Friday, August 8, 2014

What You Need to Know about Stress, Hormones & Weight Management

There’s a famous quote that strikes me as particularly appropriate for a conversation about stress. It’s widely attributed to the Dalai Lama as his reaction to what surprises him most about humanity:
“Man. Because he sacrifices his health in order to make money. Then he sacrifices money to recuperate his health. And then he is so anxious about the future that he does not enjoy the present; the result being that he does not live in the present or the future; he lives as if he is never going to die, and then dies having never really lived.”

Whether he actually said this, I find the point being made to be poignant – especially when we think about the rapidly increasing obesity rates in today’s world.


Today’s Biggest Health Problem?

Most medical experts cite obesity as our most urgent health problem. More than 65% of Americans are overweight to obese, and the numbers are still on the rise. This is in spite of the fact that we have spent billions of dollars on clinical research aimed at solving problems like diabetes, heart disease, high blood pressure, cancer, sleep apnea, and many others – all of which are associated with obesity.

Obesity increases free fatty acids, which leads to dyslipidemia, hypertension, and insulin resistance. This condition, collectively called metabolic syndrome, can progress to type 2 diabetes and/or cardiovascular disease. Obesity also causes mechanical stress to the body, resulting in sleep apnea, osteoarthritis, low back pain, and shortness of breath. Finally, all the hormones in the body become imbalanced as a result of excessive weight, and that can lead to multiple disruptions in hormone-dependent physiological processes, which in themselves contribute to further weight gain.

In the following paragraphs, I would like to focus my discussion on the hormone imbalances caused by obesity, and describe and discuss the hormones that have been implicated in weight gain and obesity, and the physiological reasons why fat accumulation affects hormone levels. At the same time, it is important to discuss the contribution of stress to obesity as cortisol (stress hormone) levels rise, promoting appetite dysregulation, increased blood glucose, and increased visceral fat storage.

The Bad News is Getting Worse

In 1970, 45% of Americans were obese. If you think that sounds bad, read on.

Current projections are that 74% of Americans will be in this category by the year 2020. What happened? Where did we go wrong? Is it that our lifestyles have changed so drastically? Are we eating differently? Is it the sugar consumption and/ or processed foods? Are we not as physically active as we used to be before? Are there any changes in our work habits that we need to look at carefully? Do we have increased lifestyle stress? The answer probably lies in a combination of all these factors, as people pay less and less attention to how their habits and lifestyles contribute to their health.

What can be done to rein in the escalation? How can we lose weight? Weight loss should be very simple according to the rule of calories consumed and calories burned; if we burned more calories than consumed, we should be able to lose weight very easily. Weight loss may not be too difficult for a motivated person who is willing to change their eating and exercise habits and reach a goal, but long-term weight management may be a challenge.


How Stress Impacts Weight Management

For proper weight management, it is extremely important to understand the role of the Hypothalamic-Pituitary-Adrenal (HPA) axis. Any type of stress can lead to HPA dysfunction and related disorders like Cushing’s syndrome, chronic stress, panic disorders, hypothyroidism, adrenal insufficiency, chronic fatigue syndrome, fibromyalgia, etc. Dysregulation of the HPA axis is a leading cause of metabolic problems that can contribute to body fat accumulation. Let us now look at the biochemical processes that are set in motion when the HPA axis is disordered and the end result is increased fat deposition.

The goal of the stress response, a key function of the HPA axis, is to maintain effective blood supply to brain, heart, and skeletal muscle, and to increase production of energy by stimulating gluconeogenesis (endogenous glucose synthesis) and ATP production, needed for the short term response to any chemical or mechanical stress to the body. The main components of the stress response system are the HPA axis and the sympathetic nervous system.

During a stress response, both CRH (Corticotropin-releasing hormone) and AVP (Arginine vasopressin) are secreted. AVP activates the noradrenergic neurons of the Locus Caeruleus/norepinephrine (LC/NE) system and CRH activates adrenocorticotrophic hormone (ACTH) release by the pituitary. The LC/NE system is responsible for the immediate “fight or flight” response, whereas ACTH drives the production of cortisol from the adrenal cortex. When high levels of cortisol are present, a negative feedback loop stops this pathway.

The glucocorticoid hormone cortisol is a major player in the stress response because of its role in temporarily shutting down all long-term metabolic processes to facilitate immediate survival and maintain homeostasis. Cortisol’s main job is to increase gluconeogenesis, decrease insulin sensitivity, reduce growth hormone production, lower thyroid hormones, and inhibit the immune response, while increasing fat and protein mobilization for energy needs.

Acute cortisol secretion by the adrenals during stress mobilizes peripheral amino acids from muscle as well as fatty acids and glycerol from peripheral fat stores to provide substrates for glucose synthesis by the liver. But when cortisol levels are elevated chronically, the functions that are intended for short-term responses to a stress stimulus are prolonged and this leads to changes in body fat distribution and especially increased visceral adiposity (belly fat), which creates several metabolic abnormalities leading to the conditions known as metabolic syndrome.

When cortisol levels increase under stress conditions, DHEA production also begins to decrease through “the pregnenolone steal.” In simple terms, this means that under chronic stress conditions, there is increased production of cortisol while other hormones with a common precursor to cortisol, like DHEA, progesterone, aldosterone, testosterone, and estrogens are depleted. If the stressor does not go away and the stress condition becomes chronic, then a phase of stress adaptation begins, characterized by decreased cortisol production, sometimes known as “adrenal fatigue.” The cortisol production further decreases until the stage when there is complete adrenal failure.


The Bottom Line on Stress & Weight

To summarize, acute stress causes a short term increase in glucocorticoid release, which induces fatty acid mobilization and decreased food intake; whereas chronic stress is associated with sustained cortisol secretion, which leads to redistribution of subcutaneous fat stores to visceral adipose tissue, resulting in central obesity and several metabolic and endocrine abnormalities.

Food consumption also increases during this time as a result of interactions between neuropeptide Y (NPY) and melanocortins as well as leptin and insulin, all of which are consequences of disordered metabolism that goes along with obesity.

Leptin is secreted by adipocytes in proportion to body fat stores and its primary effect is to signal to the brain that there is enough fat in the body, so that food intake can be stopped. Normally, leptin inhibits NPY expression and secretion, thereby controlling the food intake. During chronic stress, excess cortisol enhances the NPY content and induces leptin secretion as well as leptin resistance, thereby inhibiting leptin-¬induced reduction of food intake. Therefore, increased production of cortisol actually induces overeating, worsening obesity despite elevated leptin levels.

Leptin interacts with thyroid hormones, in addition to many other factors, and thyroid hormones may modulate adipokine levels by regulating adipose tissue metabolism – a topic I’ll address in a follow-up blog post. We need to have a better understanding of thyroid hormone abnormalities and their effects on metabolic rate and body fat storage.

In additional blog posts in this series, I will discuss the role of other hormones like estrogens and testosterone in obesity and weight management. It is known that estrogens can influence energy intake and energy expenditure via hypothalamic signaling and play an important role in body weight, fat distribution, energy expenditure and metabolism. Also, obesity is frequently associated with low testosterone levels. Obesity-related hypogonadism is complex and involves many different factors, which lead to changes in body fat mass and further changes in adipokine release and inflammatory pathways.

In conclusion, we must be aware that the adipose tissue is involved in the metabolism of cortisol, and that chronic stress contributes to obesity and leads to a complete imbalance of several other hormones that are impacted by changes in cortisol production. Therefore, hormonal imbalance is a key feature of obesity, and understanding the mechanisms behind this can help people struggling with weight management issues.

Tuesday, June 24, 2014

Advantages and Disadvantages of Testing in Serum, Saliva, Urine or Capillary Dried Blood

Diagnostic testing using body fluids is a cornerstone of modern medicine.  While urine analysis has been used by doctors since the middle ages, blood plasma and serum testing was developed during the last 100 years.  More recently, routine saliva testing for hormones was introduced, followed by commercial testing in capillary dried blood spots.  Dried urine testing has now eliminated some of the disadvantages of liquid urine collections, making this methodology more accessible.

With the innovations in testing methods comes a need to understand which body fluids serve the doctor and patient best in a variety of testing situations.  This is particularly important when testing hormones in patients using supplemental hormones by a variety of administration routes.  The following helps to outline the advantages and disadvantages of each of the commonly-used methods. 

Serum/Plasma - Advantages 

·        Accepted as gold standard testing method by the conventional medical community

·        Wide range of hormone tests available: Ideal for testing peptide hormones

·        Automated with FDA-approved methodology

·        Costs covered by most insurance carriers

·        Familiarity with established levels and ranges

Serum/Plasma - Disadvantages

·        Invasive -sharp needle in arm

·        Stressful -inconvenient to patient-requires driving to blood draw station

·        Phlebotomist required

·        Processing of specimen-centrifugation

·        Shipment-Biohazard labeling and requires cold packs

·        Normal ranges (+/- 2 SD) are too wide-more geared for disease than failing health

·        Difficult to measure multiple times during day due to collection logistics

·        Usually measures TOTAL and not BIOAVAILABLE fraction of hormone in bloodstream

·        Limitations with testing of sex hormones: No distinction between bound and free hormone

·        Cannot be used to measure hormone metabolites

·        Not a valid method for measuring hormones delivered topically -gross underestimation of hormone distribution to tissues

Urine  - Advantages 

·        Non-invasive

·        Simple collection procedure

·        Measures total daily output of steroids

·        Measures steroid metabolites

·        More likely covered by insurance carriers

Urine - Disadvantages

·        Problem with 24 hr urine collections: Inaccuracy in collecting all urine-missed collections

·        Inaccuracy in determining volume of urine collected during 24 hours

·        Up to 40% of 24-hour urine collections are done improperly

·        Results altered by liver or kidney disease

·        Diurnal hormone patterns (cortisol). Inconvenient for assessment of monthly variations (estrogen and progesterone)

·        Expensive and advanced testing technology required for better accuracy

Saliva - Advantages

·        Simple

·        Stress-free

·        Noninvasive (no needles)

·        More convenient than blood testing for health care provider and patient

·        Measures the “unbound” biologically active or free hormone levels

·        Ideal for measuring and accurately monitoring transdermal application of hormones

·        Optimized for multiple collections any time of day/month, any place

·        No special processing (eg, centrifugation, ice-packs) prior to shipment

·        Hormones stable in saliva for weeks

·        Ideal for evaluating cortisol secretion patterns, and balance and flow of estrogens and progesterone.

·        Salivary estriol can be tested to identify women at risk for preterm labor: It spikes approximately two weeks prior to the onset of labor

·        Convenient shipment by regular US mail

Saliva - Disadvantages

·        Restricted to steroid hormones-no thyroid or peptide (e.g. FSH, LH) hormones

·        Technically more challenging: need 10-20x sensitivity-more problematic for hormones at very low concentration (i.e., estrogens)

·        Interfering substances - food, beverages

·        Sublingual use of hormones leads to spurious high test results (direct contamination of the oral mucosa)

·        Problematic for those with poor saliva production

·        Restrictions regarding eating, drinking, make-up and brushing teeth

·        Hormone metabolites cannot be measured in saliva

Capillary Dried Blood Spot - Advantages

·        Convenient-Simple collection procedure

·        Can be collected at remote sites - samples are stable when dried

·        More latitude in collection timing than serum-i.e. night time sampling for cortisol & insulin

·        Dried serum analytes very stable for at least a month at ambient temperature-shipping simplified-allows for international shipment without need for Biohazard Label

·        Wider range of analytes can be tested than in saliva - similar to serum/plasma

·        Results & ranges equivalent to serum/plasma for endogenously produced hormones

·        More accurately reflects tissue uptake of exogenously used hormones than serum/plasma (gross underestimation)

Capillary Dried Blood Spot - Disadvantages

·        Finger-prick with a needle inconvenient for some

·        Not all analytes can be tested in dried blood

·        Sometimes sample contamination problems in patients using their hands to apply topical hormones.

Friday, June 8, 2012

Hormones and Skin Wellness

(Authors: Dr. Sanjay Kapur and Margaret Groves)

Skin health is a major concern, especially in ageing women, which is very good news for the cosmetic and anti-ageing industry. It is no coincidence that the decline in hormone levels as people age parallels the decline in skin properties frequently associated with ageing. A major culprit for the skin thinning, wrinkling, and dryness associated with ageing is the decline in hormones such as estrogen and progesterone in women, and testosterone in men. Hormones are intrinsically involved with processes affecting the maintenance of skin health, such as collagen content, skin lipid levels, elasticity, wound healing, glycoaminoglycan content, and facial hair patterns.
The skin is one of the main targets of estrogen action, and facial skin expresses much higher concentrations of estrogen receptors than the skin of the breast or the thigh. This means that the effects of declining estrogen levels as women progress through menopause are more obvious on the skin of the face than on the skin covering other parts of the body. Reduced availability of estrogen affects skin health in a number of ways: these include wrinkling, dryness, thinning, reduced collagen content, slower wound healing, and loss of elasticity.
Obese men and women often don’t show this deterioration in skin health to the same extent as normal weight people; this is because they maintain higher estrogen levels as a result of increased aromatase activity in fat and skin tissue. Aromatase is an enzyme that converts testosterone into estradiol and androstenedione into estrone, and it is present in large quantities in fat tissue. Estrone and estradiol are therefore found in larger amounts in obese individuals than in normal weight people of the same age. Estradiol is the most potent estrogen, and its main source is the ovaries in reproductive women. Estrone, with weaker estrogenic effects, becomes the more prominent estrogen produced in postmenopausal women as their ovaries stop estradiol production.
Studies of estrogen replacement therapy have shown some improvement in those skin properties affected by low estrogen levels, e.g. increased collagen content, skin thickness, and skin elasticity. Hormone replacement has also been found to increase skin surface lipids, which enhances the barrier function and may prevent dryness. Estrogen also plays a role in maintaining skin glycoaminoglycan content, which retains moisture.
Low testosterone in men is associated with thinning skin. This is thought to be because there is less testosterone available for local conversion to estrogen through the action of aromatase present in the skin. Testosterone replacement has been found to increase skin thickness.
Progesterone has been used in cosmetic skin creams as well as in hormone replacement therapy, and has been found to improve skin thickness and elasticity. Studies have indicated no adverse effects when progesterone is used for this purpose, although some women find that progesterone cream can result in skin breakouts, possibly as a result of other ingredients in the formulation.
Low progesterone levels are thought to increase the impact of androgens on sebaceous glands and body and head hair. This is because progesterone reduces 5-alpha reductase activity, which converts testosterone to its active metabolite dihydrotestosterone (DHT). DHT is the culprit for androgenic side effects in women such as unwanted facial hair growth, which tends to appear with ageing or in androgen excess conditions such as PCOS. In both men and women, excess DHT in the skin contributes to acne, and in the skin of the scalp it is responsible for “male pattern baldness”.
High levels of hormones can contribute to skin discoloration, e.g. the brown patches (“chloasma”) associated with pregnancy or with hormone replacement therapy.
Hormones are important for skin wellness, but caution should be exercised by women and men seeking to reverse skin deterioration by using hormone replacement. Hormonal deficiencies can be identified with minimally invasive laboratory testing and treated with hormone replacement to improve overall health and wellness as well as to mitigate the effects of ageing. However, hormone replacement should be done with appropriate monitoring to ensure that no higher than physiological hormone levels are achieved. It is important to understand that hormones have powerful effects throughout the body. While hormone replacement is not usually recommended solely for cosmetic purposes, proper monitoring of hormone levels in an ageing population can help identify deficiencies that can be resolved with judicious hormone use, which may have the added benefit of improving skin wellness and thereby saving substantial costs in cosmetic treatments.

Wednesday, February 23, 2011

Dr. Sanjay Kapur is putting the spotlight on Dried Blood Spot testing

Click here for my recent interview that was featured on CaribPress

Dr. Sanjay Kapur is a scientist with extensive experience in biomedical research. He has strong interest in health and wellness with an emphasis on heart disease, diabetes and obesity. As Scientific Director of ZRT Laboratory, Dr. Kapur has been instrumental in developing a technology called dried blood spot testing that is being utilized for early detection of major indicators associated with heart health.

CaribPress chatted with the scientist about dried blood spot testing, cardiometabolic syndrome and his journey from India to Canada and to the United States.

CPress: Why biomedical research and when did you decide to venture into the research field?
Dr. Kapur:
I have spent almost twenty-five years in the research field, but research in the area of biomedicine was something that I wanted to do at an early age. My grandparents died of heart failure and diabetes. Genetically I am very likely to develop these conditions and pass them on to my next generation. I do not have symptoms of such diseases right now.

CaribPress: What is dried blood spot testing and does this testing have the FDA (Food and Drug Administration) approval?
Dr. Kapur:
Blood spot testing is a minimally-invasive form of hormone and wellness testing. With a simple finger prick, samples of blood are dropped onto a card which is dried and mailed back to the laboratory. Dried blood spot testing has been used for several decades. Sometimes the FDA approves the sample collection method, sometimes they approve the methods which are used for testing different biochemical markers. Our methods for testing the biochemical markers are FDA approved and the lab supplies that we use as part of our procedures to test these biochemical markers are also FDA approved.

CaribPress: Define and discuss cardiometabolic risk.
Dr. Kapur:
This is my favorite subject. Cardiometabolic is a fairly new term. It involves all the factors that define the overall risks of developing cardiovascular disease. Like age, race, gender, genetics, diet, physical inactivity, obesity, smoking, all these things are responsible for increasing the risk for cardiovascular disease that play a part as much as 10-15 years before you start to see the symptoms. All these things together are what we call Cardiometabolic Risk.

CaribPress: Can you talk about the estimated cost to a patient for dried blood spot testing?
Dr. Kapur:
ZRT Laboratory offers many tests. All of the tests have different prices and depends on the test that is being done. The prices vary depending if someone has insurance or not. For someone who does not have insurance, it is much cheaper to have the tests done in dried blood than the more conventional serum testing. It is more cost effective to test using dried blood spot testing because you don’t have the added cost of going to a phlebotomist or a doctor’s office for a blood draw.

CaribPress: Is dried blood spot testing suited for middle-income or third-world countries?
Dr. Kapur:
Absolutely, actually it is more convenient and suited for those countries. Especially for those people living in remote areas and those people who have absolutely no access to labs with the latest technologies. Because of this dried blood spot testing, they can collect their own samples by a simple finger prick and mail them back to the lab in the regular mail. This method of testing is ideal for people who do not have access to a lab but need to monitor risk factors such as cardiometabolic risk markers.

CaribPress: Can you share something memorable in your journey from India, Canada and to the US?
Dr. Sanjay Kapur:
I received a post-doctoral fellowship and went to French speaking Quebec, where they did not speak English and I did not speak French. I was in India at the time, so the interview was conducted over the phone and I was hired. The fellowship was with Laval University, Chul Research Center and I was there for three years.
When I think back, this journey has been, I would say, tough — a lot of struggles. At the same time, I would say, it was a great learning experience for me. Traveling from India to French speaking Canada (Quebec City), without knowing anyone there; adapting to this new culture, including the weather; working at the hospital, doing research, then moving to California for a very exciting research project that involved designing anti-cancer drugs.

CaribPress: Can dried blood spot testing be used for Sickle Cell and HIV testing?
Dr. Kapur:
ZRT Laboratory does not do HIV or Sickle Cell testing. ZRT testing primarily involves steroid hormone tests, other tests relating to hormone balance, and cardiometabolic risk testing. Other labs are using dried blood spot testing for HIV. For sickle cell, I saw a study that came out in 2006 that screened for sickle cell and the blood spot method they have developed works for that type of screening process.

CaribPress: Talk about the accuracy of dried blood spot testing vs. conventional testing.
Dr. Kapur:
Dried blood spot testing is as accurate as the conventional serum testing. The instruments such as auto analyzers that we use, and the methods that are used to test serum are all the same. The only difference is that the dried blood spot samples are absorbed onto a filter card, so those blood samples have to be first rehydrated and extracted for analysis. So, once they are reconstituted back into liquid form in the lab, we can test them the same way as a conventional test.

CaribPress: Discuss universal testing using saliva and dried blood spot testing.
Dr. Kapur:
At ZRT Laboratory, we have tested more than one million patients using saliva and dried blood spot testing. It is getting very popular. This is coming up as the future of blood testing. There is always going to be a role for conventional serum tests, especially in hospitals where the lab is on hand and where some tests require immediate results, but many risk markers, hormones, and other substances can be tested in dried blood spot or saliva that can be collected at home. People are looking for convenience and lower costs when it comes to taking care of their long-term health.

CPress: What was the impetus for you to be a part of ZRT Laboratory?
Dr. Kapur:
I have been a research scientist with ZRT Laboratory since July 2005. I was back in California and read about Dr. David Zava, the President and founder of ZRT. Dr. Zava had done a lot of research on breast cancer and hormone imbalance. He published articles and books, so I got very interested in hormone imbalance. At the time I was not very much aware of how hormone imbalance can lead to all these diseases and health conditions. So with my background in science I thought it would be a great opportunity for me to join this research team.
Most of the research that I was involved with before coming to ZRT was biochemical research. I thought it would be a great opportunity to join hands and I wanted to help ZRT to conduct research. I wanted people to benefit directly from this research. Most of the research that I had been involved with was mainly biomedical and more academic and it was not research that would directly go to benefit the public. So, after spending so many years in research, I wanted to do something that would directly go on to help people improve their health.
ZRT started this lab by developing a simple and almost non-invasive saliva testing. Later on we developed the dried blood spot technology. We developed this technology to make it easier for testing and convenience to allow everyone to take control of their own health and knowledge — and in particular to be proactive in terms of prevention.

Wednesday, February 16, 2011

Testosterone and Diabetes

A recent interview on Beyond 50 Radio featuring Dr. Sanjay Kapur

Click on this link above and listen to my interview with Daniel Davis on Beyond 50 Radio show where we discussed how Testosterone plays an important role in our lives and possibly has some link with Diabetes.

Low Testosterone has been shown to cause conditions like insulin resistance, metabolic syndrome, central obesity, which further lead to problems like type 2 diabetes and cardiovascular disease. Research studies have shown a link between low levels of testosterone and abnormal lipid levels, increased inflammation, high blood pressure etc. However, it is still not quite clear what comes first- is it that low testosterone levels cause type 2 diabetes or is it that type 2 diabetes result in testosterone level drop. Some research groups have seen improvements in insulin sensitivity, reduction of mid-section obesity, decreased cholesterol levels etc., by testosterone replacement therapy. Some other studies have shown that high doses of testosterone do not have the same benefits as shown by normal physiological levels. Therefore, it is important to monitor testosterone levels using proper testing methods, especially if one is supplementing testosterone to ensure that any supplementation is kept within physiological levels.