Part iii abs: traditional, complementary & alternative medicine

LESSON 1: TRADITIONAL, COMPLEMENTARY & ALTERNATIVE MEDICINE

Defining and a*tudes to TCAM

Defini'ons:
• Tradi'onal vs modern
• Conven'onal vs alterna've
• Western vs Eastern
• Science vs pseudoscience
A;tudes:
• “Quackery” & pseudoscience
• Medicine works – if it doesn’t work it’s not medicine
• Alterna've implies there is an effec've alterna've to science-based medicine
• Complementary implies it increases the effec'veness of science-based medicine
Kate Cha5ield (2018), Tradi?onal and complementary Medicines: Are they ethical for Humans, Animals and the Environment,
Springer Interna?onal Publishing:
• “On the one hand we appear to have a shared understanding of what they all mean and, on the other, no defining quality
that applies to all types.” (p. 6)

Comparison of T&CM and conven?onal medical approaches:

Tradi'onal and complementary medicine Conven'onal medicine

Takes a holis'c approach to diagnosis and Takes a reduc'onist approach to diagnosis and treatment; i.e. various
treatment; i.e. physical, mental, spiritual, and specialists are concerned with individual illnesses (Milgrom 2006)
environmental factors are considered (BarreU et
al. 2003)
Commonly invokes an underlying vitalis'ca Based upon a biomedical understanding of the body (Colquhoun and Isbell
doctrine (Bellavite 2003) 2007)
Treatment is tailored to the individual (Franzel et Treatments are largely based upon what works for the 'average person
al. 2013) (Cronje and Fullan
2003)
Treatments are derived from, and in tune with, Treatments can be highly medicalised (Hughes
nature (Ostendorf 1991) 2008)
Cure is encouraged from within; there is high Cure is interven'onist in approach; symptoms are controlled (di Sarsina et
regard for self-healing (Fulder 1988) al. 2012)
Commonly used to promote and maintain health, Most commonly used in a reac've manner for trea'ng exis'ng complaints
for preventa've purposes (Patriani (Teixeira 2009)
Justo and dé Andrea Gomes 2008)
High regard for autonomy: pa'ent is ac've Ohen cri'cised for taking a paternalis'c approach; doctors are the experts
partner in the healing process (Sharma 1992) (White 2000)

Professional Ethics
• These therapies are widely available and increasingly used.
• You may be asked for advice.
• You may have to treat people who are using them.
• You may be obliged to sell them.
• You may choose to prac'ce one.
• How much should your personal beliefs influence your professional behaviour?

Cri?cisms
• Use of endangered species.
• Safety Concerns.
o The WHO notes that "inappropriate use of tradi'onal medicines or prac'ces can have nega've or dangerous
effects" and that "further research is needed to ascertain the efficacy and safety" of such prac'ces and medicinal

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 plants used by tradi'onal medicine systems. As a result, the WHO has implemented a nine-year strategy to
"support Member States in developing proac've policies and implemen'ng ac'on plans that will strengthen the
role tradi'onal medicine plays in keeping popula'ons healthy."

The placebo effect

• The placebo effect is when a person's physical or mental health appears to improve aher taking a placebo or 'dummy'
treatment.
• Science has shown that placebos:
o Work best on symptoms modulated by the brain, such as pain management, stress-related insomnia, cancer
treatment side effects like fa'gue and nausea.
o Involve a complex neurobiological reac'on that includes increases in feel-good neurotransmiUers, like
endorphins and dopamine, as well as greater ac'vity in certain brain regions linked to moods, emo'onal
reac'ons, and self-awareness.
o Need the ritual of treatment, condi'oning, and expecta'on.

WHO tradi?onal medicine strategy

T&CM is an important and ohen underes'mated part of health care, found in almost every country in the world, with increasing
demand for its services. TM, of proven quality, safety, and efficacy, contributes to the goal of ensuring that all people have access
to care. Many countries now recognize the need to develop a cohesive and integra've approach to health care hat allows
governments, health care prac''oners and, most importantly, those who use health care services, to access T&CM in a safe,
respecpul, cost-efficient and effec've manner. A global strategy to foster its appropriate integra'on, regula'on and supervisión
will be useful to countries wishing to develop a proac've policy towards this important - and ohen vibrant and expanding - part of
health care..

Three strategic sectors:

1. Build the knowledge base that will allow T&CM to be managed ac'vely through appropriate na'onal policies that
understand and recognize its role and poten'al.
2. Strengthen the quality assurance, safety, proper use, and effec'veness of T&CM by regula'ng products, prac'ces, and
prac''oners through educa'on, training, and therapies.
3. Promote universal health coverage by integra'ng T&CM services into health service delivery and self-health care, allowing
informed choices about self-health care.

Areas iden?fied by WHO

• Safety and efficacy.
• Educa'on and training of prac''oners.
• Regula'on of prac'ces.
• Intellectual property.
• Research and development.
• Integra'on into health systems.
• Growing economic importance.

Tradi?onal & Complementary medicine

Tradi?onal medicine: It has a long history. It is the sum total of knowledge, skills, and prac'ces based on theories, beliefs, and
experiences indigenous to different cultures, used in health maintenance and the preven'on, diagnosis, improvement, or
treatment of physical and mental illness.
When adopted outside of its tradi'onal culture, tradi'onal medicine is ohen referred as “complementary and alterna've
medicine.”

Complementary medicine: Refers to health care prac'ces that are not part of a country's tradi'on or conven'onal medicine and
are not fully integrated into the dominant health-care system. They are used interchangeably with tradi'onal medicine in some
countries.

An Australian perspec?ve
• Na'onal Health and Medical Research Council Act 1992: Responsibili'es include the improvement of health, preven'on,
diagnosis, and treatment of disease, provision of health care, public health research, and medical research.
• Complementary medicines include vitamins, minerals, herbal, aromatherapy, and homoeopathic products. They may be
either listed or registered, depending on their ingredients and claims.

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Na?onal Health and Medical Research Council Act 1992,
Ü responsibility to inquire into, issue guidelines on, and advise the community on, maUers rela'ng to: the improvement of
health, the preven'on, diagnosis and treatment of disease, the provision of health care, public health research and
medical research and ethical issues rela'ng to health.
Ü all health treatments, whether conven'onal, tradi'onal or complementary, should be subject to a rigorous evalua'on of
the evidence for effec'veness. Complementary and Alterna've Medicine (CAM), also referred to as Complementary
Medicine (CM), are broad terms used to describe a wide range of health care medicines and therapies (forms of treatment
that do not involve medicines).
Ü Building the evidence base for CAM has been a commitment of NHMRC over of number of triennia, commencing in 2006.
A number of ini'a'ves have aimed to s'mulate research to inves'gate the use and effec'veness of CAM and strengthen
the integra'on of complementary and alterna've therapies into the health care system. NHMRC broadened its focus in
2012-2015 to ensure that all health treatments, whether conven'onal, tradi'onal or complementary, be subject to a
rigorous evalua'on of the evidence for their effec'veness. As such NHMRC commiUed to con'nuing to increase
knowledge through the funding of inves'gator-driven research on CAM.

Therapeu?c Goods Administra?on

Ü Complementary medicines (also known as 'tradi'onal' or 'alterna've' medicines) include vitamin, mineral, herbal,
aromatherapy and homoeopathic products.
Ü Complementary medicines may be either listed or registered, depending on their ingredients and the claims made.

What is modern medicine?

Terms used to describe modern scien'fic systems of medicine:
• Modern medicine
• Contemporary medicine
• Western medicine
• Science-based medicine
• Allopathic medicine
These systems aim to treat or prevent disease through pharmacological agents, physical interven'ons (surgery), psychotherapy,
medical devices, and ionizing radia'on.

What is Evidence?
• Evidence is ground for belief or disbelief; data on which to base proof or establish truth.
• In science, we rely on empirical evidence: informa'on acquired by observa'on or experimenta'on.
• Meaning varies based on context in science we rely on empirical evidence. Empirical evidence is informa'on acquired
by observa'on or experimenta'on. Experimenta'on > observa'on

What is evidence-based medicine?

Clinical decision-making was largely subjec've un'l the 1960s and 70s when the role of clinical reasoning was ques'oned. In the
1990s, the term evidence-based medicine was coined, describing a new approach to clinical decision-making.

Although all medicine based on science has some empirical underpinnings un'l rela'vely recently clinical decision making was
largely subjec've with individual medical prac''oners deciding on what research to consider and integra'ng that with their
personal
experience and beliefs.
In the 1960's and 70's a movement began where the role of clinical reasoning began to be ques'oned, prac''oner biases were
iden'fied, and it was pointed out that many treatments considered to be effec've had no controlled trials to support them. At this
'me

"clinical prac)ce was historically viewed as the “art of medicine.” Expert opinion, experience, and authoritarian judgment were the
founda)on for decision making. The use of scien)fic methodology, as in biomedical research, and sta)s)cal analysis, as in
epidemiology, were rare in the world of medicine." (Sur & Dahm, 2011)

In the 1990's the term evidence-based medicine was coined to describe a new approach to clinical decision-making. It is defined
as the conscien'ous, explicit and judicious use of current best evidence in making decision about the care of individual pa'ents.
It means integra'on individual clinical exper'se with the best available external clinical evidence from systema'c research. Cri'cs
of EBM suggest that the emphasis on randomised trials has limited usefulness for individual pa'ents however the evidence is one
of several considera'ons along with clinical experience and an individuals situa'on.

Evalua?ng clinical data

Factors to consider:
• The level of evidence: What type of study was done?

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 • The quality of the evidence: How well was the study done?
• The strength of the evidence: The magnitude of the effect, and how confident we are in the effect.

The level of evidence

What type of study?
• A well-established hierarchy of study designs for clinical interven'ons.
• Pyramid structure: most biased designs at the base leading to the least biased at the top.
• Divided into:
o Observa'onal studies (case reports, case-control, and cohort studies) vs experimental (randomized controlled
trial (RCT)).
o Analy'cal (RCT, cohort, and case-control studies) vs descrip've (Case reports, case series).
o Primary vs secondary.

The Quality of the Evidence

How well was the study done?
• Based on how well the research methods prevent results being affected by bias and confounding factors.
o Confounding factors are considered to be pa'ent features and other causal factors that can affect the outcome.
o Bias
1. How the subjects were selected
2. How the subjects were allocated to groups
3. Was there poten'al for bias in the way they were treated, maintained or followed up?
4. Was there poten'al for bias in the way measurements were made?
For study methods most likely to eliminate bias – remember RAMMbo

RAMMbo
• Recruitment: Who did the subjects represent? Were they representa've of the target popula'on? Was the sample large
enough? Were subjects recruited randomly or consecu'vely?
• Alloca'on: Was alloca'on to treatments randomized or matched? Were the groups similar at the start?
• Maintenance: Were the groups treated equally apart from the interven'on? Were outcomes ascertained and analysed
for Most pa'ents?
• Measurement: Were the measurements blind or objec've?

The Strength of the Evidence

"The strength of the evidence depends on the magnitude of the treatment effect seen in clinical studies and confidence
intervals. It also depends on how confident we are of the observed effect—in other words, the size of the confidence interval—
and the extent to which the findings have been reproduced across a series of studies. Strength of evidence is important for two
main reasons. Strong effects are less likely than weak effects to be the result of bias in the studies: they are more likely to be
real. And strong effects are more likely to be clinically important."
(NHMRC, 1998)

What do the results mean?

Outcome measures can be binary or con'nuous.
à Binary measures
o typically yes/no such as cancer, heart aUack ,stroke, death.
o typically reported as %, rates, rela've risk, absolute risk, hazard ra'os, odds ra'os, absolute risk reduc'on,
rela've risk reduc'on.
à Con'nuous measures
o vary along a con'nuum such as height, weight, cholesterol etc.
o These measures are typically reported as means.

Are the results real and relevant?

How do we know that the es'mate from a study sample is true for the popula'on? STATISTICS!!! – hypothesis tes'ng
* p-values = a measure of the probability that the result is purely due to chance. If your resul'ng probability is less than the
α level set, then the result is sta's'cally significant.
* Confidence intervals = es'ma'on. A confidence interval is an es'mate of the range of values likely to include the real
value. Usually quoted as a 95% confidence interval = range of values have a 95% chance of including the real value.
Typically more subjects = narrower CI
* NB: Sta's'cally significant does not necessarily mean clinically important and vice versa.

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Evidence vs. Authority:
As you become professionals this is a really important dis'nc'on to make. It is important to ques'on and not take things at face
value.
Just because the Harvard educated doctor says it - doesn't make it right or true. It is human nature to accede to an authority and
people can subconsciously bias their own data - make sure you start paying aUen'on to the difference.

How much of your lecturers material are you accep'ng based on authority rather than evidence!!! (Please don't start harassing
your lecturers but it's something you should
think about - are you following up with other sources).
Authority-based conclusions - arise from “opinion, experience, intui'on, judgement and scien'fic inference"
Evidence-based conclusions are “derived from an objec've, unbiased, and systema'c

RISK à the possibility of something bad happening the effect of uncertainty on objets
Absolute and Rela?ve Risk
• Absolute risk: Probability that a specified event will happen in a specified popula'on.
o E.g. 1 in 8 women will develop breast cancer in their life'me. Absolute risk = 12.5%.
o Increases with age.
• Rela?ve risk compares the risk in one group rela've to another:
o A rela've risk of 1 means no difference in risk between groups.
o RR < 1 means the event is less likely in the experimental group.
o RR > 1 means the event is more likely to occur in the experimental group than in the control group
• Repor?ng risk
o Compared to women who do not drink, women who have two or more drinks per day have a 25% higher risk of
breast cancer (media)
o Compared to women who do not drink, women who have two or more drinks per day have a rela've risk of 1.25
(research study).
o 25% increase sounds huge BUT rela've risk = 1.25
o Absolute risk is 12.5%
o 12.5% x 1.25 = 15.63% absolute risk compared with 12.5% if you don’t drink
o LOOK CASES!!

Odds Ra?o
• The ra'o of the odds of an event occurring in one group to the odds of it occurring in another.
• Describes the strength of associa'on (so retrospec've)
• The ra'o of the “odds” of an event occurring in one group compared with the “odds” of the event occurring in another
group
• Ohen used interchangeably with rela've risk – it is NOT the same

à If the effect is small than the odds and rela've risk are close (If disease occurs 1 in 100: risk is 1/100 = 0.01; Odds are 1 to
99 = 0.0101)
à If the effect is large (>5%) than OR is not a good es'mate of the risk ra'o. (if disease occurs 70 in 100: Risk is 70/100 =
0.7; Odds are 70/30 = 2.33)

LESSON 3: NUTRITIONAL SUPLEMENTS

Poten?al harms of supplements:
• Common belief that they are natural and therefore harmless.
• Poor quality control – not what it says; contaminants.
1. Adverse effects.
2. Drug interac'ons.
3. Delay of other evidence-based therapy.
4. Cost of ineffec've treatments and waste of health dollar.
5. Psychological effects – disappointment, disillusionment, depression => compliance problems with subsequent
evidence-based therapy.

Vitamin supplements:
• Dietary supplements containing vitamins and minerals were the most popular type of complementary medicine.
• Vitamins and minerals are generally used safely when prescribed in medical se;ngs for the treatment or preven'on of
deficiency states and other appropriate condi'ons.

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 o For example, vitamin B3 is used for hyperlipidaemias, and folic acid is used in pregnancy to prevent birth defects.
• The key to the safety of vitamins and minerals is the prescribed dose, which is usually derived from research
demonstra'ng that the benefits outweigh the harms.
• Vitamins are organic compounds that our bodies use, in very small amounts, for a variety of metabolic processes. It is
best to get vitamins and minerals from ea'ng a variety of healthy unprocessed foods.
• Research indicates that most of the vitamins you get from the food you eat are beUer than those contained in pills.
o The main excep'on to this is folate. The synthe'c form (in a supplement or for'fied food) is beUer absorbed by
the body than folate from food sources.
• Food is a complex source of vitamins, minerals, and phytochemicals (plant chemicals), which all work together.
Supplements tend to work in isola'on. Research shows a food component that has an effect on the body may not have
the same effect when it is isolated and taken as a supplement.

Vitamin and mineral deficiencies:

Our body only needs a small amount of vitamins and minerals every day. A varied diet generally provides enough of each vitamin
and mineral. However, some people may need supplements to correct vitamin or mineral deficiencies and this includes:
• Pregnant women and women who are breaspeeding.
• People who smoke, drink alcohol in excess, or use illegal drugs.
• Crash dieters or those on very strict diets.
• The elderly (especially those who are disabled or chronically ill).
• Some vegetarians or vegans.
• Women with heavy periods.
• People with food allergies.
• Those with malabsorp'on problems (such as diarrhoea, coeliac disease, cys'c fibrosis, or pancrea''s).

Folate and pregnancy:

• Women who are pregnant or planning a pregnancy are recommended folic acid (also known as folate) supplements to
reduce their risk of having a child with a neural tube defect, such as spina bifida.
• Folic acid is a B-group vitamin, which can also be found in some for'fied foods such as breads and breakfast cereals. Foods
for'fied with folic acid have the nutrient added to them during produc'on to boost their nutri'onal value.

Vegan diets and vitamin supplements:

• People who follow vegan diets, especially if pregnant, may benefit from vitamin B12 supplements.

Safety:
High doses of vitamin supplements are unsafe
• Many people mistakenly believe that since small amounts of vitamins are good for you, then large amounts must be
beUer. However, it is beUer to follow the rule of ‘less is more.’
• Taking higher than recommended doses of some vitamins may cause health problems, such as:
o Vitamins A, D, E, and K are fat-soluble, which means they are stored in the body and if taken in high doses can
be toxic.
o High doses of vitamin A may cause birth defects, as well as central nervous system, liver, bone, and skin disorders.
o Very high doses of vitamin D may cause hypercalcaemia, with symptoms ranging from thirst and polyuria to
seizures, coma, and death. High intermiUent doses of vitamin D have been associated with increased risk of falls
and fractures in the elderly.
o An'platelet effects and increased risk of haemorrhagic stroke are associated with excess Vitamin E.
• High doses of some water-soluble vitamins can also become toxic.
o Large folate intakes can hide vitamin B12 deficiencies.
o High levels of vitamin B6 have also been linked to some types of nerve damage.
o Large doses of vitamin C may also cause nausea, abdominal cramps, headaches, fa'gue, kidney stones, and
interfere with your body’s ability to process (metabolise) other nutrients – such as dangerously raising your iron
levels.
o Excessive amounts of vitamin C in the body can also interfere with medical tests – such as diabetes tests, by
giving a false result.

Large doses of minerals can also lead to health problems

Excessive doses of some minerals may also cause problems. For example:
* At just five 'mes the RDI, zinc, iron, chromium, and selenium can be raised to toxic levels in the body.
* Large intakes of fluoride (especially in childhood) may stain and even weaken the teeth.
* Very large doses of fish oil can lead to decreased blood clo;ng.

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 * Iron toxicity is common. Even a small amount over the RDI can cause gastrointes'nal upset, nausea, and black bowel
ac'ons (poo). Severe toxicity can lead to coma and death.
* Calcium
Carbonate salt can cause gastric reflux and cons'pa'on. High-dose calcium may induce vascular and soh 'ssue
calcifica'on, hypercalciuria, kidney stones and secondary hypoparathyroidism. Interferes with absorp'on of magnesium,
iron and zinc if taken simultaneously, and can reduce absorp'on of many other drugs e.g. levothyroxine, tetracyclines.
* Magnesium
High doses ohen result in diarrhoea, nausea and abdominal cramping due to the osmo'c effect. Like other divalent
ca'ons, magnesium may chelate and reduce absorp'on of other minerals or medicines such as tetracyclines.
* Zinc
Ohen associated with altered or impaired taste and smell. Intranasal zinc can cause anosmia. Doses ≥80 mg/day in clinical
trials were associated with adverse prostate effects.
* Selenium
Associated with acute and chronic toxicity. Signs of chronic high-dose ‘selenosis’ are hair and nail loss or briUleness, lesions
of the skin and nervous system, nausea, diarrhoea, skin rashes, moUled teeth, fa'gue and mood irritability.

For?fica?on of foods
Mandatory for?fica?on:
• Standard 2.1.1 - Cereals and Cereal Products require the addi'on of thiamin and folic acid to wheat flour for making bread
(Australia only) and the replacement of salt with iodised salt in bread.
• Standard 2.4.2 - Edible Oil Spreads requires the addi'on of vitamin D to margarines and spreads (Australia only).

Voluntary for?fica?on
• Most vitamin and mineral permissions can be found in Standard 1.3.2 – Vitamins and Minerals but other standards also
permit vitamin and mineral addi'on.
• Standard 2.6.2 –Non-Alcoholic Beverages and Brewed Soh Drinks permits manufacturers to add fluoride to boUled
water.
• Standard 2.6.4 – Formulated Caffeinated Beverages permits manufacturers to add certain vitamins to formulated
caffeinated beverages.
• Standard 2.10.2 – Salt and Salt Products permits iodine to be added to salt.
• Standard 2.10.3 – Chewing Gum gives permission to add calcium to chewing gum.
• There are also standards in Part 2.9 of the Code that permit or require vitamins and minerals to be added to ‘Special
Purpose’

Vitamin A
Roles:
• Involved in immune func'on, vision, reproduc'on, and cellular communica'on.
• Cri'cal for vision as an essen'al component of rhodopsin, a protein that absorbs light in the re'nal receptors, and because
it supports the normal differen'a'on and func'oning of the conjunc'val membranes and cornea.
• Supports cell growth and differen'a'on, playing a cri'cal role in the normal forma'on and maintenance of the heart,
lungs, kidneys, and other organs.

Sources:
• Preformed Vitamin A – meat, poultry, fish, dairy products.
• Provitamin A (most common = beta-carotene) – fruits, vegetables, and other plant-based products

Deficiency:
• More likely in premature infants, young children, pregnant women, breaspeeding women in developing countries, and
people with cys'c fibrosis.
• Vitamin A supplements can shorten the fever and diarrhea caused by measles in children with vitamin A deficiency and
lower the risk of death in developing countries.

Safety:
• High intakes of some forms of vitamin A can be harmful. too much preformed vitamin A (usually from supplements or
certain medicines) can cause dizziness, nausea, headaches, coma, and even death.
• High intakes of preformed vitamin A in pregnant women can also cause birth defects in their babies
• Consuming high amounts of beta-carotene or other forms of provitamin A can turn the skin yellow-orange, but this
condi'on is harmless. High intakes of beta-carotene do not cause birth defects or the other more serious effects caused
by ge;ng too much preformed vitamin A

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Interac'ons:
• Orlistat, a weight-loss drug, can decrease the absorp'on of vitamin A, causing low blood levels in some people.
• Several synthe'c forms of vitamin A are used in prescrip'on medicines. E.g. the psoriasis treatment acitre'n and
bexarotene, used to treat the skin effects of T-cell lymphoma. Taking these medicines in combina'on with a vitamin A
supplement can cause dangerously high levels of Vit A in the blood.

Thiamine (Vitamin B1)

Role:
• Plays a cri'cal role in energy metabolism and the growth, development, and func'on of cells.
Sources:
• Whole grains, meat (especially pork), fish, legumes, seeds, and nuts.
• For'fied in breads, cereals, and infant formulas.
Deficiency:
• Higher likelihood in older individuals, people with diabetes, HIV/AIDs, alcohol dependence, and those who have had
bariatric surgery.
• Can cause loss of weight, appe'te, confusion, memory loss, muscle weakness, and heart problems.
• Severe deficiency can lead to beriberi (with the added symptoms of 'ngling and numbness in the feet and
• hands, loss of muscle, and poor reflexes) and Wernicke-Korsakoff syndrome in people with alcoholism (It causes 'ngling
and numbness in the hands and feet, severe memory loss, disorienta'on, and confusion)
Safety:
• No known harm from thiamine supplementa'on.
Interac'ons:
• Some medica'ons, such as furosemide and fluorouracil, can decrease thiamine levels.

Riboflavin (Vitamin B2)

Role:
• Involved in the body's energy produc'on, cellular func'on, growth, and development.
• essen'al component of two major coenzymes, flavin mononucleo'de (FMN) and flavin adenine dinucleo'de (FAD). These
coenzymes play major roles in energy produc'on; cellular func'on, growth, and development; and metabolism of fats,
drugs, and steroids.
• conversion of the amino acid tryptophan to niacin (B3) requires FAD
• conversion of vitamin B6 to the coenzyme pyridoxal 5’-phosphate needs FMN.
• riboflavin helps maintain normal levels of homocysteine, an amino acid in the blood à important for the growth,
development, and func'on of the cells in your body. It also helps turn the food you eat into the energy you need.

Sources:
• Eggs, organ meats (liver and kidney), lean meats, milk, and green vegetables.
• For'fied cereals, bread, and grain products

Deficiency:
• Not common but can occur in people with malabsorp've disorders.
• Higher likelihood in athletes who are vegetarians, pregnant women, breaspeeding women and their babies, people who
are vegan, people who do not eat dairy foods, people with a gene'c disorder called riboflavin transporter deficiency
(prevents the body from properly absorbing and using riboflavin)
• The signs and symptoms of riboflavin deficiency include skin disorders, hyperemia (excess blood) and edema of the mouth
and throat, angular stoma''s (lesions at the corners of the mouth), cheilosis (swollen, cracked lips), hair loss, reproduc've
problems, sore throat, itchy and red eyes, and degenera'on of the liver and nervous system.
• People with riboflavin deficiency typically have deficiencies of other nutrients, so some of these signs and symptoms
might reflect these other deficiencies.
• Severe riboflavin deficiency can impair the metabolism of other nutrients, especially other B vitamins, through diminished
levels of flavin coenzymes
• Anaemia and cataracts can develop if riboflavin deficiency is severe and prolonged
• The earlier changes associated with riboflavin deficiency are easily reversed. However, riboflavin supplements rarely
reverse later anatomical changes (such as forma'on of cataract
Safety:
• Riboflavin is generally considered safe, even at high doses.

Vitamin C
Role:
• Important for growth, development, and repair of body 'ssues.

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Sources:
• Citrus fruits, strawberries, broccoli, and potatoes.
Deficiency:
• Can lead to scurvy, causing anemia, debility, exhaus'on, spontaneous bleeding, pain in the limbs, and swelling in some
parts of the body.
Safety:
• Large doses can lead to stomach cramps, nausea, and diarrhea.

Niacin (Vitamin B3)

Role:
• Converts food into energy.
• Supports proper func'oning of the diges've system, skin, and nerves.
Sources:
• Chicken, turkey, tuna, salmon, and for'fied cereals.
Deficiency:
• Pellagra: Symptoms include diarrhea, derma''s, demen'a, and can result in death.
Safety:
• Excessive intake can lead to liver damage, pep'c ulcers, and skin rashes.

Pantothenic Acid (Vitamin B5)

Role:
• Essen'al for the synthesis of coenzyme A (CoA), a key molecule in faUy acid metabolism.
Sources:
• Almost all food groups, including meat, vegetables, cereals, and legumes.
Deficiency:
• Rare, but may lead to symptoms like fa'gue, insomnia, and depression.
Safety:
• Generally safe with no known toxicity.

Vitamin B6 (Pyridoxine)
Role:
• Important for normal brain development and func'on, and helps the body convert food into energy.
• Vitamin B6 also plays a role in cogni've development through the biosynthesis of neurotransmiUers and in maintaining
normal levels of homocysteine, an amino acid in the blood
• Vitamin B6 is involved in gluconeogenesis and glycogenolysis, immune func'on and haemoglobin forma'on
Sources:
• Fish, beef liver, potatoes, and starchy vegetables.
Deficiency:
• Can cause anemia, derma''s, depression, and a weakened immune response.
Safety:
• High doses can lead to nerve damage.

Bio?n (Vitamin B7)

Role:
• Plays a cri'cal role in metabolism, helping to convert food into energy.
Sources:
• Eggs, fish, meat, seeds, nuts, and certain vegetables (e.g., spinach).
Deficiency:
• Can cause hair thinning, rash, neurological symptoms, and in severe cases, seizures.
Safety:
• Generally safe with no known toxicity.

Folate (Vitamin B9)

Role:
• Vital for making DNA and RNA, and is par'cularly important during periods of rapid growth, such as pregnancy and
infancy.
Sources:
• Leafy greens, citrus fruits, beans, peas, and for'fied cereals.
Deficiency:
• Can lead to anemia, fa'gue, and in pregnant women, increases the risk of neural tube defects in infants.

9
Safety:
• High doses of folic acid may mask the symptoms of vitamin B12 deficiency.

Vitamin B12 (Cobalamin)

Role:
• Essen'al for blood forma'on, neurological func'on, and DNA synthesis.
Sources:
• Fish, meat, poultry, eggs, milk, and for'fied cereals.
Deficiency:
• Can cause megaloblas'c anemia, fa'gue, weakness, cons'pa'on, loss of appe'te, and nerve damage.
Safety:
• Generally safe, even at high doses.

Vitamin D
Role:
• Helps the body absorb calcium, which is cri'cal for bone health.
• Supports the immune system and muscle func'on.
Sources:
• Sunlight exposure, for'fied foods, faUy fish, and egg yolks.
Deficiency:
• Can cause rickets in children and osteomalacia in adults, leading to soh, thin, and briUle bones.
Safety:
• Excessive intake can cause calcium buildup, leading to kidney damage.

Vitamin E
Role:
• Acts as an an'oxidant, protec'ng cells from damage caused by free radicals.
Sources:
• Nuts, seeds, vegetable oils, and green leafy vegetables.
Deficiency:
• Rare but can cause nerve and muscle damage, vision problems, and a weakened immune system.
Safety:
• High doses may increase the risk of bleeding.

Vitamin K
Role:
• Essen'al for blood clo;ng and bone health.
Sources:
• Leafy green vegetables like spinach and kale, broccoli, and Brussels sprouts.
Deficiency:
• Can lead to excessive bleeding.
Safety:
• Generally safe, but can interfere with blood-thinning medica'ons.

Calcium
Role:
• Essen'al for bone health, muscle func'on, and nerve transmission.
Sources:
• Dairy products, for'fied foods, leafy green vegetables, and fish with soh bones (like sardines and salmon).
Safety:
• Excessive calcium intake can cause kidney stones, vascular calcifica'on, and impair the absorp'on of other nutrients like
magnesium and iron.
Interac'ons:
• Calcium can reduce the absorp'on of these drugs when taken together:
o Bisphosphonates (to treat osteoporosis) , An'bio'cs of the fluoroquinolone and tetracycline families,
Levothyroxine (to treat low thyroid ac'vity), Phenytoin (an an'convulsant), Tiludronate disodium (to treat
Paget’s disease).,
• Diure'cs differ in their effects.
o Thiazide-type diure'cs reduce calcium excre'on by the kidneys which in turn can raise blood calcium levels
too high.

10
 o loop diure'cs increase calcium excre'on and thereby lower blood calcium levels.
• Antacids containing aluminum or magnesium increase calcium loss in the urine.
• Mineral oil and s'mulant laxa'ves reduce calcium absorp'on.
• Glucocor'coids can cause calcium deple'on and eventually osteoporosis when people use them for months at a 'me.

Iron
Role:
• Cri'cal for the produc'on of hemoglobin, which carries oxygen in the blood.
Sources:
• Red meat, poultry, fish, beans, len'ls, and for'fied cereals.
Deficiency:
• Can cause iron-deficiency anemia, leading to fa'gue, weakness, and pale skin.
Safety:
• Excessive intake can lead to iron toxicity, causing liver damage and other health issues.

Manganese
Role:
• Involved in bone forma'on, blood clo;ng, and reducing inflamma'on.
Sources:
• Whole grains, nuts, leafy vegetables, and tea.
Deficiency:
• Rare, but can affect bone forma'on and reproduc've health.
Safety:
• High levels can cause neurological problems, especially in individuals exposed to manganese dust.

Zinc
Role:
• Supports immune func'on, protein synthesis, wound healing, and DNA synthesis.
Sources:
• Meat, shellfish, legumes, and seeds.
Deficiency:
• Can lead to hair loss, delayed wound healing, impaired taste, and diarrhea.
Safety:
• Excessive intake can cause nausea, vomi'ng, and interfere with copper absorp'on.

Magnesium
Role:
• Involved in over 300 biochemical reac'ons in the body, including muscle and nerve func'on, blood sugar control, and
blood pressure regula'on.
Sources:
• Leafy greens, nuts, seeds, whole grains, and legumes.
Deficiency:
• Can cause muscle cramps, mental disorders, osteoporosis, and fa'gue.
Safety:
• High doses can lead to diarrhea, nausea, and abdominal cramping.

Selenium
Role:
• Plays a key role in metabolism and thyroid func'on, and helps protect the body from oxida've stress.
Sources:
• Brazil nuts, seafood, meat, and eggs.
Deficiency:
• Rare but can cause Keshan disease (a heart disease) and male infer'lity.
Safety:
• High doses can lead to selenium toxicity, causing hair loss, gastrointes'nal issues, and nervous system abnormali'es.

IN SUMMARY:
ù In developed countries vitamin and mineral deficiencies are uncommon excep'ons may include:

11
 o Vitamin D
o Vitamin B12
o Iron
o Vitamin E?
o Mg2+?
ù Overuse is frequently harmful
ù Supplementa'on should not really be necessary unless under medical advice.
ù Specific groups are at risk– vary
o When need increases – pregnancy, breast feeding, childhood, adolescence,
o When absorp'on decreases – elderly, malabsorp'on disorders,
o dietary groups,
o Specific illnesses including alcohol dependence
ù Interac'ons – are frequent and varied
o An'-coagulants
o Orlistat
o An'bio'cs
o Thyroid medica'ons
o Epilepsy medica'ons

LESSON 4:

Arthri?s
• Swelling or tenderness of one or more joints => joint pain and s'ffness
• Typically worsens with age
• Different types = different causes (wear and tear, infec'ons, underlying disease)
o Degenera've
o Inflammatory
o Infec'ous
o Metabolic

Osteoarthri?s: Degenera've, car'lage on ends of bones wears away => bone rubs against bone => swelling, pain & s'ffness
Rheumatoid arthri?s: Autoimmune disease where immune system aUacks the joints, inflammatory, poten'ally causing erosion of
joints.

Glucosamine and Chondroi?n

• Frequently together
• Thought may relieve pain and prevent or slow car'lage breakdown in osteoarthri's.
• Dietary supplement in Aus, U.S.
• Approved medicine in Europe

Helps relieve:
• Symptoms of mild osteoarthri's
• Mild joint pain
• Mild joint s'ffness
• Relieves symptoms of mild arthri's; relieves mild joint aches and pains and supports joint mobility
• Cushions joints and supports movements, hels promote healthy car'lage

Glucosamine
• Amino sugar – one of the most abundant monosaccharides
• Precursor in biochemical synthesis of glycosylated proteins and lipids
• Precursor of all nitrogen-containing sugars
• Part of the structure of two polysaccharides, chitosan and chi'n

UDP-GlcNAc à glycosaminoglycans, proteoglycans, and glycolipids.

• Glycosaminoglycans are a major component of car'lage
• Classified into 4 groups based on core disaccharide structures
1. Heparin/heparin sulphate
2. Chondroi'n sulphate/dermatan sulphate
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 3. Ketaran sulphate
4. Hyaluronic acid

Chondroi?n for osteoarthri?s:

43 studies - 9,110 people (<November 2013). Majority – knee osteoarthri's; 1m – 3y
Several studies were funded by makers of chondroi'n.
This review shows that in people with osteoarthri's:
o Chondroi'n may improve pain slightly in the short-term (less than 6 months);
o Chondroi'n improves knee pain by 20% in slightly more people;
o Chondroi'n probably improves quality of life slightly as measured by Lequesne's index (combined measure of
pain, func'on, and disability);
o Chondroi'n has liUle or no difference in adverse and serious adverse events versus other agent
o Chondroi'n slightly slows down the narrowing of joint space on X-rays of the affected joint.
o We iden'fied a lot of studies in which unsound methods were used to assess the effects of chondroi'n
o For some outcomes, there was not enough data. In some studies, whose methodological quality was beUer,
chondroi'n showed no improvement in pain and in physical func'on. Other analyses based on different
methodological quality criteria reported improvement in pain and physical func'onality when chondroi'n was
given.

RACGP recommenda'ons
ù We suggest not offering glucosamine for people with knee and/or hip osteoarthri's (OA).
ù We suggest not offering chondroi'n for people with knee and/or hip OA.
ù We suggest not offering glucosamine and chondroi'n in compound form for people with knee and/or hip OA.

Chondroi?n sulfate
• A sulfated glycosaminoglycan composed of a chain of alterna'ng sugars (N-acetylgalactosamine and glucuronic acid).
• Found aUached to proteins as part of a proteoglycan.
• An important structural component of car'lage, providing resistance to compression
• High variability in terms of chain lenght and sulpha'on paUern

Bioavailability
• Chondroi'n sulfate (15-24%), labeled chondroi'n sulfate is found in synovial fluid and car'lage.
• Glucosamine plasma and synovial fluid concentra'ons increased following 1,500 mg glucosamine sulfate daily for two
weeks (n=12).
Safety
• Generally considered quite safe.
• Side effects: upset stomach (diarrhea), headaches, and skin reac'ons.

Cau?ons
- may interact with the an'coagulant (blood-thinning) drug warfarin
- Shellfish allergy: most glucosamine supplements are made from shellfish, although some made from non-shellfish sources
are now available
- Glucosamine might affect the way your body handles sugar, especially if you have diabetes or other blood sugar problems,
such as insulin resistance or impaired glucose tolerance.
- come from animal sources => unsafe manufacturing prac'ces might lead to contamina'on with diseased animal 'ssues
- A study in rats showed that long-term use of moderately large doses of glucosamine might damage the kidneys –
applicability to humans unknown
- Chondroi'n sulphate is not metabolized by cytochrome P450

Echinacea
• The name of a group of flowering plants in the daisy family.
• A herb na've to areas east of the Rocky Mountains in the United States.
• Nine known species, na've to North America.
• Used by Na've Americans as tradi'onal medicines.
Today
• Echinacea is promoted as a dietary supplement/herbal remedy for the common cold or flu.
• It's also used to treat pain, inflamma'on, migraines, and other health issues.
• Prepara'ons for topical use (applica'on to the skin) for wounds and skin problems.

13
Common uses:
• Widely used to fight infec'ons, especially the common cold, flu, and upper respiratory infec'ons.
o Relieves symptoms of common colds and flu
o Helps reduce severity and dura'on of common colds
o Promote immune system defense
o Immune support
o Tradi'onally use in Western herbal medicine to relieve symptoms of mild upper respiratory tract infec'ons
• Echinacea is also used against many other infec'ons including urinary tract infec'ons, vaginal yeast infec'ons, herpes,
HIV/AIDS, human papilloma virus (HPV), bloodstream infec'ons (sep'caemia), tonsilli's, streptococcus infec'ons,
syphilis, typhoid, malaria, ear infec'on, swine flu, warts, and nose and throat infec'ons called diphtheria.
• Other uses include anxiety, low white blood cell count, chronic fa'gue syndrome (CFS), rheumatoid arthri's, migraines,
acid indiges'on, pain, dizziness, raUlesnake bites, aUen'on deficit-hyperac'vity disorder (ADHD), and improving exercise
performance.
• Some'mes people apply echinacea to their skin to treat boils, gum disease, abscesses, skin wounds, ulcers, burns,
eczema, psoriasis, sun-related skin damage, herpes simplex, yeast infec'ons, bee s'ngs, snake and mosquito bites, and
hemorrhoids.
• Echinacea is also used as an injec'on to treat vaginal yeast infec'ons and urinary tract infec'ons (UTIs).

Research
• Echinacea species have been shown to have several phytochemicals.
• Bioac'vi'es include an'oxidant, immunomodulatory, an'-inflammatory, an'fungal, and an'viral proper'es.
• Other areas of research are:
o Blood sugar levels à supress enzymes that digest carbohydrates, made cells more sensi've to insulin’s effect by
inac'va'ng a common target of diabetes drugs (PPAR-y)
o Anxiety à rapidly reduce feelings of anxiety
o Skin concerns à an'-infammatory and an'-bacterial propier'es, skin care products improve skin hydra'on and
reduce wrinkles. Improve eczema symptoms and helps repair outer layer of skin. It has a short shelf life so its
difficult to add id on skin care producs
o Cancer à can trigger cancer cell death, s'mula'ng apoptosis due to it boost immune propier'es.
Safety:
• Some side effects such as nausea, vomi'ng, stomach pain, diarrhea, dry mouth, headache, diziness… in rare cases
inflamma'on of the liver
• Can cause allergic reac'ons
• Is likely safe for most people
• Precau'ons in children, pregnancy, breast feeding, atopies and autoimmune disorders

Turmeric
• Curcuma longa: A flowering, perennial, herbaceous, and rhizomatous plant.
• Used as a spice in cooking and in tradi'onal medicine for its therapeu'c effects.
o In tradi'onal medicine, turmeric is prescribed for some respiratory disorders, sinusi's, allergy, anorexia, and liver
problems
o In ancient 'mes in the Far East, turmeric was used to treat inflammatory condi'ons of various organs, for liver
and diges've tract problems, and on wound healing, disorders of the skin, upper respiratory tract, joints,
arthri's, and in dyslipidemia
• turmeric is promoted as a dietary supplement for a variety of condi'ons, including joint pain in arthri's, fibromyalgia,
various diges've disorders, gallbladder disorders, respiratory infec'ons, allergies, jaundice and other liver disease,
menstrual problems, depression, Alzheimer's disease, high cholesterol, itchy skin, a skin condi'on called lichen planus,
skin inflamma'on from radia'on treatment, and fa'gue., swelling in the middle layer of the eye (anterior uvei's),
diabetes, water reten'on, worms, systemic lupus erythematosus (SLE), tuberculosis, urinary bladder inflamma'on, and
kidney problems.
• Some people apply turmeric to the skin for pain, ringworm, sprains and swellings, bruising, leech bites, eye infec'ons,
acne, inflammatory skin condi'ons and skin sores, soreness inside of the mouth, infected wounds..

Curcumin
• The main polyphenol of Curcuma longa and other Curcuma species.
• An'-inflammatory and an'oxidant proper'es.
• Has been reported to target several signaling molecules at the cellular level, suppor'ng its medical advantages.
• As an an'oxidant, curcumin directly scavengers ROS and acts indirectly by triggering an'oxidant reac'ons
• an'-inflammatory and an'apopto'c effects

14
 o inhibi'ng lipoxygenase 5 (5-LOX), peroxisome proliferator–ac'vated receptor, IL-6, IL-8, IL-12, COX-2, TNF-α, MAP
kinase, adaptor protein-1 (AP-1), NF-ĸB, phosphorylase kinase, cAMP–dependent protein kinase, EGF, EGF
receptor kinase, and iNOS
o inflammatory atherogenic cytokines such as IL-1α, IL-6, and TNF-α, are inhibited by curcumin via inhibi'on of the
ac'vity of an'-inflammatory enzyme heme oxygenase-1 by suppression of NF-κB and AP-1 transcrip'on factors
=> possible modula'on of the atherogenic ac'vi'es of inflammatory monocytes.
• Arthri's pain relief, an'-inflammatory, diges've health

LESSON 5: NUTRACEUTICALS USED FOR SLEEP, ANXIETY, AND DEPRESSION

Synthesis of Melatonin
• GABA is an inhibitory neurotransmiUer.
• The GABA-A receptor is an ion channel-coupled
receptor.

Sleep
• Many and varied components.
• Some common herbs.
• Frequently minerals.

Sleep Sound Ac?ve Ingredients: RESTLESS SLEEP

• Valeriana officinalis (valerian) extract dry conc. 300
mg equiv. dry root 1.2 g (1200 mg).
• Melissa officinalis (lemon balm) extract dry conc.
211.54 mg equiv. dry leaf 825 mg.
• Magnesium phosphate pentahydrate (magnesium
55 mg) 266.2 mg.

Sleep Sound Magnesium Ac?ve Ingredients: MUSCLE CREAMPS

• Magnesium citrate (magnesium 296 mg) 2 g (2000 mg), Magnesium glycinate dihydrate (magnesium 24 mg) 216 mg (Total
magnesium 320 mg).
• Glycine 3.1 g (3100 mg).
• Humulus lupulus (hops) extract dry conc. 125 mg equiv. to dry flower 937.5 mg.
• Calcium citrate tetrahydrate (calcium 133.2 mg) 634 mg.

Tranquil Night Ac?ve Ingredients: BUSY MIND

• Lavendula angus)folia (lavender) extract dry conc. 150 mg equiv. dry flower 600 mg.
• Humulus lupulus (hops) extract dry conc. 33.34 mg equiv. dry fruit 250 mg.
• Passiflora incarnata (passionflower) extract dry conc. 50 mg equiv. herb dry 250 mg.
• Avena sa)va (oats) extract dry conc. 25 mg equiv. herb fresh 250 mg.

Valerian Forte Ac?ve Ingredients: WAKING UP TIRED

• Valerian officinalis (valerian) extract dry conc. 400 mg equiv. to dry root and rhizome 2 g (2000 mg) standardised to contain
valerenic acids 3.2 mg.

Sleep-Ezy
• Valeriana officinalis dry root extract 139 mg, from 556 mg dry root (Valerian).
• Humulus lupulus dry flower extract 33.33 mg, from 250 mg dry flower (Hops).
• Matricaria chamomilla dry flower extract 25 mg, from 100 mg dry flower (Chamomile).
• Passiflora incarnata dry herb extract 18.18 mg, from 100 mg dry herb (Passion Flower).
• Calcium (from Calcium Hydrogen Phosphate dihydrate) 23.3 mg.
• Magnesium (from Magnesium Phosphate Pentahydrate) 10.4 mg.

Complete Sleep Advanced

• Alpha casozepine enriched hydrolysed milk protein (Lac)um®) 112.5 mg.
• Ziziphus jujuba var. spinosa dry seed extract 450 mg, from 4.5 g dry seed (Spine Date).
• Humulus lupulus dry flower extract 66.67 mg, from 500 mg dry flower (Hops).
• Valeriana officinalis dry root extract 500 mg, from 2 g dry root (Valerian).

15
Common Herbs Used for Sleep & Anxiety
• Valeriana officinalis (Valerian).
• Passiflora incarnata (Passion Flower).
• Melissa officinalis (Lemon Balm).
• Matricaria chamomilla (Chamomile).
• Humulus lupulus (Hops).
• Mg²⁺ & Ca²⁺.
• Ziziphus jujuba var. spinosa (Spine Date).
• Lavendula angus)folia.
• Avena sa)va (Oats).
• Alpha casozepine enriched hydrolysed milk protein (Lac)um®).
• Kava.

Valerian
• Valeriana officinalis – perennial flowering plant na've to Europe and Asia; it also grows in North America.
• Historically used to treat insomnia, migraine, fa'gue, and stomach cramps.
• Valerian is promoted for insomnia, anxiety, depression, PMS, menopause symptoms, and headaches.
• Ohen combined with hops, lemon balm, or other herbs causing drowsiness.
• Exact mechanism unknown.
• Broad range of bioac've compounds iden'fied, but no consensus on specifics.
• The evidence on whether valerian is helpful for sleep problems is inconsistent.

Systema?c Reviews on Valerian

• 2000: 9 trials – contradictory and inconsistency in design and quality => inconclusive.
• 2006: 16 trials – methodological problems, valerian doses, prepara'ons, and length of treatment varied considerably.
o Available evidence suggests valerian might improve sleep quality without side effects.
• 2007: 37 studies – most found no significant differences between valerian and placebo in sleep disturbance or insomnia.
• 2020: 60 studies – inconsistent outcomes due to the variable quality of herbal extracts; therapeu'c benefits could be
op'mized when combined with herbal partners.
• No severe adverse events associated with valerian intake.

Passiflora Incarnata (Passionflower)

• Used historically by Na've Americans for various condi'ons, including boils, wounds, and liver problems.
• Promoted today for insomnia, anxiety, and sleep problems.
• Evidence suggests CNS depressant effects, though opinions differ on the bioac'vity.

Matricaria Recu?ta (Chamomile)

• Commonly used for sleeplessness, anxiety, and gastrointes'nal condi'ons.
• Research suggests an'-spasmodic, anxioly'c, an'-inflammatory, and cholesterol-lowering effects.
• A 2020 systema'c review found increased sleep quality in elderly people suffering from sleep disorders.

Humulus Lupulus (Hops)

• Tradi'onal use of hops as a mild seda've dates back to Na've American tribes.
• Used in beer brewing and topically for various condi'ons.
• Contains bioac've compounds with seda'ng proper'es, but no clinical trials have confirmed this.

Avena Sa?va (Oats)

• Tradi'onally used for nervous exhaus'on, insomnia, and nervous weakness.
• Oats possess an'oxidant, an'-inflammatory, and wound-healing proper'es.

Lac?um™
• Derived from milk protein and claimed to have anxioly'c effects.
• May work as a GABA-A agonist.

Ziziphus Jujuba Var. Spinosa (Spine Date)

• Used in tradi'onal Chinese medicine for insomnia and anxiety.
• Shows CNS effects on sleep, anxiety, and neuroprotec'on.

Kava (Piper Methys?cum)

• Na've to the Pacific islands, used tradi'onally for medicinal and ritual purposes.
16
 • Used as an an'-anxiety treatment in the Western world.
• Contains kavalactones, which affect GABAA receptors and may inhibit the reuptake of noradrenaline and dopamine.
• Studies show some effec'veness in reducing anxiety.

St. John’s Wort

• Tradi'onally used for depression, anxiety, and other condi'ons.
• Bioac've compounds include flavonoids and hypericin, which may inhibit serotonin reuptake and other mechanisms.
• Shown to be effec've for mild and moderate depression but may interact dangerously with medica'ons

Other common nutraceu'cals for depression

5HTP = 5-hydroxytryptophan
Naturally occurring amino acid
Precursor for 5HT
Dietary supplement for use in depression, appe'te suppression and sleep.
5HTP cross BBB – 5HT does not
As of 25 August 2020, Hungary added 5-HTP to the controlled psychoac've substances list, prohibi'ng produc'on, sale,
import, storage and use, becoming first country to do so

SAM-e = S-adenosyl methionine

Co-substrate involved in methyl group transfers, trans-sulphura'on, amino- propyla'on
A 2016 Cochrane review concluded that for major depressive disorder, "Given the absence of high quality evidence and
the inability to draw firm conclusions based on that evidence, the use of SAMe for the treatment of depression in adults
should be inves'gated further."
A 2020 systema'c review found no sta's'cally different outcome comparing SAMe and other commonly used
an'depressant (imipramine or escitalopram).

LESSON 6: SUPPLEMENT - DRUG INTERACTIONS

Drug interac?ons can be:

• Alter ADME (Pharmacokine'c)
• Where drug affects ac'on or effect of other drugs (Pharmacodynamic)

Cytochrome P450
• Superfamily of enzymes that func'on as monooxygenases (>300,000)
o Oxidize steroids, faUy acids, and xenobio'cs
o Metabolize thousands of endogenous and exogenous compounds
o Account for ~75% of total drug metabolism
o Some metabolize only one (or a few substrates), others mul'ple
o Present in most 'ssues of the body
o Metabolism principally in the liver
o Human genome project has iden'fied 57 human genes coding for P450 enzymes
o Not just metabolism – some are bioac'vated
• Major source of drug interac'ons – changes in enzyme ac'vity may affect metabolism and clearance of various drugs
• Many drugs increase or decrease the ac'vity of CYP isozymes either by enzyme induc'on or inhibi'on
o For example, an'-epilep'c drugs induce CYP1A2, CYP2C9, CYP2C19 & CYP3A4
• Naturally occurring products may also induce or inhibit CYP ac'vity (e.g., grapefruit inhibits CYP3A4; tobacco smoking
induces CYP1A2)

Examples of drug interac?ons by CYP enzyme subtype:

• CYP1A1: Curcumin, Hops, Kava
• CYP1A2: Curcumin, Chamomile, Echinacea, Hops (inducer), St. John’s Wort (inducer)
• CYP2B6: St. John’s Wort (inducer)
• CYP2C9: Chamomile, Kava (inhibitor), St. John’s Wort (inducer)
• CYP2C19: Kava (inhibitor), St. John’s Wort (inducer)
• CYP2D6: Valerian, Kava (inhibitor), Chamomile
• CYP3A4: Echinacea, Curcumin, Valerian, Chamomile, Hops (inducer), Kava (inhibits), St. John’s Wort

17
P-glycoprotein
• Important mediator of interac'ons
• Pumps many foreign substances out of cells
• Involved in the transport of drugs from different drug classes, including an'neoplas'c drugs, calcium channel blockers,
digoxin, and others
• Absorp?on: P-glycoprotein is found in the apical (luminal) membrane of the en're intes'ne from duodenum to rectum,
with a high expression in the enterocytes of the small intes'ne. It reduces the oral availability of drugs that are its
substrates
• Role in distribu?on: Once a drug has reached the systemic circula'on, P-glycoprotein further limits penetra'on into a
number of sensi've 'ssues including BBB.
• Elimina?on is expressed in the luminal membrane of proximal tubule cells in the kidneys. P-glycoprotein pumps drugs
into the urine.
• The pharmacokine'cs of a drug may be altered when co-administered with compounds that inhibit or induce P-
glycoprotein
o Inhibitors include clarithromycin, erythromycin, ritonavir, and verapamil
o Inducers include rifampicin and St. John’s Wort

Herbal Supplements with Poten?al for Drug Interac?ons:

• Black Cohosh, Garlic, Ginkgo Biloba, Ginseng (Asian & American), Goldenseal, St. John’s Wort

Products with Poten?ally Dangerous Interac?ons:

Bleeding: Risk with an'-platelet and/or an'-coagulants (e.g., Warfarin)
o Evening Primrose Oil: Possible an'coagulant
o Fenugreek: An'platelet ac'vity
o Fish oil: An'platelet ac'vity in high doses
o Garlic: An'platelet ac'vity
o Ginkgo: Inhibits platelet aggrega'on
o Ginger - An'platelet ac'vity
o Ginkgo is known to inhibit platelet aggrega'on, which could theore'cally increase bleeding risk, especially in
combina'on with an'platelet or an'coagulant drugs; some studies database suggested an increased risk of
bleeding with concurrent ginkgo and warfarin use

Garlic
• Promoted for cardiovascular condi'ons
• May decrease concentra'ons of drugs transported by P-glycoprotein
• May induce bleeding risk, especially when used with an'coagulants

Ginseng
• American Ginseng: Low poten'al for drug interac'ons
• Asian Ginseng: May induce CYP3A4, leading to interac'ons with many drugs

Goldenseal
• Promoted for colds, respiratory infec'ons, diges've issues
• May inhibit CYP3A4/5 and CYP2D6, leading to significant interac'ons with other drugs

Licorice
• Promoted for diges've issues, menopausal symptoms, infec'ons
• May cause hypokalemia, edema, hypertension, and heart problems
• Poten'al interac'ons with drugs affec'ng potassium levels

Black Cohosh
• Promoted for menopause and menstrual symptoms
• Possible liver damage has been reported in some cases
• May interact with cholesterol-lowering drugs and hepatotoxic medica'ons

CNS Depression & S?mula?on

• S?mulants: Addi've effects with an'depressants (e.g., Ma Huang, St. John’s Wort)
• Depressants: Addi've somnolence with CNS depressants (e.g., Valerian, Kava)

Serotonin Syndrome

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 • Toxic state caused by excess serotonin, leading to fatal effects
• Risk of serotonin syndrome when using serotonergic drugs in combina'on (e.g., St. John’s Wort with an'depressants)

St Johns Wort
* St. John's wort (Hypericum perforatum) has been shown in mul'ple human studies to be a potent inducer of CYP3A4 and
P-gp
o induc'on of enzymes of the cytochrome P450 family
§ Moderate risk with CYP1A2, CYP2C9,
§ Major risk with CYP3A4 substrates such as ima'nib, indinavir, tacrolimus, carbamazepine, phenytoin
(dec levels and effect)
o induc'on of intes'nal P-glycoprotein drug efflux transporter à decrease levels of substrates such as digoxin,
fexofenadine, irinotecan.
o The reduc'on of plasma concentra'ons of oral contracep'ves could cause mid-cycle bleeding. The use of
addi'onal contracep've measures due to a possible reduc'on in contracep've efficacy is recommended.
o Reduces sta'n levels by up to 28%
o Several cases of serotonergic effects aher concomitant use of St. John's wort prepara'ons with certain
an'depressants have been reported.
§ Increased risk of serotonin syndrome – amitriptyline, anidepressants, tramadol, pethidine, triptans,
o Increased bleeding risk with clopidogrel
* Clinical studies have shown reduc'ons in cyclosporine (Sandimmune), tacrolimus, an'coagulants, protease inhibitors,
irinotecan (Camptosar), theophylline, digoxin, venlafaxine, and oral contracep'ves.

It is strongly recommended to avoid concurrent use of St. John's wort with over-the-counter and prescrip'on medica'ons

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