Transcript Key Herbs and Nutrients for

Key Herbs and Nutrients
for Functional Hormone
Resistance
Kerry Bone
Co-Founder and Director R & D, MediHerb
Adjunct Associate Professor, University of New England
Rob Santich
MediHerb Clinical Support Consultant
Adjunct Lecturer, University of New England
What is Functional Hormone
Resistance?
• Functional hormone resistance occurs when the
endocrine gland produces adequate amounts of a
given hormone, but the target cells are unable to
utilise that hormone properly
• The consequences are either that the effect of this
hormone is reduced OR that the body responds by
producing more of the hormone to compensate
• Both types of response can lead to chronic health
problems
Topics for Today
• Today’s presentation will briefly examine functional
hormone resistance involving insulin (which is welldocumented) and the more controversial
phenomena of thyroid hormone and cortisol
resistance
• The role of key herbs and nutrients in helping to
correct resistance to these major hormones will be
explored
Insulin Resistance
• Insulin resistance is a curse of modern lifestyle that
can lead to metabolic syndrome and type 2
diabetes
• It has also been linked to a wide
variety of other diseases such as
breast and prostate cancer,
PCOS, Alzheimer’s disease, gout
and NASH (non-alcoholic
steatorrhoeic hepatitis)
Metabolic Syndrome
• Metabolic Syndrome or Metabolic Syndrome X is an
insulin-resistant state characterised by a cluster of
cardiovascular risk factors first proposed in 1988,
although alluded to in earlier literature
• These include various combinations of abdominal
obesity, glucose intolerance, hypertension and
atherogenic dyslipidaemia
• The dyslipidaemia includes elevated triglycerides,
low HDL cholesterol, elevated apolipoprotein B and
small LDL particles
Johnson LW et al. Mayo Clin Proc 2006; 81(12): 1615-1620
Abdominal Obesity
• Abdominal or central obesity (visceral adiposity) is
probably the most significant issue in metabolic
syndrome1,2
• It underlies the key metabolic change, which is
insulin resistance1
• “Insulin resistance syndrome” is in fact an
alternative name preferred by some scientists
1. Fulop T et al. Pathol Biol (Paris) 2006; 54(7): 375-386
2. Shen W et al. Obesity (Silver Spring) 2006; 14(4): 727-736
Metabolic Syndrome:
A Modern Epidemic
• The prevalence of metabolic syndrome has reached
alarming proportions
• For Australia the estimated prevalence is between
24 and 26%
• Metabolic syndrome is more prevalent with
increasing age, affecting about 50% of adults aged
60 years and over. It is also more common in men
• For the first time in decades, medical scientists are
proposing that the average life expectancy might
FALL in industrialised countries
Chew GT et al. MJA 2006; 185(8): 445-449
Lifestyle and Metabolic Syndrome
• It is acknowledged by all consensus
groups that metabolic syndrome is
linked to lack of physical activity
• Physical activity not only assists weight
loss, it also directly improves insulin
sensitivity
• The current recommendation of the US American
Heart Association for metabolic syndrome is at least
60 minutes of continuous or intermittent aerobic
activity a day. Resistance training is also
recommended
Grundy SM et al. Circulation 2005; 112: 2735-2752
Diet and Metabolic Syndrome
• Dietary Risk factors associated with
metabolic syndrome include a high red
meat intake, cereals with a high
glycaemic index and refined
carbohydrates1,2,3
• Intake of whole grains and fruit
and vegetables were protective1,2,3
• Glycaemic index (GI) and glycaemic
load (GL) intakes have been positively
correlated with the degree of insulin resistance3
1. Baxter AJ et al. Asia Pac J Clin Nutr 2006; 15(2): 134-142
2. Sahyoun NR et al. Am J Clin Nutr 2006; 83(1): 124-131
3. McKeown NM et al. Diabetes Care 2004; 27(2): 538-546
Key Herbs and Nutrients for Insulin
Resistance
• Coleus – for weight loss/fat loss
• Licorice – for fat loss
• Gymnema, St Mary’s Thistle, Korean
Ginseng and Fenugreek, Mg and Cr
for improving insulin sensitivity
• Gymnema, Grape Seed extract and
Green Tea for reducing the GI of
food intake (taken just before meals)
Coleus and Body Weight
• In a double blind clinical trial conducted in the USA,
30 overweight/obese male volunteers (BMI  25)
were randomised to receive Coleus extract
(containing 50 mg/day of forskolin) or placebo for a
period of 12 weeks
• Administration of Coleus resulted in a significant
decrease in fat mass and body fat. The reduction in
fat mass from baseline to after treatment with
Coleus was 4.5 kg
Godard MP et al. Obes Res 2005; 13(8): 1335-1343
Coleus and Body Weight
• There was also a trend toward a significant increase
for lean body mass in the Coleus group compared
with the placebo group
• The average change in weight for those treated
with Coleus was a loss of 0.07 kg in contrast to an
average gain of 1.57 kg for the placebo group
• This extensive trial also found that treatment with
Coleus significantly increased bone mass
Godard MP et al. Obes Res 2005; 13(8): 1335-1343
Coleus: What to Use?
• Extracts of Coleus standardised for their forskolin
should always be used
• In the weight loss trials a Coleus extract delivered a
daily dose of 50 mg forskolin
• This could be formulated as a tablet containing
around 4 g of Coleus root and around 18 mg of
forskolin taken 2-3 times a day
• This would also be the dose for the other uses of
Coleus
• In liquid form the dose of a 1:1 extract should be
4 mL 2-3 times a day
Bone K. Clinical Applications of Ayurvedic and Chinese Herbs. Phytotherapy Press, Warwick,
1996, p 103-107.
Licorice, Central Obesity
and Fat Loss
• Licorice is well documented to inhibit
the activity of 11 beta-HSD type 2.
This is responsible for its aldosteronelike side effects
• If it also inhibits the type 1 version of this enzyme it
could help fat loss by inhibiting the effect of cortisol
on adipose tissue
• Recently a group of Italian scientists found that
licorice for 2 months reduced body fat mass in 15
healthy volunteers without any change in calorie
intake. BMI did not change
Armanini D et al. J Endocrinal Invest 2003; 26(7): 646-650
Silymarin and Insulin Resistance
• A recent placebo-controlled clinical trial found that
Silymarin extract (200 mg TDS) for 4 months
exerted a beneficial effect on glycaemic profile in
relatively well-controlled patients with type 2
diabetes (on medication)
• There were significant reductions in
HbA1C (13%), fasting blood glucose
(15%), total cholesterol (12%), LDLcholesterol (11%) and triglycerides
(25%)
Huseini H et al. Phytother Res 2006; 20:1036-1039
Gymnema and Insulin Resistance
• The value of Gymnema in significantly reducing total
cholesterol, triglycerides and fasting plasma glucose
in type 2 diabetes was demonstrated in a long-term
clinical trial
• The authors suggested that Gymnema
had a restorative effect on the beta
cells of the pancreas
• However an alternative explanation
could be a long term favourable effect on insulin
resistance
• Gymnema is marketed in Japan for weight loss
Bone K. Clinical Applications of Ayurvedic and Chinese Herbs. Phytotherapy Press, Warwick,
1996, p 115 – 117.
Korean Ginseng and
Insulin Resistance
• In well-controlled type 2 diabetic
patients Korean Ginseng caused no
change in HbA1C or fasting plasma
glucose in a placebo-controlled
clinical trial
• However, fasting plasma insulin was significantly
reduced for Korean Ginseng (by 34%) whereas it
increased in the placebo group (by 10%)
Vuksan V et al. Nutr Metab Cardiovasc Dis 2008;18(1):46-56
Chromium and Insulin Resistance
• The role of chromium in regulating insulin action is
well known
• A recent review concluded that chromium
supplements can lower insulin resistance and reduce
some of the metabolic disturbances associated with
metabolic syndrome1
• Other clinical studies published since that review
support this conclusion2,3
1. [No authors listed] Diabetes Edu 2004; Suppl: 2-14
2. Vladeva S et al. Folia Med 2005; 47(3-4): 59-62
3. Lydic M et al. Fertil Steril 2006; 86(1): 243-246
Magnesium and Insulin Resistance
• Ca and Mg intake is protective for metabolic
syndrome
• A placebo-controlled clinical trial in type 2 diabetic
patients found that Mg improved insulin sensitivity
and metabolic controls1
• There were significant reductions in fasting glucose,
HbA1C and the insulin resistance index (HOMA-IR)
• Epidemiological evidence and clinical studies support
the value of Mg in diabetes and insulin resistance2
1. Rodrigues-Moran M et al. Diabetes Care 2003; 26(4): 1147-1152
2. Sales CH, Pedrosa Lde F. Clin Nutr 2006; 25(4): 554-562
The Thyroid: An Overview
• Thyroid function has a profound impact on overall
health via its modulation of:
 carbohydrate
 protein
 fat metabolism
 vitamin utilisation
 mitochondrial function
 digestive process
 muscle and nerve activity, blood flow, oxygen
utilization, hormone secretion, sexual and
reproductive health, and many other
physiological parameters
The HPT axis
Thyroid Hormone Cascade
Negative Feedback
TRH
(Hypothalamus)
TSH
(Ant. Pituitary)
T3 and T4
(Thyroid)
Thyroid Hormones
Levothyroxine (T4)
• Four iodine atoms per molecule
• A relatively inactive form that can be converted into
T3
• Produced exclusively by the thyroid gland
• Circulation half-life of 7 days
Triiodothyronine (T3)
• Three iodine atoms per molecule
• Eight times more biologically active than T4
• It is converted from T4 in the thyroid, brain, liver,
bloodstream and various other tissues of the body
• Circulation half-life of 1 day
Thyroid Hormone Resistance
• Many patients show clinical evidence of low thyroid
function (especially low body temperature) but have
normal laboratory tests for TSH, T3 and T4
• It has been recently proposed that this phenomenon
is due to thyroid hormone resistance (THR), similar
to insulin resistance1
• This is not to be confused with subclinical
hypothyroidism, which is medically defined as normal
T3 and T4, but mildly elevated TSH (less than 10.0
MIU/L, normal range typically given as 0.3 to 5.5),2
although the two issues could occur together
1. Sylver N. Townsend Letter for Doctors and Patients 2008; #305: 66-73
2. Fatourechi V. Mayo Clin Proc 2009; 84(1): 65-71
Thyroid Hormone Resistance
• Subclinical hypothyroidism is usually associated with
antithyroid antibodies but THR is not1
• Attributed causes of THR include mitochondrial
dysfunction and environmental toxins including
heavy metals, dioxins and pesticides that act as
endocrine disrupters2
• Adrenal and thyroid function are connected and
elevated cortisol can interfere with thyroid function
and possibly lead to THR3
1. Fatourechi V. Mayo Clin Proc 2009; 84(1): 65-71
2. Sylver N. Townsend Letter for Doctors and Patients 2008; #305: 66-73
3. Andrews C, Morgan M. A Nutritional Perspective 2006; #25: 1-4
Thyroid Hormone Resistance
• It has also been proposed that chronic infection,
chronic inflammation and hypercoagulation can
cause THR1
1. Garrison RL, Breeding PC. Medical Hypotheses 2003; 61(2): 182-189
Diagnosis of THR
• The most reliable method of diagnosis of THR is the
symptom picture coupled with a positive Barnes
Basal Temperature test
• A favourable response to thyroid treatment
confirms the diagnosis
• Signs to look out for include puffy face and lips,
thinning hair and outer eyebrows, swollen skin, lack
of alertness, cold extremities, weight gain and
tendency to chronic infections
• However, low thyroid function is the “great
imitator” that can mimic a vast number of medical
conditions
Barnes Basal
Temperature Test
• Basal temperatures are taken first thing in the
morning, when your body is completely at rest.
At night, before you go to bed, shake the
thermometer down and leave it on your bedside
table. In the morning, before getting out of bed
and with as little movement as possible, place the
thermometer under your arm
and leave it there for 10 minutes. Do
not drink alcohol the night before you
take your basal temperature
• Use a mercury basal thermometer
rather than a digital thermometer
Barnes Basal
Temperature Test
• Menstruating women must take their temperatures
on the 2nd, 3rd and 4th days of their periods only
• Non-menstruating women, women who have had
hysterectomies and men may take their
temperatures any time
• Temperatures below 36.6°C indicate hypothyroid
function and possible THR if hormone tests are
normal
Therapeutic Strategy for THR
• Herbs to boost thyroid function as a compensatory
measure: Bladderwrack, Withania, Bacopa, Coleus,
Olive Leaf
• Nutritional support with selenium, iodine, tyrosine,
zinc, B1, B2, B3, B5, C and E
• Herbs and nutritional support of detoxification
processes: Schisandra, Turmeric, Rosemary, Garlic,
St Mary’s Thistle, glutamine, glycine, taurine
• Herbs for adrenal support: Licorice and Rehmannia
Key Herbs for THR
Bladderwrack (Fucus vesiculosus)
• A shore-dwelling seaweed not to be
confused with the deep-sea kelp
(Laminaria spp.)
• Contains free and organically-bound iodine
• Experimental studies in the early 19th century found
oral doses stimulated the thyroid gland
• Contains polysaccharides which bind to
heavy metals such as Pb, Hg and Cd,
reducing toxic load
• Traditionally used to help weight loss
Bone K. A Clinical Guide to Blending Liquid Herbs: Herbal Formulations
for the Individual Patient, 1e, Churchill Livingstone, St. Louis, 2003: p.103-105.
Key Herbs for THR
Ashwaganda (Withania somnifera)
• Significantly boosted T4 (up to
111%) in experimental models1,2
• T3 was also increased, but to a
lesser extent1
• Its adaptogenic and tonic effects will also boost
depleted energy levels
1. Panda S, Kar A. J Pharm Pharmacol 1998; 50: 1065-1068
2. Panda S, Kar A. J Ethnopharmacol 1999; 67: 233-239
Key Herbs for Hypothyroidism
Coleus
• The key component forskolin catalyses the
production of cAMP
• This potentiates the intracellular effects of many
hormones, including TSH
• The craze for Coleus as a weight loss agent has led
to a worldwide shortage
Bone K. Clinical Applications of Ayurvedic and Chinese Herbs. Phytotherapy Press,
Warwick, 1996, p 104.
Case History
• A 41-year-old female patient (BMI 38) presented in
June 2009 with signs and symptoms of weight gain,
“foggy” thinking, dry skin and hair, variable appetite
and lack of energy. Her waist:hip ratio was 0.85
• She also experienced anovulatory cycles for the past
6 months. PCOS was suspected
• The patient had been diagnosed as “hypothyroid”
by another practitioner and since then began
charting her basal body temperature, which was
generally low
• TSH was 3.8 and previous natural treatment had
not helped greatly. THR was suspected as the likely
diagnosis
Case History
• The following treatments were progressively
prescribed:
Liquid Formulation
Paeonia lactiflora
Licorice (high in glycyrrhizin)
Chaste tree
Fennel
Olive leaf
Dosage: 5 mL twice a day
1.2
1:1
1:2
1:2
1:2
40
20
15
15
20
110
mL
mL
mL
mL
mL
mL
Case History
• ThyroCo tablets (contain Bladderwrack, Withania,
Bacopa) 4 twice a day
• ThyAdren Support tablets (contain Rehmannia,
tyrosine, C, B1, B2, B3, E, Zn, Se, I etc) 1 twice a
day
• Coleus Forte tablets (containing 18.7 mg forskolin)
at 2 to 3 per day later replaced the ThyAdren
Support tablets (Nov 09) to further improve weight
loss and waist:hip ratio and support thyroid function
Case History
Outcomes
• By August 09 more energy was present and the
patient was coping better with the day and had
improved appetite
• By Nov 09 ovulation had returned and her waist:hip
ratio was down to 0.79
• The following temperature chart illustrates the
progressive improvement in basal body temperature
• Treatment is ongoing
Case History
2009 Cycle Chart
36.7
36.6
36.5
36.4
36.3
36.2
Temperature
36.1
June
36
35.9
35.8
July
35.7
35.6
35.5
Sept
35.4
35.3
35.2
Oct
35.1
35
1
2
3
4
5
6
7
8
9
10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31
Day of the month
Nov
Dietary Considerations for THR
• Some foods contain phytochemicals that can
compromise thyroid function via a variety of
mechanisms
• While they are a normal part of a healthy diet, they
are best avoided or minimised in THR
• These foods include linseeds, Brassica species
(cabbage, cauliflower, broccoli etc), garlic, walnuts
and soya
Bone K. Professional Monitor 1992 Dec; No. 3; pp 3-4
www.mediherb.com.au/pdf/tc_256c.pdf
Functional Cortisol Resistance
• The best example of chronic hyperactivation of the
stress system (both the HPA axis and the
noradrenergic system), probably due to a functional
cortisol resistance, is melancholic depression
• Hypersecretion of CRH from the hypothalamus has
been shown in depression, with associated
increases in ACTH and plasma cortisol
• This hypersecretion of CRH is thought to be due to
an impaired sensitivity of glucocorticoid receptors in
the cerebral cortex, hypothalamus and pituitary,
which impedes the normal negative feedback effect
of cortisol
Tsigos C, Chrousos GP. J Psychosom Res 2002; 53(4): 865-871
Functional Cortisol Resistance
• The higher amounts of cortisol in melancholic
depression has damaging effects leading to
osteoporosis, metabolic syndrome, chronic
infections and cancers
• When not treated these patients have a reduced life
expectancy of 15 to 20 years after excluding suicide
• Other conditions possibly associated with functional
cortisol resistance (FCR) include anorexia nervosa,
OCD, metabolic syndrome, chronic alcoholism and
overtraining syndrome
Tsigos C, Chrousos GP. J Psychosom Res 2002; 53(4): 865-871
Rhodiola, FCR and Depression
• In a randomised, double blind, placebo-controlled
model, male and female patients aged 18 to 70
years with Hamilton Rating Scale for Depression
(HAMD) scores of 21 to 31 were divided into 3
groups
• Over 6 weeks Group A (n = 31) received 340 mg of
Rhodiola extract (equivalent to about 1.7 g of root)
per day, Group B (n = 29) received 680 mg/day of
extract and Group C (n = 29) were assigned a
matching placebo
Darbinyan V, Aslanyan G, Amroyan E et al. Nord J Psychiatry 2007; 61(5): 343-348
Rhodiola, FCR and Depression
• Both the HAMD and the Beck Depression Inventory
(BDI) were used to assess treatment outcomes at 6
weeks
• The BDI is a series of questions developed to
measure the intensity, severity and depth of
depression
• In terms of overall depression, there were highly
significant reductions (p<0.0001) in both the HAMD
and BDI scores 6 weeks after Rhodiola treatment
that was not evident in the placebo group
Darbinyan V, Aslanyan G, Amroyan E et al. Nord J Psychiatry 2007; 61(5): 343-348
Rhodiola, FCR and Depression
• The average HAMD score in Groups A and B fell
from around 25 to around 18 for both groups,
indicating that a dose-response effect was not seen
for this outcome
• In contrast, a dose-response relationship was
observed for the BDI scale, with values falling from
around 11 to about 8 in Group A and from about 11
to 5 in Group B
Darbinyan V, Aslanyan G, Amroyan E et al. Nord J Psychiatry 2007; 61(5): 343-348
Rhodiola, FCR and Depression
• Stress-activated protein kinase (SAPK, also known
as JNK) inhibits the sensitivity of glucocorticoid
receptors to cortisol. In an experimental model,
both Rhodiola extract and salidroside decreased the
release of SPK/JNK and cortisone in response to
stress
• Hence the authors postulated that Rhodiola inhibits
the stress-induced activation of SAPK/JNK in
depressed patients and thereby restores the
impaired sensitivity of glucocorticoid receptors to
cortisol
• Rhodiola also lowered awakening cortisol levels in
patients with chronic stress and fatigue1
Olsson EM, von Schéele B, Panossian AG. Planta Med 2009; 75(2): 105-112
Key Herbs for FCR
• Adaptogens fine tune the stress response:
 Siberian Ginseng
 Withania
 Rhodiola
• Adrenal tonic or restorative
herbs support and restore
the adrenal cortex
 Licorice
 Rehmannia
Hormonal Inter-relationships
• The three key hormones discussed today exhibit
functional relationships with each other
• For example, exercise and weight loss-induced
improvements in insulin resistance were blunted by
poor thyroid status (subclinical hypothyroidism)1
• The relationship between excess cortisol and insulin
resistance or impaired thyroid function have already
been discussed
• Hence treatment may sometimes be required for
more than just the one functional hormone
resistance in order to achieve the desired clinical
outcome
1. Amati F et al. Med Sci Sports Exerc 2009 41(2): 265-269
Conclusions
• Insulin resistance is a common form of hormone
resistance well-described in the medical literature
• However, there is an emerging body of evidence to
suggest that functional resistance to other vital
hormones can also occur, notably thyroid hormones
and cortisol
• These can manifest together in the one patient and
exhibit functional inter-relationships
• Herbs and a few vital nutrients have a valuable role
to play in helping patients to overcome this modern
phenomenon of functional hormone resistance