EXPLOSIVE GROWTH OF HERBAL MEDICINES

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Viewed as a balanced and moderate approach to healing, herbal medicines have grown exponentially. This popularity is attributed to a preference for natural therapies and a greater interest in alternative medicines. Traditional medicinal practice involving herbs is an integral part of many communities, and the World Health Organization (WHO) estimates that 80% of the world’s population relies on herbal medicine as a primary source of healthcare. Strategic marketing by manufacturers of herbal medicines has expanded product visibility, and the continuous introduction of new herbal products into the market has led to public health issues and safety concerns.

CHALLENGES
All medicines must be safe and of suitable quality, yet a single herb plant may contain hundreds of natural constituents. Such complexity means that the control of raw herbal materials and finished herbal products is more involved than for conventional pharmaceuticals. A substantial proportion of the global drug market, herbal medicines require pharmacovigilance and safety monitoring. The WHO recommends national quality specifications and standards related to the manufacturing, import, and marketing of herbal materials; however, in most countries, herbal medicines arrive on the market without mandatory safety or toxicological evaluations and without evidence of quality and efficacy. The common misconception that natural products are nontoxic and devoid of adverse effects leads to improper use and unrestrained intake, along with the risk of severe poisoning and acute health problems. Herbal medicinal products have been implicated in cases of poisoning, with certain compounds capable of reacting with cellular macromolecules including DNA and inducing cellular toxicity and/or genotoxicity. 

SAFETY AND TOXICITY
The safety of traditional and herbal medicines is paramount to national health authorities and the general public, yet:

• There is limited knowledge of potential adverse reactions.
• Many herbal preparations remain untested and their use unmonitored.
• The safest and most effective therapies have not been identified, and rational use has not been promoted.
• Traditional health practitioners may not be certified or licensed.

Possible causes of adverse events resulting from the consumption of herbal medicines include
mistaken use of the wrong plant species, misidentification of medicinal plants, adulteration of herbal products with undeclared medicines, mislabeling of herbal medicinal products, contamination with toxic or hazardous substances, overdose, and misuse of herbal medicines by healthcare providers or consumers – including concomitant administration with other medicines. Predictably, adverse event analysis with herbal medicines is more complex than with conventional pharmaceuticals.

Evaluation of product safety is further complicated by geographical origin of the plant material, processing technique, route of administration, and compatibility with other medicines.

PROPERTIES OF SPECIFIC HERBS    

Aristolochic acids and Aristolochia species. After findings of potential nephrotoxicity and carcinogenicity of aristolochic acids, studies confirmed their genotoxic activity. Aristolochic acid-related DNA adducts have been found in the renal tissues of patients; these mutagenic adducts are usually poorly repaired and capable of persisting for years in DNA. All plants in the genus Aristolochia contain aristolochic acids and are banned in Europe and the United States. Intake of slimming pills containing the Chinese herb Aristolochia fangchi has been linked to Aristolochic acid nephropathy and the development of subacute interstitial fibrosis of the kidneys and urothelial malignancies.
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The tubers and roots of the Aconitum species have been used medicinally for centuries in herbal preparations for stroke, heart failure, diabetes, rheumatic fever, painful joints, gastroenteritis, edema, bronchial asthma, and other disorders. Aconitum carmichaeli and Aconitum kusnezoffii are used traditionally for pain relief.  The toxicity of these plants derives primarily from the presence of diester diterpene alkaloids. Severe cases of cardiotoxicity from consumption of aconitine-containing herbal preparations manifest as ventricular tachycardia and fibrillation and eventually death. Bradycardia and hypotension have also been observed. The toxicity of aconitine and related diterpene alkaloids can be denatured by special processing and in China only the processed (i.e., detoxified) tubers and roots of Aconitum can be administered orally. More than 70 techniques are applied to the processing of Aconitum roots in order to reduce levels of toxic alkaloids below a certain threshold; note that this principle is not accepted in Europe. 

​Traditionally, Tussilago farfara or coltsfoot has been used for thousands of years to treat pulmonary complaints, acute and chronic coughs, bronchitis, laryngitis, and asthma. The polysaccharides are anti-inflammatory and immuno-stimulating, as well as demulcent, and the flavonoids have anti-inflammatory and antispasmodic actions. Tussilago farfara is generally regarded as nontoxic, although total alkaloids isolated from this plant have demonstrated hepatotoxicity. Recently, the effects of the pyrrolizidine alkaloids found in Tussilago farfara were reviewed and hepatic veno-occlusive disease and cirrhosis suggested as potential disease outcomes in humans. Restricted intake of pyrrolizidine-containing herbs is recommended.

There are reports on the efficacy of Garlic (Allium sativum) for management of hypertension and hypercholesterolemia. The main compound in the fresh plant is alliin, which on crushing undergoes enzymatic hydrolysis by alliinase to produce allicin. Due to the antiplatelet effects of garlic, care should be taken if given in combination with antiplatelet drugs and warfarin. Adverse effects associated with garlic extract include burning sensation in the gastrointestinal tract, nausea, diaphoresis, and lightheadedness. 

The active compounds of St. John’s wort (Hypericum perforatum) include hypericin, hyperforin, and melatonin. The plant has clinically well-established effects for mild depressive symptoms, although allergic reactions, headache, dizziness, restlessness, fatigue, gastrointestinal symptoms, and photosensitivity have been reported, as well as hyperesthesia and a syndrome of dyspnea and hyperventilation with mydriasis, nausea, palpitations, and tremors. Interaction of St. John’s wort with antidepressants and anticoagulants has been demonstrated and use is not recommended in pregnancy because of the herb’s uterotonic activity.

RECOMMENDATIONS
It is vital to inform and protect the public by identifying risks associated with herbal medicines, incorporating herbal products into pharmacovigilance systems, linking safety monitoring to the regulatory status of herbal medicines, promoting safe use through adequate labeling and appropriate patient information, advancing knowledge of traditional, complementary, alternative, and herbal medicines within national drug regulatory authorities, and standardizing definitions and categorizations of herbal medicinal plants on an international level. Herbal medicines must be assessed for safety, toxicity, efficacy, and quality.

Providers of medicines – physicians, nurses, and pharmacists – need training to understand how herbal medicines affect the health of their patients. Healthcare professionals and medical communicators (translators and writers) must inform the public. The right knowledge base is crucial. 

Citation: Ekor M (2014) The growing use of herbal medicines: issues relating to
adverse reactions and challenges in monitoring safety. Front. Pharmacol. 4:177. doi:
10.3389/fphar.2013.00177

​Conclusions
In the Annals of Internal Medicine study, Cucurma longa (turmeric) extract was more effective than placebo for knee pain but did not affect knee effusion–synovitis or cartilage composition. In the Chinese Journal of Tissue Engineering Research article, common femoral vein index (the primary observation indicator) in the tuina group was lower than in the control group, demonstrating that lower limb point pressure therapy at the Shu transporting points was able to reduce common femoral vein stasis after total knee arthroplasty, improving blood flow in the lower limbs after knee replacement and reducing the risk of thrombus formation. Other indicators, such as D-dimer value and pressure pain threshold, were also improved in the tuina group relative to the control group.

BEHAVIORAL CARDIOLOGY  
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In medical treatment today, heart health requires more than blood pressure control or the right pharmacologic therapy. Doctors advise lifestyle modifications in the form of diet and exercise yet may encounter resistance. Patients must be willing to comply with lifestyle modifications and often such motivation is tied to their psychological health. If a patient already has underlying depression, then news of serious cardiovascular disease may deepen such depression and dampen motivation.
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Behavioral cardiology looks at the links between behavioral and psychosocial factors and the origin and progression of coronary heart disease. Randal Thomas notes in Behavioral Cardiology: Where the Heart and Head Meet (U.S. Cardiology Review, 2006) “Results of recent clinical research have strengthened the understanding and management of the links between psychological health and heart health, and have moved the field of behavioral cardiology steadily closer into the mainstream of current clinical cardiology.” Thomas notes the importance of behavioral cardiology: Adverse psychosocial factors are common in persons with coronary artery disease and up to 50% of survivors of myocardial infarction present with significant anxiety and/or depressive disorders. These adverse psychosocial factors can significantly worsen coronary artery disease risk and prognosis. Moreover, psychosocial health status is generally responsive to behavioral and pharmacologic therapies.

CARDIOLOGISTS ALERT TO PSYCHOLOGICAL AND CARDIOVASCULAR FACTORS
Physical and emotional factors contribute to feelings of overwhelming depression and hopelessness in a vulnerable patient who has recently experienced a heart attack. This presents an unusual dilemma in current cardiovascular healthcare. The cardiologist must treat the underlying disease and the risk of heart disease and at the same time be aware of related psychosocial factors, such as hostility and anxiety. Treatments that effectively treat both psychosocial and coronary artery disease outcomes can be elusive.

The cardiologist is often the first to see a patient during and after cardiovascular events at a time when adverse psychosocial factors may become more visible and patients are more open to therapeutic recommendations. The cardiologist's challenge is to identify ​coexisting heart disease and psychological distress, and then successfully intervene and initiate the early steps of  psychosocial care.  ​

PSYCHOSOCIAL FACTORS THAT INCREASE THE RISK OF HEART DISEASE
As important as smoking, high blood pressure, obesity, and cholesterol, psychological factors may be the final insult resulting in a heart attack or stroke. Psychological factors contribute to atherosclerosis, the slow, corrosive process that damages artery walls. Depression, stress, loneliness, pessimistic outlook, and other psychosocial factors influence heart health. Conversely, heart disease affects the brain and the mind.

DEPRESSION
Symptoms of depression, as well as full-blown major depression, contribute to heart disease. The prognosis is worse for people who become depressed after a heart attack or stroke, heart surgery, or the onset of heart failure.

ANGER AND HOSTILITY
​Atherosclerosis seems to advance faster in people who score high on anger or hostility scales. Anger may even initiate heart attacks. In the Harvard-based Determinants of Myocardial Infarction Onset Study, one in every 40 heart attack survivors reported an "episode of anger" in the two hours before the attack.

ANXIETY
Intense anxiety associated with fear of enclosed places, heights, and crowds may set off a sudden cardiac arrest. These often-fatal heart attacks happen when the heartbeat abruptly turns fast and uncoordinated.

LACK OF SOCIAL SUPPORT
Among heart attack survivors, social isolation is almost as important as high cholesterol, high blood pressure, and smoking in the prediction of long-term survival.

CHRONIC STRESS
Constant stress from work, financial problems, a troubled marriage, taking care of sick family members, or even living in an unsafe neighborhood have been linked to the development of heart disease and poor prognosis.

SUDDEN EMOTIONAL STRESS
Sudden emotional turmoil can trigger a temporary but serious heart condition also known as  broken heart syndrome or stress cardiomyopathy, in which stress hormones stun the cells of the heart. Researchers have documented broken heart syndrome after a death in the family, a divorce, a surprise (even a good surprise), a robbery, a car accident, or other physically draining event.

HEALTHY BEHAVIOR IS GROUNDED IN EMOTIONAL STATE 
Healthcare providers agree that our health behaviors are grounded in the larger context of our emotions, moods, and even parts of our personality. Stress, loneliness, depression, and anxiety all exact a toll. Dr. Alan Rozanski divides the behavioral risk factors for coronary heart disease into physical health behaviors, negative emotions and negative mental mindsets, chronic stress, social isolation and poor social support, and lack of sense of purpose. "Negative psychosocial factors promote illness by fostering negative health behaviors and by their direct pathophysiological effects," he says. "These effects can vary according to the type of psychosocial stress, but as a group they include induction of autonomic dysfunction, heightened cardiovascular reactivity, insulin resistances, central obesity, increased risk for hypertension, endothelial and platelet dysfunction, and unfavorable alterations in brain plasticity and cognitive function.”

POSITIVE AND NEGATIVE FEEDBACK LOOPS OFFER TREATMENT OPPORTUNITY
Psychosocial factors form part of positive and negative feedback loops, which offer opportunities for overall approaches to treatment. Transforming one component of the negative feedback loop may create a positive feedback loop. For example, treating depression can improve health behaviors, reduce stress, improve social performance, and increase sense of purpose. Exercise reduces heart rate, blood pressure, and cortisol and glucose responses to psychosocial stress, and it buffers the relationship between depression and inflammation.   

​LIFESTYLE MODIFICATIONS FOR HEART HEALTH
​Primary prevention measures and lifestyle interventions offer hope for the heart patient.
They include:
Healthy and balanced diet
Reduced salt intake, increased potassium intake
Weight loss
Smoking cessation
Appropriate exercise (moderate intensity, such as a 30-minute daily walk)
Stress reduction
Lipid regulation
Aspirin
Behavioral interventions including talk therapy, antidepressant therapy, and mindfulness practices
 
Behavioral interventions such as talk therapy, antidepressant therapy, and mindfulness practices relieve mental stress and maintain emotional balance. Treating heart disease by treating mood and emotion holds promise. Lifestyle interventions offer both physical and emotional benefits, and success with one modification may improve the patient's outlook in other areas.

Habits good for the heart seem to be good for the mind and brain as well. Ask anyone who exercises regularly about the mental benefits of exercise!

​MEMORIAL SLOAN KETTERING CANCER CENTER
​​https://www.mskcc.org/cancer-care/diagnosis-treatment/symptom-management/integrative-medicine​

MAYO CLINIC
https://www.mayoclinic.org/tests-procedures/complementary-alternative-medicine/about/pac-20393581​

NATIONAL CENTER FOR COMPLEMENTARY AND INTEGRATIVE HEALTH (NCCIH)
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A SAMPLING OF NCCIH TOPICS: ​ 

• La gripe y los resfriados: en detalles
• Dietary supplements and diabetes management
• Herbal supplements and cholesterol
• Cuidado con los "suplementos dietéticos" fraudulentos
• Mind and body approaches for chronic pain
• Hepatitis C and dietary supplements
• La espiritualidad en el tratamiento del cáncer
• Mind and body approaches for cancer symptoms and treatment side effects
• Dietary supplement safety alerts

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