Download Xymogen Powerpoint - Freedom Practice Coaching

The Functional Matrix
of Stress Management
Cheryl Burdette, ND
Xymogen Director of
Research Outreach & BOA
Dunwoody Labs
Progressive Medical
Disclaimer
• The information that follows represents XYMOGEN’s
choices for presentation of studies, comments, and/or
opinions. The statements have not been evaluated by
the FDA. The products are not intended to diagnose,
treat, cure, or prevent any disease.
• It is assumed that the practitioner will investigate the
topic further and not use this presentation as a sole
source of information from which to derive an
individualized patient protocol.
Disclosure
• I am not a XYMOGEN employee.
• I am a XYMOGEN customer.
• I will receive compensation from
XYMOGEN for this presentation.
• I am a XYMOGEN shareholder.
• I am a physician, wife, mother (two
human, two dogs) and a fellow human
being on this planet.
Stress and occurrence
• Clinically relevant distress is present in 40% to 50%
of cancer outpatients. (i, ii)
• Chronic stress predicts the occurrence of coronary
heart disease (CHD).(iii)
• Employees who experience work-related stress and
individuals who are socially isolated or lonely have an
increased risk of a first CHD event.
• A history of stressful life events is correlated
greater incidence of metabolic syndrome (in men),
especially in those men with elevated cortisol
(independent of BMI and age). (iv)
(i) Hoffman et al. Screening for distress in cancer patients: the NCCN rapid-screening measure. Psychooncology,
2004;13:792.
(ii) Jacobsen et al. Screening for psychological distress in ambulatory cancer patients. Cancer, 2005;103:1494.
(iii) Steptoe A, Kivimäki M. Stress and cardiovascular disease. Nat Rev Cardiol. 2012 Apr 3;9(6):360-70.
(iv) Fabre B, et al. Relationship between cortisol, life events and metabolic syndrome in men.Stress. 2012 Apr 18.
Stress can disrupt circadian rhythms and
favor tumor initiation and progression
• Night-time shift work, a condition that is known to
disrupt circadian rhythms, is a risk factor for breast
and colorectal cancer.
• In mouse studies, tumor progression and mortality
are dramatically accelerated after elimination of
circadian rhythms by manipulation of light–dark
cycles.
• Two clinical studies have also shown that the status
of circadian cycles, such as cortisol or the 24-hourrest–
activity cycle, can predict long-term cancer
survival. (i)
Antoni MH, et al. The influence of bio-behavioural factors on
tumour biology: pathways and mechanisms. Nat Rev Cancer. 2006;6
(3):240-8.
Severe Adrenal Stress
• Women with metastatic breast cancer
had significantly flatter diurnal cortisol
rhythms as compared with healthy
controls. (i)
(i) Abercrombie HC, et al. Flattened cortisol rhythms in
metastatic breast cancer patients.
Psychoneuroendocrinology. 2004;29:1082–1092.
When To Suspect Adrenal Stress
•
•
•
•
•
•
•
Fatigue
Hypoglycemic Symptoms
Menopausal Symptoms
Brain fog
Worse under stress
Insomnia
Weight Gain
This affects mortality
Patients with metastatic breast cancer whose
diurnal cortisol rhythms were flattened or
abnormal had earlier mortality. (P =.0036) (i)
◦ N = 104 women with metastatic breast cancer
followed for 7 years
◦ Flattened cortisol rhythm was associated with
suppression of NK cell count and NK function may
be a mediator or a marker of more rapid disease
progression.
Sephton SE, et al. Diurnal cortisol rhythm as a predictor of breast
cancer survival. J Natl Cancer Inst. 2000;92:994–1000.
Pessimism is a factor
• Clinical and epidemiological studies over the last 30 years
have identified psychosocial factors especially stress,
chronic depression and feelings of isolation as risk factors
for cancer progression.
• Chronicity of negative affect, as manifested by depressed
mood or hopelessness/pessimism, appears to have
stronger relationships with outcomes than do stressful
events. (i)
• This suggests that sustained activation of
negative moods may provide the strongest links
to cancer progression.
(i) Moreno-Smith M, et al. Impact of stress on cancer metastasis. Future Oncol. 2010 Dec;6
(12):1863-81.
In summary, pessimism was associated with higher levels of markers
for systemic inflammation in a large, healthy, diverse population. These
associations were independent of depression and cynical distrust.
Common Markers That Reveal Stress
Patterns
• Glucose-- < 70 if fasting, adrenal fatigue
• Glucose—climbing, gluconeogenesis due
to stress
• Sodium and Potassium: both less than
midrange with no dietary reason
• Low Reproductive Hormones
• High Reverse T3
Stress and Pathology
• Stress increases growth and metastatic
spread of tumors in animal models (i)
• Stress reduces host resistance to breast
cancer recurrence (ii)
• Stress increases inflammation and alters
glucose metabolism
(i) Ben-Eliyahu S, et al. Stress increases metastatic spread of a
mammary tumor in rats: evidence for mediation by the immune
system. Brain Behav Immun. 1991;5(2):193-205.
(ii) Palesh O, et al. Stress history and breast cancer
Contributing stress hormones
• CRF
• Cortisol
• Epinephrine
• Norepinephrine
Vitamin C
G-Coupling
Increased mitosis with stress
• The signals are transduced to the nucleus, where
transcription factors regulate gene expression, and to
the cytoskeleton to enable the spatial
organization of signaling complexes.
• Scaffolds provide a mobile 'toolbox' of protein
kinases, phosphatases and adaptor molecules that
add to the dynamic character of the responses.
• Associations with microtubules, actin-filament
networks and mitotic spindles are examples of the
spatial organization of G-protein signaling within the
cell.
Stress hormones turn on the
molecular switch
•
•
•
These receptors are coupled to G-proteins, and act as molecular switches to
control downstream pathways. There are 9 sub-types, five αADRs and four
ßADRs. (i)
Certain ADRs activate stimulatory G-protein pathways which mediate
activation of the cAMP dependent protein kinase pathways that result in
growth and migration of cells.
ßADRs are present on breast and ovarian cancer cells. α ADRs have been
found to exert proliferative effects on prostate and pituitary cancer cells. (ii)
•
Cortisol and its metabolite cortisone has also been shown to
stimulate the growth of prostate cancer cells in the absence
of androgens and to increase the secretion of prostate
specific
antigen.
(i) Moreno-Smith M, et al. Impact of stress on cancer metastasis.
Future Oncol. 2010;6(12):1863-81.
(ii) Zhao XY, et al. Glucocorticoids can promote androgen-independent
growth of prostate cancer cells throug
Stress and VEGF
•
•
•
•
Resveratin
NE has been shown to upregulate VEGF in adipose tissue
through the ßADR–cAMP–PKA pathway.
This pathway has been demonstrated in ovarian cancer cells
and multiple myeloma cells.
Clinical studies have shown links between higher levels of
social support and lower levels of VEGF levels in serum (i) and
in tumor tissues (ii) in ovarian cancer patients.
In addition, depression and quality of life have been related to
VEGF in
colorectal cancer. (iii)
(i) Lutgendorf SK, et al. Vascular endothelial growth factor and social
support in patients with ovarian carcinoma.Cancer. 2002;95(4):808-15.
(ii) Lutgendorf SK, et al. Biobehavioral influences on matrix
metalloproteinase expression in ovarian carcinoma. Clin Cancer Res.
2008;14(21):6839-46.
(iii) Sharma A. et al. Vascular endothelial growth factor and psychosocial
factors in colorectal cancer. Psychooncology. 2008;17(1):66-73.
NE increases IL-6
Ig26
• NE binds to ßADR and increases IL-6 gene
transcription.
• Other proliferative, angiogenic genes are
also upregulated including VEGF and IL-8.
• Under the influence of NE, solid tumor
cells’ secretion of high levels of IL-6, which
promotes metastasis by increasing
proliferation, angiogenesis, attachment and
invasion, may increase. (i)
(i) Nilsson MB, et al. Interleukin-6, secreted by human ovarian carcinoma cells, is a potent proangiogenic
cytokine. Cancer Res. 2005;65(23):10794-800.
Matrix Metalloproteinase and stress
CurcuPlex
• NE and E can increase MMP production by tumor cells.
(i)
• NE and E also act as chemoattractants to induce cell
migration.
• Stress levels of NE increased the in vitro invasiveness of
ovarian cancer cells by 8% to 198%. (ii)
• E also induced significant increases in invasion of ovarian
cancer cells ranging from 64 to 76%.
• NE and E significantly increase production of MMP-2 and
MMP-9 by ovarian cancer cells through activation of the
ßADR pathway. This has also been demonstrated in colon
and head and neck cancers.
(i) Yang EV, et al. Stress-related modulation of matrix metalloproteinase
expression. J Neuroimmunol. 2002;133(1-2):144-50.
(ii) Sood AK, et al. Stress hormone-mediated invasion of ovarian cancer cells.
Clin Cancer Res. 2006;12(2):369-75.
(i) Rangarajan S et al. Cyclic AMP induces integrin-mediated cell
adhesion through Epac and Rap1 upon stimulation of the beta
2-adrenergic receptor. J Cell Biol. 2003;160(4):487-93.
Cell adhesion to the proteins of the extracellular
matrix is mediated in part by a group of
heterodimeric transmembrane proteins called
integrins. (i)
• NE increases cAMP and cAMP cell adhesion in many cell types.
• Thus, stress hormones may
promote cell matrix attachment
of cancer cells.
Glucocorticoids may effect chemo
• While glucocorticoid hormones induce apoptosis in
lymphocytes and lymphoblastic leukemia cells, their
effects are different in solid tumor cells.
• GCs activate survival genes and downregulate apoptotic
pathways. These actions protect solid tumor cancer cells
from the effects of chemotherapy. (i)
• Clinically, GCs are frequently administered with cytotoxic
agents to reduce the risk of emesis and other potential
acute toxicities. However, concerns have been raised
about this combination since some studies suggest that
GCs may reduce the efficacy of chemotherapy. (ii)
CortiSolv
(i) Distelhorst CW. Recent insights into the mechanism of glucocorticosteroid-induced apoptosis. Cell Death
Differ. 2002;9(1):6-19.
(ii) Zhang C, et al. Corticosteroid co-treatment induces resistance to chemotherapy in surgical resections,
xenografts
Stress-induced cortisol (C) binding to the glucocorticoid receptor (GR) causes
translocation of the GR to the cell nucleus and changes in the expression of
apoptotic and DNA repair genes.
Antonova L, et al. Stress and breast cancer: from epidemiology to molecular biology. Breast Cancer Res. 2011;13(2): 208.
Prolonged presence of cortisol, such as in periods of stress, leads to an
increase in both the proliferative and antiapoptotic effects of the receptor,
creating transformation-promoting intracellular conditions.
Oncoplex
Dopamine as a therapeutic target
•
•
AdrenaMax
•
•
•
Dopamine, the third member of the catecholamine family and
precursor in the synthesis of NE and E, is one of the major
neurotransmitters in the brain and also has important roles in
the periphery.
DA has the opposite effect compared with NE and E with
regard to the effects on tumor angiogenesis, growth and
development of ascites
DA levels are increased in the brain during acute stress. By
contrast, under chronic stress, there is decreased release of
DA. (i)
DA treatment can counteract the stimulatory effects of NE on
tumor growth in two ovarian stress cancer mice models. (ii)
These findings implicate DA as a potential therapeutic strategy
for blocking the deleterious effects of chronic stress.
(i) Imperato A, et al. Repeated stressful experiences differently affect limbic
dopamine release during and following stress. Brain Res. 1992;577(2):194-9.
(ii) Moreno-Smith M, et al. Dopamine blocks stress-mediated tumor growth in
ovarian carcinoma; Presented at: 100th Annual Meeting of American Association
for Cancer Resesarch; Denver, CL, USA. 18–22 April 2009.
Mast cells and stress
• Stress activates CRH which, in turn, activates
the HPA axis and mast cells.
• Mast cells can accumulate around tumors in
response to tumor-derived peptides
• Mast cells secrete numerous vasoactive,
inflammatory
• and growth promoting mediators including IL6, IL-8, and VEGF (and CRF selectively
stimulates secretion of VEGF) and promote:
– Angiogenesis
– Immune suppression
– Tumor proliferation
– Metastasis
Mast Cell Degranulation
•
•
•
•
OmegaPure
AllerDHQ
HistDAO
Treat The Stress…
BBB and stress
•
•
•
•
•
Mast cells encircle endothelial cells and pericytes making up the
BBB and have been proposed to act as “gate keepers” of the BBB
(i)
Acute stress can disrupt the BBB through mast cell activation by
corticotropin releasing hormone (CRH).
Functional CRH-receptors (CRH-R) are expressed on human mast
cells (ii) and on brain vessels (iii)
Human mast cells not only respond to, but also synthesize and
secrete CRH. (iv)
CRH-R are expressed by a number of human cancers (v)
IgY26
(i) Theoharides, T.C. Mast cells: the immune gate to the brain. Life Sci. 1990;46:607–617.
(ii) Chrousos, G.P. The hypothalamic-pituitary-adrenal axis and immune-mediated inflammation. N. Engl. J. Med.
1995;332:1351–1362.
(iii) Theoharides, T and Cochrane D. Critical role of mast cells in inflammatory diseases and the effect of acute stress.
J.Neuroimmunol. 2004;146: 1–12.
(iv) Esposito, P. et al. Corticotropinreleasing factor (CRF) can directly affect brain microvessel endothelial cells. Brain Res.
2003;968:192–198.
(v) Reubi, J. et al. Expression of CRF1 and CRF2 receptors in human cancers. J. Clin. Endocrinol. Metab. 2003;88:3312–
3320.
Stress increases brain mets
• Stress appears to permit brain metastases, and it also
activates brain mast cells that disrupt the BBB.
• Mast cells are involved in stress-induced inflammation
(i) and could be critical in increasing BBB permeability
and allowing cancer cell entry into the brain.
• Acute stress permits brain metastases of mammary
adenocarcinoma in mice.
• Evidence suggests that chronic inflammation with
increased mast cells accumulation and activation around
tumors could promote tumor growth and BBB
permeability.
Ig26
• (i) Theoharides, T.C., Cochrane, D.E., Critical role of mast
cells in inflammatory diseases and the effect of acute
stress. J. Neuroimmunol. 2004;146:1–12.
Immune/Auto-Immune shift due to
Stress
•
•
•
•
Vitamin D
IgY26
Acute/short-term fight or flight stress can enhance innate immunity.
Short-term stress enhances cellular immunity and increases early resistance
to squamous cell carcinoma (i)
Chronic elevation of stress hormones (catecholamines and GCs): Enhance
Th2 immunity by shifting immunity from predominantly Th1 to Th2 cells
which enables tumor cells to evade immune surveillance. (ii)
Increase regulatory or suppressor T-cell numbers within tumors and in the
circulation trigger lymphocyte apoptosis via increased expression of death
ligand, Fas, resulting in lymphocyte reduction that, in turn, might result in
an increase in the incidence of oncogenic viral infections and DNA damage
(iii)
(i) Dhabhar FS, et al. Short-term stress enhances cellular immunity and increases
early resistance to squamous cell carcinoma. Brain Behav. Immun. 2010;24(1):127–
137.
(ii) Calcagni E, Elenkov I. Stress system activity, innate and T helper cytokines, and
susceptibility to immune-related diseases. Ann. NY Acad. Sci. 2006;1069:62–76.
(iii) Shi Y. et al. Stressed to death: implication of lymphocyte apoptosis for
psychoneuroimmunology.Brain Behav Immun. 2003;17 Suppl 1:S18-26.
Stress decreases NK cells
•
Distress measured by self-report was correlated with low NK-cell cyto-toxicity in tumorinfiltrating lymphocytes from human ovarian cancers. (i)
•
Low peripheral NK-cell counts are prognostic for early breast cancer mortality, and
reduced NK-cell cytotoxicity is predictive of a poor clinical outcome in patients with
breast carcinoma. (ii)
•
Positive psycho-social factors such as social support , spiritual activities, and humor
have each been associated with increased levels of NK-cell cytotoxicity in patients with
breast (iii) and ovarian cancer.
CortiSolv
(i) Lutgendorf SK, et al. Social support, psychological distress, and natural killer cell activity in
ovarian cancer. J Clin Oncol. 2005;23:7106–7113.
(ii) Sephton SE, et al. Diurnal cortisol rhythm as a predictor of breast cancer survival. J Natl
Cancer Inst. 2000;92:994–1000.
(iii) Levy SM, et al. Perceived social support and tumor estrogen/progesterone receptor status
as predictors of natural killer cell activity in breast cancer patients. Psychosom Med.
1990;52:73–85.
Telomeres
Telomeres are essential for
Chromosomal stability
(protect the ends of the
chromosomes).
‣ The steady shrinking
of telomeres with
each mitosis
imposes a finite life
span on cells (about
70 divisions for
mammalian cells).
‣ Normal cells have
minimal telomerase
Short telomeres are predictive for
malignant cells
• While telomere elongation is a common molecular
feature of advanced malignancies, short telomeres and
concurrent chromosomal instability contribute to
malignant cell transformation.
• Prospective population study of 787 patients without
evidence of cancer were followed for 10 years. (i)
• Baseline telomere length was substantially shorter in
participants with incident cancer (mean telomere length,
1.12; 95% CI, 1.01-1.23) than in those who remained
free of cancer (mean telomere length, 1.53 [95% CI,
1.47-1.59]; P<001).
• Tumors with a high fatality rate tended to exhibit more
prominent relationships with telomere length and
tumors with a more favorable prognosis showed modest
or no associations.
(i) Willeit P, et al. Telomere length and risk of incident cancer and cancer
mortality.JAMA. 2010;304(1):69-75.
Stress and telomere length
• ‣ High perceived stress (with increased urinary
output of stress associated Epi. and Norepi.) (i)
• ‣ Full-time work and longer history of full time
• work (related to stress) (ii)
• ‣ Sleep deprivation shortens telomeres
• ‣ Oxidative stress shortens telomeres: (iii)
• o Obesity
• o Cigarette smoking
(i) Parks CG, et al. Telomere length, current perceived stress, and
urinary stress hormones in women. Cancer Epidemiol Biomarkers Prev.
2009 Feb;18(2):551-60.
(ii) Parks CG, et al. Employment and work schedule are related to
telomere length in women. Occup Environ Med.2011;68(8):582-9.
(iii) Valdes AM, et al. Obesity, cigarette smoking, and telomere length
in women. Lancet. 2005 Aug 20-26;366(9486):662-4.
Child abuse and telomeres
Childhood adverse life events that provoke
anxiety and distress are directly correlated
with telomere length as an adult.
◦ Telomeres protect and stabilize
chromosomes, reducing the risk of
aneuploidy, methylation disruptions and
mutations.
(i) Kananen L, et al. Childhood adversities are associated
with
shorter telomere length at adult age both in individuals with
an
anxiety disorder and controls. PLoS One. 2010 May 25;5
(5):e10826.
Higher pessimism is associated with shorter TL in leukocytes.
Pessimism is also associated with higher basal levels of IL-6, an
indicator of systemic inflammation (and oxidative stress). (i)
(i) O’Donovan A, et al. Pessimism
correlates with leukocyte telomere
shortness and elevated interleukin-6
in post-menopausal women. Brain
Behav Immun. 2009; 23(4): 446–
449.
Stress Patterns
Five stress-busting ingredients*
Cortisolv Supplement Facts Serving Size: 1 Capsule
Amount Per Serving
%Daily Value
Relora†® (a proprietary blend
of a patented†† extract from
Magnolia officinalis bark and a
proprietary extract from
Phellodendron amurense bark)
250 mg
**
Sensoril® Ashwagandha
(Withania somnifera) Root and
Leaf Extract (10%
withanolides)
150 mg
**
Suntheanine® L-Theanine
100 mg
**
Banaba Leaf Extract
(Lagerstroemia speciosa)(1%
corosolic acid)
50 mg
**
Maral Extract (Rhaponticum
carthamoides)(root)
50 mg
**
Adrenal Treatments
• Tired But Wired: CortiSolv, RelaxMax
• Tired and Wired ++ : CortiSolv,
RelaxMax, CortiCare
• Tired And Tired: Adrenal Manager and
CortiCare
• Tired and Sick: Adrenal Essence
(Cordyceps), CortiSolv
• Tired and Depressed: AdrenaMax
(Tyrosine)
RelaxMax
CortiCare
Adrenal Treatments
• Tired But Wired: CortiSolv, RelaxMax
• Tired and Wired ++ : CortiSolv,
RelaxMax, CortiCare
• Tired And Tired: Adrenal Manager and
CortiCare
• Tired and Sick: Adrenal Essence
(Cordyceps), CortiSolv
• Tired and Depressed: AdrenaMax
(Tyrosine)
Adrenal Manager
Adrenal Treatments
• Tired But Wired: CortiSolv, RelaxMax
• Tired and Wired ++ : CortiSolv,
RelaxMax, CortiCare
• Tired And Tired: Adrenal Manager and
CortiCare
• Tired and Sick: Adrenal Essence
(Cordyceps), CortiSolv
• Tired and Depressed: AdrenaMax
(Tyrosine)
Cordyceps
AdrenaMax
Normal Adrenal Function
Early Adrenal Fatigue
Early Adrenal Fatigue
Early Adrenal Fatigue
• CortiCare-2, 2x a day for three months
or until improvement
• CortiSolv-1-2, 2x a d
Moderate Adrenal Fatigue
Moderate Adrenal Fatigue
Moderate Adrenal Fatigue
• CortiCare-2, 2 or 3x a day
• AdrenaMax-2 in the a.m.
Severe Adrenal fatigue
Severe Adrenal Fatigue
Severe/The Whole Kitchen Sink
• CortiCare-2, 2x a day
• AdrenaMax-2 in the am and 2 in the
afternoon
• CortiSolv-2 in the pm
Insomnia
Insomniac Adrenal Fatigue
Insomnia Pattern
•
•
•
•
Sedalin-2 before bed
Melatonin CR-one before bed
RelaxMax-1 scoop before bed
I5
Sedalin
Melatonin CR
High A.M. Cortisol
What is The Night Time Stress
• Apnea-obstructive
• Night Terrors-5-HTP CR, Melatonin CR,
OptiMg 125 or OptiMag Neuro
5-HTP CR
GABA/Theanine Cream and
Magnesium Cream (MagnaSol)
Immunoglobulins and Stress
• Immunoglobulins may represent a valid stress marker since they react
slowly and over a long time. They may, therefore, represent an
integrated function of sustained activation over prolonged time. Low
levels of immunoglobulins have been found to relate to personality
and subjectively experienced stress levels in a population subjected to
long lasting work load with feelings of incompetence and insufficiency.
No such relationships were found in a population which was subjected
only to brief exposures to intense fear. The psychological factors in our
own study explained up to 30% of the variance in the
immunoglobulins and complements, even if all levels were within the
normal range. The relationship between these findings and pathology
has not been proven, but is a tempting opening for psychosomatic
research and for identification of valid stress markers.
Breakdown in Human Adaptation to ‘Stress’
pp 681-690 Immunoglobulins as Stress Markers? H. Ursin
Stress is a Major Contributor To Leaky
Gut!!!
GL: 10/16/1955
• CC: fatigue and stomach issues
• Standard blood work: elevated
monocytes
Dunwoody Labs Food Sensitivity Report
We have reviewed scientific evidence that
appears to demonstrate that probiotics may be
used to treat allergies.
•It’s important to remember that dietary
supplements CANNOT mitigate diseases
or replace drugs.
•
However, XYMOGEN products
CAN give your patients their best chance
to stay healthier longer*
* These statements have not been evaluated by the US Food and Drug Administration. These products are not
intended to diagnose, treat, cure , or prevent any disease.
Treatment
• OptiFiber SCFA: supporting fiber
• Mito Kit: A combination arginine, alpha lipoic acid
and resveratrol for mitochondrial support
• S-acetyl glutathione: An orally absorbed form of
glutathione
• OptiMag 125
• OptiMetaboliX: Functional food for blood sugar
regulation
• IgG 2000 plus: Immunoglobulins in combination
with probiotics
• CortiCare: A combination of nutrients for adrenal
function (B5, B6, Vitamin C, carnitine)
* These statements have not been evaluated by the US Food and Drug Administration. These products are not intended to diagnose, treat,
cure , or prevent any disease.
Dunwoody Labs Food Sensitivity Report
Complaint
Number Of Patients
Reporting For Initial
Test
Number Of Patients
Reporting For Second
Test
Memory/Concentration
22
3
Anxiety/Mood/Depression
20
3
Bloating/Stomach Pain
18
2
Fatigue
18
4
Joint Pain / Stiffness / Swelling
13
1
Muscle Aches
13
1
Craving Sugar
12
2
Sleeplessness/Insomnia
12
0
Lightheaded/Dizzy
11
2
Allergies/Sinus
9
2
Cold Intolerance
Inability to lose weight
9
9
3
2
IgY26 and IgG 2000 CWP
Follow-up
•
•
•
•
•
•
•
Energy 7/10
Feels much better
Less hair loss
BM: 2 a day
Gas/Bloating-Resolved
H. Pylori-negative
Monocytes – in normal range
(Other treatment included working on treatment of parasite, identified
with stool culture and concomitant high sIgA.)
OptiGHI
ProbioMax
HistDAO
Introducing
CortiSolv™
Natural Stress Buster*
*These statements have not been evaluated by the Food and Drug Administration. This product is not
intended to diagnose, treat, cure, or prevent any disease.
Symptoms of everyday stress may
reduce quality of life
• Headache
• Digestive complaints—Major cause of leaky
gut
• Fatigue
• Muscle/Joint aches and pains
• Sleep difficulties
• Skin issues
• Dry mouth
• Clenching jaw/grinding teeth
• Irritability
Managing Stress
• Healthy eating pattern and food
selections
• Relaxation techniques such as
meditation
• Exercise
• Supportive friendships/relationships
• Spiritual Support
• Laughter
• Professional counseling
• Other
Some Herbs Traditionally Used to
Manage Stress
•
•
•
•
•
Magnolia officinalis
Phellodendron amurense
Withania somnifera (Ashwagandha)
Lagerstroemia speciosa (Banaba)
Rhaponticum carthamoides (Maral) (Effects
of rhaponticum carthamoides versus
glycyrrhiza glabra and punica granatum
extracts on metabolic syndrome signs in
rats)
…and
• L- theanine
•
•
•
•
•
…”a combination of Magnolia bark extract and
Phellodendron bark extract (Relora®) reduces cortisol
exposure and perceived daily stress, while improving a
variety of mood state parameters, including lower
fatigue and higher vigor. These results suggest an
effective natural approach to modulating the
detrimental health effects of chronic stress in
moderately stressed adults.”
•
•
J Int Soc Sports Nutr. 2013 Aug 7;10(1):37. doi: 10.1186/15502783-10-37.
Talbott SM1, Talbott JA, Pugh M.
Magnolia (Magnolia officinalis) and Phellodendron (Phellodendron
amurense) barks are medicinal plants commonly used as
traditional remedies for reducing stress and anxiety. Modern
dietary supplements are intended to induce relaxation and reduce
stress as well as stress-related eating. Previous studies have
shown the combination of Magnolia/Phellodendron (MP) to
reduce both cortisol exposure and the perception of
stress/anxiety, while improving weight loss in subjects with stressrelated eating. Competitive athletes are "stressed" by their
intense exercise regimens in addition to their normal activities of
daily living and thus may benefit from a natural therapy intended
to modulate baseline perceptions of stress and stress hormone
exposure.
METHODS:
We assessed salivary cortisol exposure and psychological mood
state in 56 subjects (35 men and 21 women) screened for
moderate stress and supplemented with a standardized/patented
MP combination (Relora®, Next Pharmaceuticals) or Placebo for 4
weeks.
RESULTS:
After 4 weeks of supplementation, salivary cortisol exposure was
significantly (p<0.05) lower (-18%) in the Relora group compared
to Placebo. Compared to Placebo, the Relora group had
significantly better (p<0.05) mood state parameters, including
lower indices of Overall Stress (-11%), Tension (-13%), Depression
(-20%), Anger (-42%), Fatigue (-31%), and Confusion (-27%), and
higher indices of Global Mood State (+11%) and Vigor (+18%).
Effect of Magnolia officinalis and Phellodendron
Amurense (Relora®) on cortisol and psychological mood
state in moderately stressed subjects.
Salivary Cortisol (ug/ml). Salivary cortisol was
18% lower (p<0.05) in the Relora group
compared to Placebo at Week 4 (0.525+0.190
to 0.642+0.353).
Profile of Mood States (POMS). Numerical
scores for each of the 6 subscales of the POMS
(McNair et al., [9]). The Relora group showed
significantly improved mood state parameters
compared to Placebo at Week 4 (* = p<0,05).
Talbott et al. Journal of the International Society of Sports Nutrition 2013, 10:37 http://www.jissn.com/content/10/1/37
Effect of a proprietary Magnolia and Phellodendron
extract on weight management: a pilot, double-blind,
placebo-controlled clinical trial.
•
N=28 , healthy, overweight (BMI 25 to 34.9), premenopausal
female adults, 20 and 50 years, who typically eat more in response
to stressful situations and scored above the national mean for
women on self-reported anxiety
•
250 mg cap w herbal extracts or placebo cap TID x 6 wks.
•
Measured salivary cortisol levels, weight change, psychological
measures of stress and anxiety.
•
Continued on next slide…..
•
Altern Ther Health Med. 2006 Jan-Feb;12(1):50-4. [PMID:
16454147 ]
Effect of Magnolia officinalis and Phellodendron
Amurense (Relora®) on cortisol and psychological mood
state in moderately stressed subjects.
•
Extracts of M officinalis and P amurense were well tolerated.
•
Results: The treatment group tended to have lower levels of cortisol in the evening;
whereas the control group tended to have higher levels of cortisol in the evening. Bedtime
cortisol levels decreased in the treatment group and increased in the placebo group.
– Placebo group had significant weight gain (P < ,01); Magnolia and Phellodendron group had no significant
weight gain (P < .89).
– Participants in both the treatment and placebo groups had improved scores on a number of psychological
measures during the study. There was a correlation between perceived stress and weight change.
• “The results of this pilot clinical study indicate that obese subjects who eat in
response to stress may benefit from taking a dietary supplement ingredient
containing proprietary extracts of M officinalis and P amurense. The mechanism of
action appears to be through reduction of cortisol levels and possibly perceived
stress, thereby helping participants maintain body weight. The sample size was
small, however, and there was higher attrition in the control group than in the
treatment group.”
Altern Ther Health Med. 2006 Jan-Feb;12(1):50-4. [PMID: 16454147 ]
A standardized Withania somnifera extract (WSE) significantly
reduces stress-related parameters in chronically stressed
humans; a double-blind, randomized, placebo-controlled study
Results:
> Subjects taking lowest dose - significant
reductions on the Hamilton Anxiety Scale
(HAM-A), reduced levels of cortisol and C
reactive protein, drop in pulse rates and BP
compared to placebo.
> Subjects taking lowest dose - significant
increases in DHEA and hemoglobin.
> Response on all measures - dose-dependent
> Compared to control, subjects taking WSE less fatigue, headache and muscle pain,
sleeplessness, forgetfulness, feelings of doom,
and irritability. WSE group - better appetite
and concentration.
> No reports of adverse side effects.
Conclusion:
“Our findings that WSE reduces experiential feelings of
stress and anxiety at all dosage levels tested supports the
traditional claims of WSE's anti-stress adaptogenic effect.”
•
•
•
•
•
•
•
•
Study Design:
Randomized, DBPC. Subjects took WSE or a placebo.
Stress levels measured baseline, 30 & 60d
Subjects:
130 chronically stressed subjects (98 completed)
Dosage:
125 mg QD, 125 mg BID, or 250 mg of WSE BID, or a
placebo x 60 days
Subjects taking the lowest dose saw significant
reductions on the Hamilton Anxiety Scale (HAM-A),
and in their levels of cortisol and Creactive protein as
well as their pulse rates and blood pressure,
compared to placebo.
Subjects taking lowest dose also had significant
increases in DHEA and hemoglobin.
Dose-dependent responses on all these measures.
Subjects taking the withania somnifera experienced
less fatigue, headache and muscle pain,
sleeplessness, forgetfulness, feelings of doom, and
irritability than the control group. In addition, they
had better appetite and concentration.
There were no reports of adverse side effects.
JANA. 2008;11(1):50-56.
Evaluation of a Highly Standardized Withania Somnifera Extract on
Endothelial Dysfunction and Biomarkers of Oxidative Stress in Patients
with Type 2 Diabetes Mellitus: A Randomized, Double Blind, Placebo
Controlled Study.
•
•
•
•
66 subjects on metformin - placebo or 250 mg WSE bid or 500 mg WSE bid X 12 wks
Withania somnifera (Ashwagandha) – used aqueous roots extract highly standardized by
HPLC - not < 10% withanolide glycosides, not > 0.5% of Withaferin-A and not < 32% of
oligosaccharides
Primary efficacy measure - change in endothelial dysfunction, assessed by > 6% change in
reflection index at 12 weeks in all Tx groups
Secondary efficacy parameters -change in oxidative stress markers (malondialdehyde,
nitric oxide and glutathione), serum levels of nitric oxide, hsCRP and lipid profile at 12
weeks in all TX groups. Safety and tolerability also assessed.
• “Conclusion: Withania somnifera showed significant
improvement in endothelial function, reduction in
biomarkers of oxidative stress and systemic inflammation and
can be used as a therapeutic adjunctive in patients with type 2 Diabetes mellitus.”
Int. J. Ayur. Pharma Research. 2014;2(3):22-32
Anti-stress effect of theanine on students during pharmacy practice: positive
correlation among salivary α-amylase activity, trait anxiety and subjective stress
•
•
•
SBPC, n= 20, 5thyr pharmacy students
200 mg Theanine bid after breakfast and lunch, one wk prior to pharmacy practice and 10 days into practice period.
State-trait anxiety inventory test & Salivary α-amylase activity sAA (marker of sympathetic NS activity)
•
RESULTS:
•
•
•
Morning sAA (pre-practice sAA) was higher in placebo than in theanine-group during the pharmacy practice (p=0.032).
Subjective stress was significantly lower in the theanine-group than in the placebo-group (p=0.020).
Students with higher pre-practice sAA showed significantly higher trait anxiety in both groups (p=0.015). Similarly, higher
pre-practice sAA was correlated to shorter sleeping time in both groups (p=0.41×10(-3)).
• CONCLUSION:
• Stressful condition increased the level of sAA that was essentially
affected by individual trait anxiety. The low levels of pre-practice sAA
and subjective stress in the theanine-group suggest that theanine
intake suppressed initial stress response of students assigned for a
long-term commitment of pharmacy practice
Pharmacol Biochem Behav. 2013 Oct;111:128-35. doi: 10.1016/j.pbb.2013.09.004. Epub 2013 Sep 16.[PMID: 24051231]
What are the objectives?
• Help the Body Cope with the
Physiological Effects of Stress
• Support Healthy Cortisol Levels
• Support Relaxation and Restful
Sleep
• Promote Mental Clarity
• Help Alleviate Fatigue
The effects of L-theanine (Suntheanine®) on objective sleep quality in
boys with attention deficit hyperactivity disorder (ADHD): a randomized,
double-blind, placebo-controlled clinical trial.
•
Protocol:
Subjects:
n=98, ages 8-12 years, w ADHD.
Equal distribution of stimulant/non-stimulant treated subjects
in active and placebo groups.
– two chewable tablets bid (at breakfast and after school), with each tablet containing 100
mg of L-theanine (total 400 mg daily Suntheanine®) or identical tasting chewable placebo
for six weeks.
– Eval x five consecutive nights using wrist actigraphy baseline/end.
– Parents completed Pediatric Sleep Questionnaire (PSQ) baseline/end.
•
Results:
– Boys who consumed L-theanine obtained significantly higher sleep percentage and
sleep efficiency scores
– L-theanine at relatively high doses was well tolerated with no significant adverse events.
• This study demonstrates that 400 mg daily of L-theanine is safe
and effective in improving some aspects of sleep quality in boys
diagnosed with ADHD.”
Lyon MR, Kapoor MP, Juneja LR. Altern Med Rev. 2011 Dec;16(4):348-54. [PMID: 22214254]. Full study:
http://www.altmedrev.com/publications/16/4/348.pdf
L-theanine partially counteracts caffeineinduced sleep disturbances in rats.
•
•
•
•
•
•
Jang HS1, Jung JY, Jang IS, Jang KH, Kim SH, Ha JH, Suk K, Lee MG.
Abstract
L-theanine has been reported to inhibit the excitatory effects of caffeine.
The present study examined the effects of L-theanine on caffeine-induced
sleep disturbances in rats. Rats received the following drug pairings: saline
and saline (Control), 7.5 mg/kg caffeine and saline, or 7.5 mg/kg of caffeine
followed by various doses of L-theanine (22.5, 37.5, 75, or 150 mg/kg).
Vigilance states were divided into: wakefulness (W), transition to slow-wave
sleep (tSWS), slow-wave sleep (SWS), and rapid-eye-movement sleep
(REMS). Caffeine significantly increased the duration of W and decreased
the duration of SWS and REMS compared to the Control. Although Ltheanine failed to reverse the caffeine-induced W increase, at 22.5 and 37.5
mg/kg (but not at 75 and 150 mg/kg), it significantly reversed caffeineinduced decreases in SWS. In conclusion, low doses of L-theanine can
partially reverse caffeine-induced reductions in SWS; however, effects of Ltheanine on caffeine-induced insomnia do not appear to increase dosedependently.
Copyright © 2012 Elsevier Inc. All rights reserved.
PMID: 22285321
Pharmacol Biochem Behav. 2012 Apr;101(2):217-21. doi: 10.1016/j.pbb.2012.01.011.
Epub 2012 Jan 21. [PMID: 22285321]
What are the objectives?
• Help the Body Cope with the
Physiological Effects of Stress
• Support Healthy Cortisol Levels
• Support Relaxation and Restful Sleep
• Promote Mental Clarity
• Help Alleviate Fatigue
Effect of standardized aqueous extract of Withania
somnifera on tests of cognitive and psychomotor
performance in healthy human participants.
N=20 healthy males
250 mg two capsules
twice daily WSE or
matching placebo for
a period of 14 days.
RT = reaction time
DSST = digital symbol
substitution test
DVT = digit vigilance test
CST = card sorting test
FTT = finger tapping test
SRT =simple reaction test
CDT =Choice descrimination test
Compared to placebo, statistical difference
between WSE and placebo in RT for CDT, DSST, DVT
Pingali U, Pilli R, Fatima N. Pharmacognosy Res. 2014 Jan;6(1):12-8. doi: 10.4103/0974-8490.122912. PubMed PMID:
24497737; PubMed Central PMCID:PMC3897003. Full study: http://www.phcogres.com/article.asp?issn=09748490;year=2014;volume=6;issue=1;spage=12;epage=18;aulast=Pingali
Randomized placebo-controlled adjunctive study
of an extract of withania somnifera for cognitive
dysfunction in bipolar disorder
• N= 60 euthymic subjects w DSM-IV bipolar disorder
• Placebo or WSE 500 mg/d as a procognitive agent added to
bipolar disorder meds.
• significantly > improvement - mean digit span backward,
neutral mean response time and the mean social
cognition response rating
clinicaltrials.gov (identifier: NCT00761761).
Chengappa KN, Bowie CR, Schlicht PJ, Fleet D, Brar JS, Jindal R. J Clin Psychiatry. 2013 Nov;74(11):1076-83. doi:
10.4088/JCP.13m08413. PubMed PMID: 24330893. Full study:
http://www.psychiatrist.com/jcp/article/Pages/2013/v74n11/v74n1107.aspx
What are the objectives?
• Help the Body Cope with the
Physiological Effects of Stress
• Support Healthy Cortisol Levels
• Support Relaxation and Restful Sleep
• Promote Mental Clarity
• Help Alleviate Fatigue
Adaptogens: tonic herbs for fatigue
and stress.
•
Panossian A. Alt Comp Ther 2003;Dec:327-31.
http://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=1&ved=0
CCEQFjAA&url=http%3A%2F%2Fwww.researchgate.net%2Fprofile%2FAlexande
r_Panossian2%2Fpublication%2F244889830_Adaptogens_Tonic_Herbs_for_Fati
gue_and_Stress%2Flinks%2F0c960521c4f911f827000000.pdf&ei=EOjwVODyO4
79oQT02YDoCg&usg=AFQjCNGmbpu4VMkvMZsuhfBFGss_YwbQSQ&bvm=bv.8
7269000,d.cGU
Great full article that covers many aspects of adaptogens in
general and includes SWE, magnolia, phelledron, and
Rhaponticum carthamoides (maral)
---Improved Quality of Life
Effects of Magnolia officinalis and Phellodendron
amurense (Relora) on Cortisol and Psychological
Mood State in Moderately Stressed Subjects
• Double-blind, placebo-controlled
Subjects: 35 men and 21 women screened for
moderate stress
Age range: 19-59 with an average age of 28
Duration: 4 weeks
Relora Group: 500mg/day
No adverse effects reported
Fatigue decreased
over 30%
J Int Soc Sports Nutr. 2013 Aug 7;10(1):37. doi: 10.1186/1550-2783-10-37.
We have examined studies demonstrating ingredients that
meet stress management objectives. Medical conditions
were mentioned. Now we will discuss a dietary supplement.
•It is important to remember that dietary
supplements CANNOT mitigate diseases or
replace drugs.
•However, XYMOGEN products CAN give your
patients their best chance to stay healthier
longer*
* These statements have not been evaluated by the US Food and Drug Administration. These products are
not intended to diagnose, treat, cure , or prevent any disease.
Introducing
CortiSolv™
Natural Stress Buster*
*These statements have not been evaluated by the Food and Drug Administration. This product is not
intended to diagnose, treat, cure, or prevent any disease.
Five stress-busting ingredients*
Cortisolv™ Supplement Facts Serving Size: 1 Capsule
Amount Per Serving
Relora†® (a proprietary blend of a
250 mg
patented†† extract from
Magnolia officinalis bark and a
proprietary extract from
Phellodendron amurense bark)
Sensoril® Ashwagandha
(Withania somnifera) Root and
Leaf Extract (10% withanolides)
%Daily Value
**
150 mg
Suntheanine® L-Theanine
100 mg
Banaba Leaf Extract
50 mg
(Lagerstroemia speciosa)(1%
corosolic acid)
Maral Extract (Rhaponticum
50 mg
carthamoides)(root)
** Daily Value not established
Other Ingredients: HPMC (capsule), L-leucine, ascorbyl palmitate, medium-chain
triglyceride oil, silica, and microcrystalline cellulose.
**
**
**
**
Relora®
• All-natural, Non-irradiated, Non-ETO*
treated, Non-GMO, vegetarian
• Proprietary blend of patented extract
Magnolia officinalis bark and
Phellodendron amurense bark
• Well-studied by third parties
* ethylene oxide
A Brief Summary of Relora Clinical Trials
Reference
Type of Study
# Participants
Dosage
Outcome
Kalman DS,
Feldman S,
Feldman R, et al.
Nut J. 2008;7:11
Randomized, parallel,
placebo controlled
study
26 healthy, overweight
(BMI 25 – 34.9),
premenopausal
females
250mg 3 times daily
for 6 wks
In comparison to placebo,
significantly reduced
temporary, transitory
anxiety as measured by
Spielberger STATE anxiety
questionnaire *
Garrison R,
Chambliss WG.
Altern Ther
Health Med.
2006;12(1):50-4.
Randomized, doubleblind, placebocontrolled pilot clinical
study
26 healthy,
overweight,
premenopausal
female adults, 20-50
yrs of age
250mg 3 times daily
for 6 weeks
Weight gain less in those
taking Relora than in
placebo due to lowered
cortisol levels *
*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure,
or prevent any disease.
A Brief Summary of Relora Clinical Trials (Cont’d)
Reference
Type of Study
# Participants
Dosage
Outcome
LaValle J. Unpublished
Data
Open label, single
center, pilot
clinical trial
12 subjects with
mild to moderate
stress (27 – 52
yrs)
250mg 3 times
daily for 14 days
Salivary cortisol and DHEA
levels were checked; marked
reduction in morning cortisol
occurred and an
improvement in DHEA levels
*
Talbot SM. Unpublished
Data
Randomized
placebocontrolled,
double- blind
clinical trial
56 subjects (35
men, 21 women)
250mg 2 times
a day for 4
weeks
Improvement in salivary
cortisol levels, mood, and
other indices of overall
health*
*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or
prevent any disease.
Sensoril®
• Optimized ashwagandha (Withania
somnifera) root and leaf extract
• Proprietary/patented extraction process
produces very high, powerful levels of
stress-fighting, cognition-enhancing
ashwagandha bioactive constituents.*
• Standardized to a minimum of 10%
glycowithanolides.
• Subject of five RDBC human clinical trials
• excellent safety record*
*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat,
cure, or prevent any disease.
Sensoril® Mechanism of Action:
• Active constituents, glycowithanolides, a
type of steroidal lactone imitate certain
corticosteroids which shut off the stress
response, protecting the body against
the harmful effects of prolonged stress
or overreaction to stressors.*
– As a result of their mimicking action,
glycowithanolides decrease serum
cortisol*
*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose,
treat, cure, or prevent any disease.
Suntheanine®
• Pure form of L-theanine produced via a
patented fermentation process
• 100% pure L-isomer-theanine
• Shown to be safe based on numerous
favorable toxicology and efficacy studies*
• Does not cause drowsiness*
• GRAS Affirmation (Generally Recognized as
Safe) of Suntheanine received confirmation
from the US FDA in 2007 (GRN 000209).
*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure,
or prevent any disease.
Banaba (Lagerstroemia speciosa)
• Leaf extract
• Long history of use in folk medicine, particularly
in SE Asia as a glucose modulator*
• Animal & human research on banaba leaf and
its actives, including corosolic acid, suggest
multiple mechanisms that influence glucose and
lipid metabolism.*[1,2]
• Standardized to 1% corosilic acid
– corosolic acid inhibits the enzyme that
facilitates the conversion of cortisone to
cortisol.*[3]
1.) Evid Based Complement Alternat Med. 2012;2012:871495. [PMID: 23082086]
2.) Biol Pharm Bull. 2004 Jul;27(7):1103-05. [PMID: 15256748 ]
3.) Bioorg Med Chem. 2010 Feb 15;18(4):1507-15. [PMID: 20100662]
*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat,
cure, or prevent any disease.
Maral Extract
Rhaponticum cathamoides
• Root
• Widely used in traditional Siberian medicine, mainly
to treat overstrain and common weakness resulting
from illness. It has also been used historically as a
stimulant.
• Main bioactive constituents -ecdysteroids, flavonoids,
and phenolic acids.[1]
• “adaptogenic herbal remedy.”*[1]
• Preliminary animal research suggests –
– lowers corticosterone levels
– positively influences glucose and fat
metabolism.*[2]
1.) Phytochemistry. 2009 May;70(7):842-55. [PMID: 19457517]
2.) BMC Complement Altern Med. 2014 Jan 29; 14:33. [PMID: 24444255]
General Information - CortiSolv
• DIRECTIONS: Take one capsule twice daily, or
as directed by your healthcare practitioner.
• Consult your healthcare practitioner prior to
use. Individuals taking medication should
discuss potential interactions with their
healthcare practitioner. Do not use if tamper
seal is damaged.
• STORAGE: Keep tightly closed in a cool, dry
place out of reach of children.
• DOES NOT CONTAIN: Wheat, gluten, yeast, soy,
dairy products, fish, shellfish, peanuts, tree
nuts, ingredients derived from genetically
modified organisms (GMOs), artificial colors,
artificial sweeteners, or artificial preservatives.
High Cortisol:
• Adrenal Stress Test: Treatment Recommendations
• : 1 scoop before bed, or when cortisol peaks to
calm the effects of RelaxMax: symptoms
• Sedalin: 1-2 before bed
• Cortisolv before bed to oppose action of cortisol.
This botanical is very useful for those that feel
“tired but wired,” a since of anxiety, of insomnia.
Ashwaganda can help to give people more energy
without increasing anxiety, it can also help to turn
off racing thoughts to improve sleep.
• Melatonin can be used to oppose high cortisol and
protect the brain from free radicals while sleeping.
Controlled release melatonin releases first to put
you to sleep, but again 4 hours later, so you stay
asleep.
Stress and Melatonin
•
•
•
•
•
•
•
•
Biomed Khim. 2015 May;61(3):394-399. doi: 10.18097/PBMC20156103394.
[Effect of melatonin on antioxidant enzyme activities in blood erythrocytes of rats during acute
emotional stress].
[Article in Russian]
Pertsov SS1, Kalinichenko LS1, Koplik EV1, Nagler LG2, Alinkina ES2, Kozachenko AI2.
Author information
Abstract
in English, Russian
The effect of the epiphyseal hormone melatonin on the activity of antioxidant
enzymes, glutathione peroxidase (GPx), glutathione reductase (GR), and Cu/Zn-superoxide dismutase
(Cu/Zn-SOD) was studied in peripheral blood erythrocytes of behaviorally passive and active Wistar
rats. Acute emotional stress was modeled by immobilization of animals for1 h with simultaneous
electrocutaneous stimulation. Basal activity of antioxidantglutathione enzymes in erythrocytes of
behaviorally passive rats was higher than that in active animals. Administration of melatonin (2 mg/kg,
intraperitoneally) was accompanied by a decrease in the activity of GPx and GR in erythrocytes from
non-stressed passive animals. After experimental stress, passive rats demonstrated a significant
increase in the activity of Cu/Zn-SOD and GPx in peripheral blood erythrocytes. The absence of stressinduced changes in functional activity of antioxidant defense enzymes in the blood of behaviorally
active animals suggests a relatively constant oxidative status of tissues in these animals
under stress conditions. Melatonin administration had little effect on stress-induced changes in
functional activity of the erythrocyte antioxidant system in passive rats. Active specimens pretreated
with melatonin before stressexposure were characterized by activation of study antioxidant enzymes.
Quantitative parameters of the erythrocyte antioxidant defense enzymes did not differ in behaviorally
active and passive rats subjected to experimental stress after melatonin injection. Thus, exogenous
melatonin abolishes differences in the activity of study antioxidant enzymes in erythrocytes of animals
with different behavioral parameters under basal conditions and after experimental stress. In passive
rats melatonin mainly reduced the initial tension of oxidative processes. By contrast, administration of
this hormone to active specimens is followed by an increase in functional activity of the antioxidant
enzyme system under conditions of acute stress.
Melatonin as gut treatment?
J Physiol Pharmacol. 2008 Aug;59 Suppl 2:33-51.
Thirty four years since the discovery of gastrointestinal melatonin.
Bubenik GA.
Department of Integrative Biology, University of Guelph, Guelph, Ontario, Canada. [email protected]
After the discovery of melatonin in the pineal gland by Lerner and co-workers in 1958, melatonin was also
detected in the retina and the human appendix. Later, melatonin was confirmed immunohistologically in
all segments of the gastrointestinal tract (GIT), in the guts of bovine embryos and in the GIT of low
vertebrates. Melatonin was also confirmed in the pancreas and the hepatobiliary system. Melatonin is
produced in the enteroendocrine cells of the GIT mucosa. The concentrations of melatonin in the GIT
are 10-100x higher than in the plasma and the total amount of melatonin in the GIT is around 400x
higher than the amount of melatonin in the pineal gland. Similar to pineal melatonin, GIT melatonin is a
multifunctional compound which exhibits some general as well as some specific effects, depending on
the organ and the location of GIT tissue. In the GIT, melatonin exhibits endocrine, paracrine, autocrine
and luminal actions. Generally, the episodic secretion of melatonin from the GIT is related to the intake
and digestion of food and to the prevention of tissue damage caused by hydrochloric acid and digestive
enzymes. Some actions, such as the scavenging of hydroxyl free radicals, immunoenhancement and
antioxidant effects are of general nature, whereas others, such as an increase of mucosal blood flow, the
reduction of peristalsis and the regulation of fecal water content, are specific to the tubular GIT.
Generally, melatonin actions oppose those of serotonin. Laboratory and clinical studies indicate that the
utilization of melatonin can prevent or treat pathological conditions such as esophageal and gastric
ulcers, pancreatitis, colitis, irritable bowel disease, and colon cancer.
Low Cortisol:
•
•
•
•
•
AdrenaMax or Tyrosine: 1-2, in the am and afternoon as
needed to provide the amino acid tyrosine to increase
production of cortisol.
Licorice will potentiate cortisol and other ginsengs will improve
adrenal function. These herbs are known to be adaptocrines
which means improving adrenal function when high or low.
Will improve energy and mood, as well as immune function.
CortiCare: 1-2, one to two times a day to rebuild adrenal
health. This provides critical nutrients such as B5, B6 and
Vitamin C to build adrenal function so they begin to make their
own cortisol. These nutrients repair the ware and tear of stress
on adrenal function.
AppeCurb: Amino acid precursors for epinephrine and
norepinephrine tyrosine and phenylalanine. Both of which
improve energy, focus and concentration. This will improve
concentration, and also increase other neurotransmitters
which help with a sense of well-being.
AdrenaEssence-glandular (ProAdrenal)
High DHEA:
• TREAT THE STRESS
• I5-to balance hormones and lower
overproduction of DHEA. High DHEA could be
associated with conditions such as polycyctic
ovarian syndrome. Some people may have
difficulty converting DHEA to testosterone.
Optimal Cleanse helps to aid this conversion.
• RelaxMax-1 scoop once a day to two times a
day to offset irritability from high androgens
and to augment progesteronic activity through
inositol helping ovarin function and GABA
acting synergistically with progesterone in the
body.
Low DHEA
• DHEA: 5-20mg for a female, 25-75mg for
a male. Low DHEA may contribute to
fatigue and hormonal imbalances.
Increasing levels improves energy,
mood, and fertility.
• DHEA helps to maintain strength and
stamina and supports testosterone
production.
High sIgA
• Identify and treat possible infection—
Berbermycin, Candicidal can be used to
treat the infection present. A typical
dose of 1-3, 1-3x a day can be deployed
based on severity. These are
combinations of botanicals designed to
decrease bacterial, yeast or parasitic
overgrowth.
• Immunoglobulins (IgG CWP)
Low sIgA
sIgA makes up 85% of our immune function. It lines our gut and is our
first line of defense from the outside world. It plays a role in immune
tolerance and inflammation.
Immunoglobulins
Treat The Stress
I5
ProbioMax
GI Protect
GlutAloeMine
Pancreatic Enzyme
GastrAcid
GastAcid
Sacchromycin DF
Vitamin A
Vitamin A
Adrenals And Stress
• Adrenals help to manage stress
• Stress can damage adrenals (its
bidirectional)
• As adrenal function is built we become
more resistant to stress
• Treating the adrenals gives us a way to
treat stress when we can’t treat the
“cause”
When To Order Adrenal Stress Testing
•
•
•
•
•
•
•
Fatigue
Hypoglycemic Symptoms
Menopausal
Brain fog
Worse under stress
Insomnia
Any one who we want to be optimized
in the face of stress
Adrenal Treatments
• Tired But Wired: CortiSolv, RelaxMax
• Tired and Wired ++ : CortiSolv,
RelaxMax, CortiCare
• Tired And Tired: Adrenal Manager and
CortiCare
• Tired and Sick: Adrenal Essence
(Cordyceps), CortiSolv
• Tired and Depressed: AdrenaMax
(Tyrosine)
Stress
• Stress has direct effects right down to the
tissue
• Stress changes enzyme activity
• Stress makes a cancer more aggressive, and
more likely to pass the blood brain barrier
• Stress plays a roll in auto-immune
conditions
• Stress, like temperature, cooks our
environment to determine our biochemical
function