeast rice and liquorice: spontaneous reports from the Italian Surveillance System of Natural Health Products

Many drugs can be responsible for muscle injuries. Besides statins, recognised as the drugs most commonly associated with severe myopathies, other medications such as neuroleptics, proton pump inhibitors and recently gabapentin [1] have been associated with this type of adverse drug reaction (ADR). Recent case reports have highlighted that active compounds from medicinal plants can also be responsible for myopathies [2, 3], including rhabdomyolysis but a systematic evaluation of reporting databases is still lacking. In the present study, the Italian ADR database [4, 5] of natural health products was analyzed with the aim of evaluating the possible ‘signal alarms’ due to herbal medicines and muscle injuries. A panel of experts, including a medical toxicologist, a pharmacist and a physician expert in herbal medicine reviewed all reports of myopathy to define the causality assessment using the Naranjo probability scale [6]. From April 2002 to December 2007, nine reports of muscle disorders were identified, of which seven were reported by phytotherapy specialists, one by a hospital physician, and one by a general practitioner. As shown in Table 1 most disorders (7/9) were due to red yeast rice (Monascus purpureus) (n = 4) and liquorice (n = 3) (Glycyrrhiza glabra). In all reports Monascus purpureus was used to treat hypercholesterolaemia, and all events were assessed as ‘probable’, according to the Naranjo probability scale; all cases showed increased concentrations of serum creatinine phosphokinase (CPK) and their onset varied from 2 to 6 months. One of the patients reported previous statin intolerance, while the one who showed the highest increase in CPK (401 IU l−1; normal range 24–195 IU l−1) reported concurrent muscle pain. In the latter case the ADR did not resolve after discontinuation of red yeast rice. Table 1 Reports of myopathies associated with use of herbal drugs A case of rhabdomyolysis was diagnosed after 3 months of liquorice consumption (30–40 g day−1) but signs and symptoms disappeared after dechallenge. Laboratory data were unavailable. Another patient presented with a remarkable increase in CPK (8000 IU l−1) and blood nitrogen (6.0 mg dl−1, normal range: 0.2–6.0 mg l−1) after 20 days of self-administration of a laxative product containing liquorice. At a 6-month follow up, CPK concentrations were still elevated. Causality was assessed as ‘possible’ since the patient had undergone a previous 8-year consumption of simvastatin and lansoprazole, two drugs possibly associated with muscle injury. Although both drugs were stopped several weeks before the onset of rhabdomyolysis, their previous consumption was taken into account when assessing the causality relationship. A case of hypertension, hypokalaemia, hypernatraemia and increased CPK was also reported after 3 months of liquorice juice consumption as self-medication for chronic hypotension. After dechallenge and anti-aldosterone treatment, the patient completely recovered. According to a WHO critical term list, all reports referring to liquorice consumption were classified as ‘serious’ due to hospital admission and two out of three reactions were assessed as ‘probable’. In two cases, symptoms completely resolved after product discontinuation. Major alternative causes of muscle disorders, including alcohol abuse, illicit drug use, infections, metabolic, endocrine or inflammatory diseases were excluded in all seven patients. We can confirm the recent ‘signal’ seen in the medical literature of case reports of muscle disorders associated with red yeast rice and liquorice through our analysis of the Italian national database of adverse reactions to natural health products. All reported cases of ADRs are biologically plausible and supported by preclinical and physiopathological rationale. For instance, chronic or acute liquorice use, through glycyrrhizic acid, is able to inhibit 11β-hydroxysteroid deydrogenase-2 impairing lipid metabolism in muscle cells [3], while Monascus purpureus contains mevalonic acid and Monacolin K, an agent that has the same structure and activity as lovastatin [2, 7]. Although some case reports [4, 8, 9] have already raised this concern, favourable attitudes towards herbal preparations are still strong in industrialized countries [10]. In the majority of the cases reported here, red yeast rice was used to treat dyslipidaemia, often as a self-medication, without a physicians and/or pharmacists supervision. Many patients could therefore be exposing themselves dangerously to the additive effect of herbal and synthetic drugs, such as statins, whose potential adverse effect on muscle is well documented. Moreover, a previous statin intolerance constitutes a critical point for red yeast rice use; this should be taken into account by physicians when suggesting this kind of natural remedy to their patients, as well as by statin-intolerant patients seeking natural alternatives to synthetic drugs, who might be unaware of the real benefit–harm profile of these products.

Suspected adverse reactions associated with herbal products used for weight loss: a case series reported to the Italian National Institute of Health

PurposeThe aim of this study was to describe suspected adverse reactions (ARs) associated with herbal products used for weight control in Italy.MethodsSpontaneous reports of suspected ARs associated with herbal products used for weight control were collected by the Italian National Institute of Health (April 2002 to June 2010), and the causality assessment was performed.ResultsForty-six of the suspected ARs were associated with herbal products used for weight control. Women were involved in 85% of the reports. The reactions affected mainly the cardiovascular system, the skin, the digestive system, the central nervous system, and the liver. A large proportion of ARs were serious. In more than half of the suspected ARs, the use of other therapies (herbs and/or drugs) was reported, while concomitant conditions were present in 22% of the reports.ConclusionsThe use of herbal dietary supplements for weight loss is associated with several ARs. Considering the risk/benefit ratio, consumers should pay attention when using these products.

Surveillance of Suspected Adverse Reactions to Natural Health Products: The Case of Propolis

Natural health products are promoted to the public as equally or more effective and less toxic than conventional drugs. However, some ‘natural’ medicines are known to have adverse effects.From April 2002 to August 2007, 18 suspected adverse reactions associated with propolis-containing products were reported to the national surveillance system of natural health products, coordinated by the Italian National Health Institute. Sixteen reports concerned allergic reactions (with dermatological or respiratory symptoms), while two concerned the digestive tract. Some of the reactions were serious: six patients were admitted to hospital or visited an emergency department and in two of these a life-threatening event was reported. In seven patients (four of whom were children), an allergic predisposition was indicated.Propolis, a resinous substance collected by honeybees from the buds of living plants, has been used for several purposes (dermatitis, laryngitis, oral ulcers) because of its wide range of suggested activities (antibacterial, antiviral, anti-fungal, anti-inflammatory, antioxidant and chemopreventive actions). However, propolis is also a potent sensitizer and should not be used in patients with an allergic predisposition, in particular an allergy to pollen.In Italy, products containing bee derivatives (bee pollen, royal jelly or propolis) are available to the public as food supplements. No label warning of possible adverse reactions is found on the packaging, although it is well known that atopic and asthmatic individuals may be at an increased risk of allergic reactions after using these products. The public and healthcare practitioners should be aware of the risk of allergic reactions to products derived from bees and a warning should be added to the packaging of these products.

Homeopathy and complementary medicine in Tuscany, Italy: integration in the public health system.

The healthcare programmes of the Region of Tuscany, Italy have contained references to various types of non-conventional medicine since 1996, and the last three Regional Health Plans have includes a chapter on non-conventional medicine that arguably represent the greatest degree of integration of such therapies in the public health care system achieved thus far in Italy. The Plan aims to guarantee definitive integration in the Regional Health Service of types of non-conventional medicine which are supported by a sufficient level of scientific evidence to allow them to be defined as forms of complementary medicine (acupuncture, herbal medicine, homeopathy and manual medicine). Moreover, in 2007 the Regional council of Tuscany, for the first time in Italy, approved a regional law disciplining the practice of complementary medicines on the part of doctors, dentists, Veterinarians and pharmacists.

Complex Traditional Chinese Medicine for Poststroke Motor Dysfunction A Systematic Review

Background and Purpose— For its current dimensions, stroke represents the world’s primary health challenge. In China stroke is the second most common cause of death. Traditional Chinese Medicine (TCM) has for many centuries been used, and it is still widely used today in countries of south and east Asia for the treatment of people with stroke. The objective of this systematic review was to evaluate whether complex Traditional Chinese Medicine (cTCM) improves poststroke motor recovery. In particular, we defined cTCM as intervention that included at least acupuncture and Chinese herbal medicine. Methods— An extensive search including PubMed, EMBASE, CBM, and the Cochrane Library was performed up to December 2007. Randomized clinical trials (RCTs) about cTCM for motor dysfunction of poststroke were searched irrespective of any language. The quality of each trial was assessed according to the Cochrane Reviewers’ Handbook 4.2.6. Results— After selection of 11 234 articles, 34 RCTs and quasi-RCTs were included. All these trials were conducted in China and published on Chinese journals. All trials but one reported results in favor of cTCM treatments suggesting a strong publication bias. Because of the significant clinical and methodological heterogeneity, no meta-analysis was performed and thus no cumulative result was obtained pooling data of RCTs. Conclusions— What appears from this systematic review is that scant data are available to evaluate efficacy of cTCM for poststroke motor dysfunction. Most of the primary studies available for this review were inadequately designed trials characterized by unknown dropout rates and definitional vagueness in outcomes measures. None of the studies approached important end points like death, survival times, rate of dependency, reduction in length of stay in hospital, etc. The key to lead to evidence-based practices is establishing a consensus on standardized relevant outcome measures and then designing and conducting appropriate RCTs that adopt those standards.