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Sanjay Kapur, MD
BiographyDr. Sanjay Kapur is the CEO at AYUMETRIX, a Research and
Diagnostic Organization that offers specialized high complexityfunctional laboratory consulting services for platform technology firmsand diagnostic companies. He is an internationally known andrecognized anti-aging expert, with dozens of peer-reviewedpublications and abstracts, as well as numerous invited presentations.He is a highly-sought speaker on health and wellness at internationalmedical conferences. Dr. Kapur’s strong desire and passion toeducate physicians all around the world motivated him to found theSociety for Regenerative, Aesthetics and Anti-Aging Society of India.He also serves on Editorial and Scientific Boards of several scientificjournals and international anti-aging societies.
Stress and Cardiovascular Disease:Is Cortisol the Key?
Dr. Sanjay KapurFounder President & CEO
If you say “NO” then Sit Down
• You are NOT a smoker• Your BMI ≤ 25 Kg/m2
• You exercise at least 30 min/ day for 5 days a week• You eat at least 5 servings of fresh fruits and
vegetables every day• You don’t consume alcohol or only once or twice
every week ( not more than one drink each time)• You have no stress
Cardiovascular Disease
950,000 Americans die of CVD each year
1 Death every 34 seconds
>150,000 who die of CVD are <65 years of age
Diabetes Mellitus
23.6 Million Americans have diabetes
Prevalence has increased by 61% since 1990
Diagnosed: 17.9 million
Undiagnosed: 5.7 million
What Happened? Where Did We Go Wrong?
Changes in our lifestyle
Changes in Eating Patterns
Is It Sugar Consumption?
Changes in Physical Activity
Increased Lifestyle Stress (Loss of Normal Rhythms
Adrenal Hormones
Medulla
Zona Glomerulosa
Zona Reticularis
Zona Fasciculata
Adrenal Cortex
Aldosterone
Cortisol and Cortisone
Pregnenolone, Progesterone, estrogens, testosterone, DHEA, androstenedione
Epinephrine (adrenalin) and norepinephrine(noradrenalin)
Capsule
Cortisol
The principle stress hormone
Increases heart rate
Increases blood pressure
Dilates airways, increases respiratory rate
Increases blood sugar
Releases fatty acids into the blood
Suppresses immune function
Breaks down muscle
Positive Effects of Increased Cortisol
A quick burst of energy for survival reasons
Heightened memory functions
A burst of increased immunity
Lower sensitivity to pain
Helps maintain homeostasis in the body
Negative Effects of Increased Cortisol
Impaired cognitive performance
Suppressed thyroid function
Blood sugar imbalance like hyperglycemia
Decreased bone density
Decrease in muscle tissue
Lowered immunity and inflammatory response
Increased abdominal fat
The stress-response is supposed to be short-lived
Biphasic Response to Stress
Effects of Chronically High Cortisol
Cushing’s Syndrome (Hypercortisolism)
Weight gain, abdominal obesity, rounded face
Weakened bones and muscle
Easily bruised skin, other skin problems
High blood pressure
Chronic Stress Response- Pregnenolone Steal
X
X
X
XX
XXX X
Chronic Stress Response- Pregnenolone Steal
Salivary Testing of Cortisol
Obesity: What happens in the adipocyte?
Android (Apple) vs. Gynoid (Pear) Obesity
Jean Vague (1947)
ATribute
to a Pioneer:
Vague J. Presse Med 1947;30:339–340.
The Metabolic Syndrome: Integration of Multiple CV Risk Factors
Body SizeBMI
Central Adiposity
Insulin Resistance
Glucose Metabolism
Uric AcidMetabolism Dyslipidemia Hemodynamic Hypercoag
Uric AcidUrinary uric acid clearance
PP-glucoseIFGIGTT2DM
TGPP lipemiaHDL-CPHLASmall, denseLDL
SNS ActivityNa retentionHypertension
CRPPAI-1Fibrinogen
Coronary Heart Disease
Neuroendocrine stress axes are activated in Metabolic Syndrome.
The case control study provides the first evidence that chronic stressMay be a cause of Metabolic Syndrome.
Waist-to-hip ratio in men positively correlated with cortisol response to waking.
Negative correlation of waking response and HDL.
Positive correlation with LDL.
CS induces not only LV hypertrophy and diastolic dysfunction but alsoSubclinical LV systolic dysfunction, which reverses upon normalization ofCorticosteroid excess
…revealed that endothelial dysfunction in CS patients is related to hypercortisolemia and is reversible after treatment, suggesting the possible role of cortisol excess in development of endothelial dysfunction,thereby possibly leading to increased cardiovascular complications
Strong association between Cushing’s syndrome, characterized by a Cluster of systemic complications and increased cardiovascular risk.
The biological link is cortisol overproduction.
Hypercortisolism
Vascular damage
Hypertension Left ventricular remodellingdysfunction
Prothrombotic state Central obesity and Metabolic alterations
Increased cardiovascular risk
Mechanisms of increased cardiovascular risk mediated by hypercortisolism
Laboratory Hormone Assessment
Lab assessment of adrenal hormones-Cortisol and DHEA
Measure Androgen levels- Testosterone
Test for changes in sex hormones-Estrogens and Progesterone
Test for Insulin Resistance and glucose dysregulation
HOW TO TEST CORTISOL LEVELS?
Salivary cortisol seem to be a good screening tool based on itsnon-invasive nature, remarkable reproducibility anddiagnostic performance.
HOW TO BRING CORTISOL LEVELS BACK TO NORMAL?
The Science of MEDITATION
Reversal of atherosclerosis Reduction of myocardial ischemia Reduced health insurance claims for CVD Reduced mortality
Encouraging Exercise
Recommend atleast 150 minutes per week of moderate aerobic or 90 minutes vigorous aerobic activity to improve glycemic control, weight management and reduce CVD risk.
Advise patients to start slowly and gradually build intensity.
Discuss benefits with patients (social, psychological, physical).
Monitor patient’s progress.
Source: ADA
Encouraging Exercise
Source: ADA
Diet Emphasize good quality proteins. Combine unrefined carbohydrates (whole grains)
with good quality protein and oils (nuts and seeds) Use cold pressed oils - olive, walnut, filbert, flax Especially avoid hydrogenated fats and caffeine Emphasize vegetables (alkaline foods) Allow unrefined salt to be added
ad. lib. according to taste
Encouraging Healthy Eating
Eat by 10 AM and again before noon Eat regular meals – chew food well Avoid
Hydrogenated fats Caffeine containing foods and beverages Chocolate White carbohydrates (white sugar, white flour) Junk foods Allergenic or sensitive foods
Digestive aids will be needed by most until recovery is more complete.
Encouraging Healthy Eating
Nutrients that Support Adrenal Function
Vitamin C B Vitamins Calcium and magnesium Zinc, selenium, copper Sodium Manganese
Adrenal glandular
Theanine
Digestive aids will be needed by most until recovery is more complete
Dietary Supplements for Adrenal Fatigue
Vitamin C 2,000 - 5,000 mg/day 1:2 ratio of bio-flavinoids to C
Vitamin E with mixed tocopherols 800 IU/day
Panthothenic acid (B5) 1500 mg daily
Calcium (malate/citrate) 800 mg
Magnesium (glycinate/citrate) 400 mg
Organic trace minerals - calming effect
Adaptogens
Ashwagandha Root Powder 3-6 grams daily Note: some products are more concentrated
Siberian Ginseng 2-8 Grams per day dried root 2-4 ml daily of fluid extract (1:1dilution)
Licorice Root Powder Standardize extract 2 to 3 grams per day (200-300 mg glycyrrhiza)
Maca Root 5-10 g bid dried root powder
Rhodiola 250 mg 1-3 times a day
Holy Basil 400-800 mg bid (standardized. to 1% ursolic acid)
Cortisol has connection with heart disease but it may be possible to
prevent or reverse the adverse effects
Adaptogens
Ashwagandha
Siberian Ginseng
Licorice
Maca
Rhodiola
Holy Basil
•Cordyceps
•BacopaUsed to control high or fluctuating cortisollevels without dropping normal or low levels
Adaptogens
Ashwagandha (Withania somnifera)
Cardiotropic Cardioprotective Anticoagulant properties Anabolic activity Immunomodulator
(Dhuley JN. J Ethnopharmacol 2000 Apr;70(1):57-63
Ashwagandha
Ashwagandha root powder (0.7 and 1.4 g/kg body weight/day) for 30 days produced the following results: Significant decrease in lipid peroxidation
A significant increase in superoxide dismutase
A significant increase in catalase.
Free radical scavenging activity
(Panda S. Kar A. Indian Journal of Physiology & Pharmacology. 41(4):424-6, 1997 Oct.)
Ashwagandha is used in Ayurvedic medicine as a powder, decoction, medicated wine, mixed with clarified butter, combined with honey or sugar syrup or as a medicated oil. The most common form is as an alcoholic extract or capsules, of the powdered root.
Dosage is as follows: Powder:3-6 grams daily or up to 5 to 10 grams as an occasional
tonicDecoction:16 to 31 grams added to heated cow’s milkAlcoholic Extract:2 Tblsp., 2-4 times daily.Mixed with ghee or honey:1 tsp. 2 times dailyNarayana Taila Oil:Internally, 3-10 drops; or freely applied externally to painful, arthritic joints. Contraindications and Toxicity:
Large doses of ashwagandha may possess abortifacient properties so that it should not be taken drink pregnancy unless under the direction of an experienced health professional. It is also contraindicated in conjunction with sedatives or anxioletics (a substance that reduces anxiety) or if one is suffering from stomach ulcers. Traditionally, like other tonics such as ginseng, ashwagandha should not be taken when there are signs of inflammation or advanced arterial congestion. For this reason is may be best to precede or accompany taking it with a general detoxifying herb or formula such as Yogaraj guggul.
Ashwagandha is relatively safe when taken in the prescribed range of dosage. [18] Large doses, however, have been shown to cause gastrointestinal upset, diarrhea and vomiting. Finally, because ashwagandha has been found to potentiate the effects of barbituates, it is generally recommended that it be not taken under such conditions.
Adaptogens
Ginseng Is adaptogenic for stress reducing cortisol when it is too high and
increasing it when too low.
Anti-fatigue, anti-stress, immuno-enhancing effect, CNS activity, and anti-depressive effects.
Siberian ginseng (Eleutherococcus senticosus) < American ginseng (Panax quinquefolium) < Korean ginseng (Panax ginseng) in stimulating effect
Use Korean ginseng for males
Adaptogens
Siberian Ginseng
Typical dose of dried root is 2-8 grams daily For Chronic Fatigue, 2-4 grams tid
Typical dose of the fluid extract is 2-4 ml (1:1 dilution)
Interactions with anti-diabetic meds, cardiac glycosides, stimulants
Caution with hypertension Patients with hypertension should not consume ginseng
Adaptogens
Licorice (Glycyrrhiza glabra) Adrenocorticoid-like activity
Specific for hypoadrenia
Reduces workload of adrenals
Anti-inflammatory, antitussive, antiviral, antiulcer, & estrogen balancing properties
Do not exceed 1/4 lb/day or 1 gram glycyrrhisin (10 grams licorice root) to avoid increase in BP Contraindicated in cases of hypertension
Licorice
Elevates cortisol by blocking conversion of cortisol into cortisone by inhibiting 11beta-hydroxysteroid dehydrogenase(11beta-HSD).
In high doses (3.5 gm/day), it lowers testosterone in women (useful in PCOS, hirsutism)
Adaptogens
Licorice (Glycyrrhiza glabra)
This product is not recommended if you are pregnant. Licorice may increase blood pressure and cause water retention, though some people are more sensitive to this effect than others. Long-term (more than two to three weeks) intake of products containing more than 1 gram of glycyrrhizin (the amount in approximately 10 grams of root, which is far in excess of the daily dosage recommended by this product) is the usual amount required to cause these types of effects. According to the German Commission E monograph, Licorice supplements are contraindicated in people with liver and kidney disorders.
Adaptogens
Maca (Lepidium peruvianum) Enhance fertility in humans and animals.
Anti-stress activity
Eliminates variations in homeostasis produced by stress
Reduces or abolishes stress-induced ulcers
Reduces elevated corticosterone levels
Reduces elevated glucose
Dose: 5-10 g bid dried root powder 2 tsp. of root powder are about 5.5 g
Adaptogens
Rhodiola (Rhodiola rosea)
Helps maintain cAMP levels in myocardium
Increased resistance to a variety of chemical, biological and physical stressors
CNS activities– affects levels of serotonin, dopamine, catecholamine, and opioid peptides
Prevents depletion of adrenal catecholamines induced by acute stress
Adaptogens
Holy Basil (Ocimum sanctum)
Increases recovery from stress (plasma cortisol levels) Immunomodulatory activity Improves gastric mucosal strength Helps normalize blood sugar Increases physical endurance May improve lipid levels Dopaminergic activity Modulates adrenal corticosterone levels (in animals)
Adaptogens
Holy Basil (Ocimum sanctum)
Antioxidant benefits Protects tissue from radiation-induced free radical damage Protects pancreatic beta cells Empirical evidence suggests anti-depressant activity Anti-ulcer activity in animal trials May protect against stress-induced immune alterations.
Adaptogens
Bacopa (Bacopa monnieri)
Beneficial effects on anxiety, as well as mental fatigue
CNS effects believed to be GABAergic system mediated
May affect norepinephrine and serotonin levels
300 mg/day of bacopa extract decreased urinary corticoids and improved cognition, with maximal effect after 12 weeks
Adaptogens Summary
Ashwagandha Root Powder 3-6 grams daily Note: some products are more concentrated
Siberian Ginseng 2-8 Grams per day dried root 2-4 ml daily of fluid extract (1:1dilution)
Licorice Root Powder Standardize extract 2 to 3 grams per day (200-300 mg glycyrrhiza)
Maca Root 5-10 g bid dried root powder
Rhodiola 250 mg 1-3 times a day
Holy Basil 400-800 mg bid (standardized. to 1% ursolic acid)
DHEA
May help to protect from overproduction of cortisol and enhance the immune system
Male dosage 25-50 mgs/day divided into 2-4 doses Female dosage 5-10 mgs/day divided into 2 doses Signs of excess DHEA supplementation:
Females – acne & facial hair usually the first signs of excess, agitation, weight gain
Males – increased aggressiveness, hostility, mood swings, irritability
Adrenal Dysfunction Patterns
Chronic stress elevates cortisol Can be all day, just at night, or during certain times of the day
depending on individual and their stressful circumstances
Adrenals pump out cortisol and other hormones, especially testosterone and DHEA
Testosterone and DHEA levels rise along with cortisol, melatonin decreases
Adrenal Dysfunction Patterns
Adrenals become low on reserves and cannot produce hormones Cortisol levels below normal parts or all the day Cortisol most commonly falls to below normal during the day, AM
cortisol often last to fall Testosterone and DHEA fall along with cortisol
Which hormones drop first varies with individuals Testosterone sometimes goes back up (Compensatory mechanism for energy)
Adrenal Protocols
Assess adrenal function Salivary testing
4 pt cortisol best, 2 pt acceptable, morning only gives limited information High morning cortisol doesn’t indicate reserve capacity of adrenals If morning cortisol low, most likely adrenal fatigue
Questionnaire in “Adrenal Fatigue” by Jim Wilson Energy/Intake 3 day diary
Rate energy level from 1 to 10 at least q 2 hrs Mark times any food, liquid, or nicotine consumed Watch for low energy with stimulant intake
Adrenal Protocols
For any stage of high or low cortisol Adrenals are being stressed and will eventually fatigue Balance stress Exercise Diet improvements Exercise! Determine thyroid function status Exercise!!
Adrenal Protocols
If cortisol is high throughout the day: “Tired but wired”
Water
Weight in pounds ∕ 2 in ounces
Unrefined salt: ½ teaspoonful bid
Adaptogens
PS at 4 pm and 2 hrs before bedtime
Additional Insomnia agents prn
Theanine 100-200mg 2-4 times a day
Magnesium
Adrenal vitamin support: Super Adrenal Stress Form. 1-5 tablets daily
Cortisol elevated AM and at night but low throughout day On way to fatigued adrenal “Wired, then tired, then restless” Water
Weight in pounds ∕ 2 in ounces Unrefined salt: ½ teaspoonful bid Adaptogens PS at 9 pm
Additional Insomnia agents prn Theanine 100-200mg 1 hr before bedtime and in evening prn Magnesium Adrenal vitamin support: Super Adrenal Stress Form. 3-5 tablets daily Adrenal Rebuilder 5-6 tablets daily Replace DHEA and testosterone if low Check Progesterone levels – converting to cortisol?
If cortisol is slightly high or high normal in am but low the rest of the day “Wired then tired” On verge of adrenal fatigue Water
Weight in pounds ∕ 2 in ounces
Unrefined salt: ½ teaspoonful bid Insomnia agents if sleep a problem Adrenal vitamin support: Super Adrenal Stress Form. 4-5 tablets daily Adrenal Rebuilder 6-8 tablets daily Replace DHEA and testosterone if low Check Progesterone levels – converting to cortisol?
Protocols, Cont’d
Cortisol is low all day Water
Weight in pounds ∕ 2 in ounces
Unrefined salt: ½ teaspoonful bid Insomnia agents if sleep a problem Adrenal vitamin support: Super Adrenal Stress Form. 4-5 tablets daily Adrenal Rebuilder 6-8 tablets daily Replace DHEA and testosterone if low Check Progesterone levels – converting to cortisol? Hydrocortisone therapy – taper off as you support Adrenals