IMM 32, 33, and 35: Introduction to Natural Health Products Flashcards
What is a natural health product (NHP)?
naturally occurring substances that are used to restore or maintain good health
- often made from plants, but can also be made from animals, microorganisms, and marine sources
What do natural health products include?
- herbal remedies (ie. echinacea, black cohosh)
- homeopathic medicines
- vitamins and minerals
- probiotics
- plant isolates (ie. soy isoflavones)
- essential fatty acids (e.g. omega-3)
- amino acids
- traditional medicines (ie. traditional Chinese medicine, Ayurvedic medicine)
What do natural health products exclude?
substances in:
- Schedule C (radiopharmaceuticals)
- Schedule D – biologics (but homeopathics and probiotics are NHPs)
- Tobacco Act
- Controlled Drugs Act Schedules I-V (ie. morphine)
- cannabis
What are the types of complementary and alternative medicines (CAMs)?
- natural products
- mind and body medicine
- whole medical systems
Complementary and Alternative Medicines (CAMs)
What are natural products?
dietary supplements
Complementary and Alternative Medicines (CAMs)
What are some examples of mind and body medicine?
- meditation
- yoga
- acupuncture (traditional Chinese medicine)
- hypnotherapy
- qi gong
Complementary and Alternative Medicines (CAMs)
What are whole medical systems?
embody beliefs, values, and assumptions that may differ from conventional medicine
- Ayurvedic medicine
- traditional Chinese medicine
- naturopathy
Describe the deep-rooted history of NHPs.
- ~35% of medicines originated from natural products (ie. many drugs derived from plants)
Are herbs drugs?
regulated as a subset of “drugs” at the level of the Food and Drugs Act
What is a drug?
substance that brings about a biological change in our body
- plants contain chemicals/constituents that can do this
Where can NHPs also be found?
- pharmaceuticals
- food
- cosmetics
How are NHPs regulated?
under the Natural and Non-prescription Health Products Directorate
- mission is to ensure that all Canadians have ready access to natural health products that are safe, effective, and of high quality, while respecting freedom of choice and philosophical and cultural diversity
Describe the regulatory compromise of NHPs.
- these regulations have implemented quality and safety standards for manufacturers, while significantly relaxing the standards for product efficacy claims
- if RCTs aren’t conducted, manufacturers can make claims based on “traditional uses” and other sources that are essentially anecdotal in nature
How do NHPs get regulated?
manufacturer must apply to the Health Product Directorate for a license
- must provide intended use and evidence of product safety and effectiveness for that use – can use pre-approved monographs (already approved for dosage forms, dose, uses and warnings) OR if departing from the monograph, must provide additional scientific evidence
- alternatively, if a product has a documented history of use beyond 50 years, than this traditional use can be an acceptable level of evidence of safety and effectiveness – so the claim a manufacture makes drives the evidence required
What are the two types of claims?
- modern
- traditional
What is a modern claim?
- sources of evidence: clinical studies, animal, and in vitro studies
- safety assessment: considers adverse effects from marketing data and seriousness of the condition
What is a traditional claim?
labelled as ‘traditionally used as…’
- sources of evidence: one reference from a pharmacopoeia OR 2 references from reputable sources (one may be expert opinion)
- used for 50 or more years
- safety assessment: must have 50 or more years of safe use
What happens once a product is approved?
- natural product number (NPN) on label
- if it is a homeopathic product, will have DIN-HM
- product is entered into the Licensed Natural Health Products Database
What are some possible amendments to the current regulations?
- propose to bring non-Rx drugs, NHPs, and cosmetics under one set of rules and regulate based on health risks (low, medium or high) – high will need to be based on scientific evidence, consumers will know that products making the same health claim were held to the same standard
- create consistent ‘post-market powers’
- improve product labeling to make information more clear and consistent with non-Rx drugs – want to reduce risk of harm to consumer
Describe people who use NHPs.
- rate health as good to excellent
- higher income range, university educated
Why do Canadians believe NHPs are safe?
- better than chemical products or drugs
- made from natural ingredients
- for sale
- free of side-effects and safer than a prescription
Why do people use NHPs?
- align better with their values and beliefs
- take them for prevention – to help maintain and promote health, to prevent illness and build immune system
- take them for treatment – to treat symptoms of a specific disease or illness, to treat a chronic condition for which there is no cure (offers some hope)
What are pharmacists professional obligation with respect to NHPs?
- detect and prevent NHP interactions (drugs/other NHPs/conditions)
- provide unbiased, evidence-based information to patients
- help patients make informed decisions
What does Health Canada say about NHPs?
regulated as a subset of drugs
What does the College of Pharmacists say about NHPs?
if you sell these products, you must be knowledgeable about them
Why is critical evaluation important?
- product claims can be general, misleading, and/or not backed by good scientific evidence
- sensational testimonials
- these products are readily accessible to patients, and you are often at ‘point of sale’ and can help patients navigate these claims
What is the framework for thinking critically about NHPs?
- assess issues/problems (NECESSARY) – NHP necessary/appropriate, expectations/knowledge of patient
- analyze – evidence for efficacy (NHP, other options), safety, adherence, benefits vs. risks
- advise and recommend NHP (if appropriate)
Many people seek treatment with NHPs for what chronic conditions?
- depression/anxiety
- dementia/memory loss
- osteoarthritis
- diabetes
- hypertension
Why is it good to ask patients about what they heard about an NHP and what their expectations are?
will help uncover beliefs, expectations, and misinformation, creating an opportunity for you to provide them with accurate evidence
What does NatMed have to say about the effectiveness of ginkgo for age-related cognitive decline?
possibly ineffective
What are the research challenges that come with studying the effectiveness of botanicals?
- variations between botanicals
- pooling of data
- small sample sizes
- difficulty with blinding
- inadequate financial resources of NHP manufacturers (compared to big pharma)
- cannot patent a plant – only a dosage form
Research Challenges
Variations Between Botanicals
- part of plant used (leaf, flower, root, rhizome) – huge biochemical variability
- time of harvest/growing conditions
- active constituent levels
- type of extraction solvent used (aqueous, alcoholic, glycerin)
- delivery form (solid, extract, raw herb, tea, etc.)
Research Challenges
Pooling of Data
example: effect of garlic on blood pressure
- conclusion: meta-analysis suggests that garlic preparations are superior to placebo in reducing blood pressure in individuals with hypertension
- 3 different forms of garlic
Research Challenges
Small Sample Sizes
many clinical trials are too small (or underpowered), reducing the chance of finding a true treatment effect
- ineffective vs. lack of statistical power
- is absence of evidence = evidence of absence
Research Challenges
Difficulty with Blinding
due to the distinct ‘odour’ of some herbal
preparations, patients in a clinical study may
be able to tell if they are getting treatment or
placebo
- did investigators say the products were indistinguishable
- ie. pungent herbs: valerian and garlic
What does the NHP label tell you? (4)
- latin name of herb (genus and species)
- dosage form
- what the product is standardized to
- strength (potency) of the product, which can be represented in different ways
What are some liquid dosage forms of NHPs? (3)
- plant juices
- extracts
- tinctures
What are some solid (tablets, capsule) dosage forms of NHPs? (2)
- raw powdered herb
- powdered extract
What are plant juices?
freshly harvested plants are pressed to release their juice
What is the advantage of plant juices?
‘entire’ part of plant used with nothing ‘left behind’
What are liquid extracts?
concentrated preparations
- solvents used to make the extracts are usually 30-70% ethanol in water mixture
- extraction solvent is chosen for its chemical properties, as it will selectively extract components in the plant that match those chemical properties
- expressed as a ratio of herbal material to the extraction solvent (ie. 50 parts plant to 1 part solvent)
- provides concentration of the final product
- more concentrated than tinctures
What are liquid tincture?
less concentrated than extracts
- ratio is usually ‘flipped’ (ie. 1 part plant to 12 parts solvent)
What are crude herbs?
can be air-dried, freeze-dried, or ground and used to fill gelatin capsules or compressed into tablets
What is the advantage of crude herbs?
minimally processed
What is the disadvantage of crude herbs?
limit to the amount of dry herb that can fit into a capsule
What are solid extracts?
prepared the same as a liquid extract, with the resultant liquid evaporated by various methods resulting in a concentrated solid
- start with 20 g dried herb
- constituents extracted by solvent
- 20:1 liquid extract
- evaporate resultant liquid
- 20:1 ratio of concentrated solid extract (20 g in 1 g)
Are most extracts standardized?
yes
What is standardization?
a process the manufacturers use to ensure batch-to-batch consistency
- products contain a minimum level or a range of one or more of biochemical constituent(s) or marker compound(s)
- achieved by characterizing and quantifying one or more biomarkers of pharmacological or unknown pharmacological activity
- helps to ensure quality and potency
- final mass has the same amount of biomarker every time
What are standardized extract ratios?
used to describe:
- strength of the extract
- amount of dried herb concentrated into the finished liquid extract (or solids for a solid extract)
How are most botanicals sold?
as solid extracts
How can doses on products be expressed as?
- raw equivalent weight of herb (pr dry herb equivalent)
- amount of extract used – small number compared to amount of dry herb equivalent (DHE)
How do we analyze evidence for safety (potential causes for harm) of NHPs? (4)
- lack of quality (purity and potency)
- inappropriate use
- allergic reactions
- NHP interactions
Lack of Quality (Purity)
What is adulteration?
fraudulent practices in which an herbal product is substituted partially or fully with impure, extraneous, improper or inferior products/substances
- ie. prescription medicines (biggest concern)
- ie. erectile dysfunction (sildenafil, tadalafil, vardenafil, or drug analogues)
- ie. sleep problems – benzodiazepines
- ie. inflammatory conditions – corticosteroids
Lack of Quality (Purity)
What is contamination?
accidental inclusion of impurities of a chemical or microbiological nature, or a foreign matter into or onto a starting material in the production process
- ie. microorganisms, heavy metals (problematic with ‘traditional’ herbs), pesticides, wrong plant (weed), wrong plant part
Lack of Quality (Potency)
amount of biomarker compound* that the product is supposed to be standardized to (ie. label claim) does not equal the same amount when tested for quality
- *compound that is characteristic to the NHP – can be either the active or inactive biochemical
Inappropriate Use
- misperception of safety – increased dosage/duration of therapy and over use (‘more is better’ mentality)
- delay in access to timely medical advice and more effective therapy – CAM has been associated with a 2-fold higher risk of death due to refusal of further treatment
- self-diagnosis of a serious or chronic medical condition (ie. depression, dementia)
Allergic Reactions
- 229 potential herbs/supplements able to cause dermatitis – ie. tea tree oil, feverfew, arnica
- echinacea – allergy to ragweed, daisies
- elderberry – allergy to grass pollens
NHP Interactions
NHP-Drug Interaction
- 33% of population take a NHP daily
- ~33% of Canadians use 3 or more NHPs concurrently
- 69% of NHP users are 55 years or older (ie. multiple prescriptions)
- 45% take Rx products and NHPs together
- patients taking NHP and Rx drugs were 6.4 x more likely to experience an adverse effect
NHP Interactions
What are the two types of NHP-drug interactions?
(best predicted by knowing the MOA of the NHP)
- pharmacokinetic
- pharmacodynamic
NHP Interactions
What are pharmacokinetic interactions?
altering ADME
- involve P450 system/p-glycoprotein
NHP Interactions
What are pharmacodynamic interactions?
can be synergistic or antagonistic
NHP Interactions
What are some examples of synergistic pharmacodynamic interactions?
- valerian & barbiturates
- gymnema & insulin
- St. John’s Wort & SSRIs
- fish oils & statins
- diuretic herbs (dandelion, yarrow, etc.) & diuretics
- chromium & anti-diabetic medication
NHP Interactions
What are some examples of antagonistic pharmacodynamic interactions?
- Korean ginseng and anti-hypertensives & lorazepam
- green tea & sedatives
NHP Interactions
NHP-NHP Interaction
herbs with the following properties:
- sedatives (German chamomile + valerian)
- anti-coagulant properties (ginkgo & ginger)
- hypoglycemic agents (chromium + Panax ginseng)
- phytoestrogens (red clover + soy)
NHP Interactions
NHP-Condition Interaction
- ginseng + diabetes – ginseng & white mulberry may reduce blood glucose levels
- SJW + bipolar depression – may induce hypomania
What should we consider for adherence to NHPs?
- cost
- many products have frequent dosing – if possible, look for greater potency
- many products will take at least a month to see any benefit
What therapies may be recommended?
evidence supports safety for the patient
AND
evidence supports efficacy equal to or better than alternatives
What therapies may be accepted?
evidence supports safety for the patient
BUT
evidence for efficacy is inconclusive
What therapies should be discouraged?
evidence indicates serious risk for the patient
OR
evidence indicates inefficacy
When is therapy acceptable?
- safe to take in that patient
- indicated for use
- evidence is positive
- self limiting condition
- chronic condition BUT mild-moderate signs and symptoms
- NOT DELAYING ACCESS to a better alternative
What is homeopathy according to Health Canada?
holistic, health philosophy and practice
What is homeopathy according to British Homeopathic Association?
gentle and non-invasive system of medicine that assists your body’s natural ability to restore itself to health
Why is homeopathy fundamentally incompatible with the current scientific understanding of the medicine, biochemistry, and even the basic physics that form the foundation of a pharmacist’s knowledge about medicines?
there is no medicinal benefit to homeopathy
- yet despite the obvious ethical issues of selling sugar pills to patients who may be led to believe these products may be beneficial, the profession of pharmacy hasn’t acted, or even seriously asked itself if selling these products is appropriate
What are the basic principles of homeopathy? (3)
- law of similars
- law of infinitesimals
- law of single remedy
Principles of Homeopathy
What is the Law of Similars?
substance that causes a specific symptom or set of symptoms in a healthy person can cure the same symptoms in a sick person
- this is the basic tenant of homeopathy
- like cures like
Principles of Homeopathy
What is the Law of Similars based on?
‘provings’
- done by gradually increasing a dose of a substance (plant, animal, mineral) in a healthy individual and monitoring their reactions/symptoms (physical, mental, and emotional)
Principles of Homeopathy
What is the Law of Infinitesmals?
remedies increase in biological activity as they are serially diluted (with agitation/shaking between each dilution)
- the smaller the dose, the more potent the remedy
- agitation (or succussion) of each dilution results in its ‘potentization’ through extraction of its ‘vital’ or ‘spirit-like’ nature
What is Arnica Montana?
used for trauma
- when a healthy person takes large doses of arnica, its toxic effects cause bleeding, bruising, swelling etc.
- when injured, taking the remedy in ultra-dilute quantities helps to minimize bruising, bleeding, swelling etc.
Principles of Homeopathy
What is the Law of Single Remedy?
there is ONE and only ONE remedy that will cure a patient:
- one remedy that in provings produces the most similar symptoms to those present in the patient
- only one that has the necessary sensitivity to ‘resonate’ with the disorder and bring about a cure
How does a homeopath diagnose?
- looks at the ‘symptom picture’ presented by the patient – physical, emotional, and mental symptoms, extensive interview process
- matches these symptoms to the product(s) that induce these symptoms in a health person
How are homeopathic remedies prepared?
- begins with mother tincture (base)
- original substance (ie. Arnica montana) is macerated in 99 parts of an alcohol/water mixture for a set period of time
- if NOT soluble, it is triturated with 99 parts of lactose for a period of time, then diluted with lactose until the final mixture is soluble in hydroalcoholic solution
- can be made from a plant, animal, or mineral
Dilution Ratio, Decimal Series, Centesimal Series
–
How dilute is dilute?
- 30X: serial 1 in 10 dilution of original substance 30 times (or 10^30)
- equal to one drop in a container 50 times the size of the earth
- after a 10^30 dilution, you would need to take approximately 2 billion pills to get 1 molecule of original substance
What are the available dosage forms of homeopathy?
- powder
- granule
- pellet/globule
- tablet
- solution
- ointment/cream/lotion/gel
- syrup
- suppositories
What does the homeopathic literature say about how homeopathy works?
- belief that the body’s own healing system can be stimulated energetically by ultra-dilute substances that can help return the system to balance
- memory of water theory: vigorous shaking (succussions) results in imprinting the ‘memory’ or signature of the original material onto the water molecules
Avogradro’s Number
dilutions beyond Avogadro’s number (6.023 x 10^23) or 24X or 12C potencies, makes it unlikely that even ONE molecule of the original substance remains in the finished product
What are the 4 types of homeopathy?
- classical (individualized)
- clinical (non-individualized)
- complex (non-individualized)
- isopathy (non-individualized)
What is classical homeopathy?
doctrine based on strict Hahnemannian principles – individualized therapy
- detailed history
- single remedy used based on current illness and ‘total symptom picture’
What is clinical homeopathy?
the same remedy that causes a condition is used to treat the symptoms of the person with that condition – non-individualized therapy
- formulated for the general population
- many ‘self-medication’ products (ie. oscillococcinum for the flu, chamomile for teething, arnica for bumps and bruises)
What is complex homeopathy?
similar to clinical with more than one remedy used in a fixed combination – non-individualized therapy
- based on the principle that one of the medications included is likely to be effective
- widely used for self-medication
What is isopathy homeopathy?
made by diluting and succussing suspected ‘causes of disease’ (ie. viruses, toxins, pollutants)
- unlike a vaccine, isopathic medicines contain miniscule amounts of a live virus
- one form is called a nosode (‘from disease’) which is prepared from a pathological specimen (ie. saliva, pus, urine, diseased tissue) – have been promoted and used as an alternative to vaccines
Homeopathic nosode products will include what statements to make it clear that they are neither vaccines nor alternatives to vaccines?
- this product is neither a vaccine nor an alternative to vaccination
- this product has not been proven to prevent infection – Health Canada does not recommend its use in children and advises that your child receive all routine vaccinations
Evidence for Efficacy of Homeopathy
- studies have been done on a wide variety of specific medical conditions
- the better quality trials were unable to show that homeopathy was effective in any of these conditions
- adverse effects of cancer treatment, soft tissue injury, induction of labour, ADHD, influenza, headache, asthma, IBS, dementia
Individualized Homeopathy vs. Placebo
small, statistically significant effect of individually prescribed homeopathic medicines but low quality evidence prevents a firm conclusion
Non-Individualized Homeopathy vs. Placebo
too few high quality trials – condition-specific analyses not credible
What is oscillococcinum?
used to treat and prevent influenza
- there is insufficient good evidence to enable robust conclusions to be made in the prevention or treatment of influenza
What are the direct risks of homeopathy?
- even the ‘toxic’ substances are highly dilute, so not likely to cause harm or interact with other medications
- lactose content – insufficient amounts for lactose intolerant people
What are the indirect risks of homeopathy?
- self diagnosis may delay proper diagnosis &
more effective treatment option - using them to treat serious conditions that may progress
What are some of the homeopathy regulations?
- all homeopathic medications sold in Canada must have a license and product # (DIN-HM)
- all medicinal ingredients must be listed in at least one of the US, French, German or European Pharmacopeias
- level of dilution (or concentration) allowed depends on the type of indication for use – whether specific or non-specific claim
- Ontario is the only province that regulates homeopaths
Why should pharmacists know about homeopathy?
- they are regulated as drugs
- to provide information and advice to patients about homeopathic principles and the LACK OF scientific evidence
- to identify patients who should NOT be self-medicating with homeopathic preparations
- to be able to distinguish between homeopathic and non-homeopathic products
Describe the dilution of homeopathic remedies.
- most remedies are ultra-dilute – with no plausible explanation as to how they might work
- high dilution remedies are safe and will not interact with medications
Is there evidence to support the use of homeopathy?
no – no evidence for the treatment of any particular condition
