From April 2001 issue of Nutrition Science News
by James B. LaValle, R.Ph., C.C.N.
Stress is woven into the fabric of our lives. The stress response was hardwired so we could fight or flee in threatening situations. Today, traffic, falling stock prices, and any number of everyday situations trigger the stress response. Chronic stress, like a tear in the fabric of our homeostasis, can cause health risks.
Hormones and other physiological agents that mediate the stress response have short-term protective and adaptive effects and yet can accelerate pathophysiology when they are over-produced. One such downstream biological effect of chronic stress is weight gain. A number of nutrients and herbs have been identified that regulate and enhance the body's ability to handle stress and its manifestations.
Stress can affect virtually any part of the body and produce physical, mental and emotional symptoms including allergies, dizziness, headache, heart palpitations, environmental sensitivity, impaired coordination, impaired immunity and weight gain. Weight gain is often associated with emotional eating and the too-busy-to-exercise lifestyles of people under chronic stress. But researchers are finding that changes in the body triggered by stress, such as elevated cortisol levels, can cause insulin resistance and weight gain.
Under stress, the body excretes corticotrophin-releasing hormone and adrenalin. This reaction stimulates the release of cortisol from the adrenal cortex. In turn, cortisol, a glucocorticoid, stimulates glucose release into the bloodstream, which, during periods of chronic stress, creates an excessive release of insulin. Insulin, which is part of the endocrine system, is a fat-storage hormone that overrides the stress signal from adrenalin to burn fat. The excess release of insulin gives the body the message to store fat in the abdomen. 
Chronic Stress and Weight Gain
Recent research estimates that 10 to 25 percent of the U.S. population has insulin resistance, or hyperinsulinemia.  These percentages may seem high, but there are several ways to induce hyperinsulinemia. One popular theory is that eating too many carbohydrates causes insulin resistance. Stress could still be behind the carbohydrate theory. Consider the types of food people crave when stressedcarbohydrate-rich and often sugary comfort foods.
Carbohydrates also stimulate production of serotonin, the brain's mood-calming neurotransmitter. Stress drives the carbohydrate cravings. This, combined with the hyperinsulinemic state that many Americans are in, creates the recipe for weight gain. Chronic stress is a big piece to the obesity puzzle that has 50 percent of Americans overweight and another 29 percent obese.
The stress response affects insulin regulation and alters glucose metabolism and fat storage. Obesity is a risk factor for diabetes. But to concentrate on these factors and ignore the function of other organs as well as the hypothalamus and pituitary, thyroid, adrenal and sex glands, is the equivalent of putting a Band-Aid on a bullet hole. The problem is not simply that people are eating too many carbohydrates and thus if they starve their bodies of these foods they will become lean and healthy again. The body needs carbohydrates for brain fuel, fiber and phytonutrients. Rather, the metabolic dysfunction in processing carbohydrates needs to be corrected.
With some 16 million diabetics and another 21 million impaired-glucose-tolerant (IGT) people in the United States, this country is on the verge of a medical crisis.  IGT is a condition in which blood sugar response after a glucose load is impaired, meaning that blood glucose stays around too long. IGT is a risk factor for developing diabetes, and one of the major risk factors for IGT is the presence of intra-abdominal obesity. Stress often triggers many diabetics to lose control of their blood sugar. So the impact of stress and its effects on insulin regulation may over time lead to the development of Type 2 diabetes.
Nutrients to Handle Stress
Stress is here to stay, but there are effective methods for minimizing the damage it can cause. In addition to stress awareness and lifestyle changes, certain dietary supplements, including vitamins, minerals and herbal products, can support the body's ability to handle stress. Researchers are finding that many supplements may help manage and treat short-term stress and stress-related illness.
B VITAMINS, consisting of 11 separate nutrients, help support a healthy nervous system. The B vitamins are generally associated with brain and nervous-system function.
Vitamin B6, pyridoxine, may affect mood by its ability to process beneficial series-one prostaglandins, which have a variety of roles in regulating cellular activities such as the inflammatory response. [7,8] Vitamin B6 is used for treating depression in menopausal women. A study of 630 women with PMS symptoms reported 100200 mg/day vitamin B6 decreased unwanted symptoms. Higher doses provided more benefits. 
Vitamin B6 is associated with serotonin, dopamine and gamma-amino butyric acid (GABA) synthesis.  Dopamine is a neurotransmitter and hormone essential in many body functions, and GABA is an amino acid that works in conjunction with vitamin B6 to help regulate nerve firing. A vitamin B6 deficiency can cause muscle weakness, fatigue, irritability and depression.  The recommended dosage is usually 2050 mg/day, with increases in dosage as warranted, as for PMS symptoms. Depletions can be caused by some prescription medications, including antibiotics  and estrogen-containing medications such as oral contraceptives and estrogen replacement therapy. [13,14] Pharmacists should counsel their patients about medications that may deplete this vitamin.
Vitamin B12 is essential for nerve-tissue metabolism and is necessary for a healthy nervous system because it nourishes the myelin sheath that insulates nerve conduction.  The recommended dosage of vitamin B12 is 100 mcg/day.
Slightly low levels of niacin (vitamin B3) can lead to apprehension, depression, emotional instability, hyperirritability and memory impairment.  Recommended niacin levels vary for a variety of age groups but fall between 25 and 100 mg/day.
Researchers at Massachusetts General Hospital in Boston conducted a study involving 213 subjects. Those with low folate levels were more likely to have melancholic depression and were significantly less likely to respond to Prozac.  The adult recommended daily intake (RDI) of folic acid is 400 mcg/day.
The B vitamins can be deficient in the food supply, so a multivitamin and B-complex supplement is recommended for most people.
DEHYDROEPIANDROSTERONE (DHEA) levels decline under stress as a result of increased cortisol levels.  Many types of physical and emotional stress can cause DHEA levels to dip. DHEA seems to physiologically help the body respond to and regulate stressful conditions, leading researchers to suggest that DHEA could be a therapeutic agent for coping with stress. The normal DHEA dose is 25-50 mg/day, but doses ideally should be individualized because there is no established RDI for this supplement.
VITAMIN C is an important anti-stress antioxidant.  Antioxidants, either from dietary sources, supplements or a combination, reduce the cellular damages associated with oxidative stress. Stress may cause a release of chemical mediators in the body that increase the production of free radicals and subsequently oxidative processes leading to aging and ultimately disease. Antioxidant doses vary depending on the individual's cumulative overall stress levels and biochemical makeup.
Researchers have found that large doses of vitamin C reduce the corticotrophin-releasing stress hormone levels in the bloodstream, which allows the immune system to work more efficiently and helps prevent diseases ranging from colds to cancer. In one study at the University of Alabama, scientists subjected laboratory rats to stress and then gave the animals megadoses of vitamin C (the equivalent of a human taking several thousand milligrams). Vitamin C significantly reduced stress-hormone levels in the rats' blood and also reduced other indicators of physical and emotional stress, including enlarged adrenal glands and changes in the thymus and spleen, which help produce immune cells.  This study indicates high levels of vitamin C can provide significant benefits by enhancing the immune system's ability to combat stress. The most common vitamin C dose is 250 mg/day, but doses up to 2 g/day may be necessary. Aspirin  and oral contraceptives  may cause depletions of this vitamin.
RELORA is a new agent developed by plant-based extraction from the Magnoliaceae plant family. It is particularly effective at reducing anxiety, irritability and nervousness. When it arrives on store shelves, probably later this year, it will be the first natural product since kava (Piper methysticum) to report anti-anxiety benefits.
Relora has the added value of being nonsedating, with potential antidepressant properties. In central nervous system receptor-binding assays, relora was reported to bind to several targets including the serotonin transporter. It does not bind to the benzodiazepine receptors that would cause sedation yet has the relaxing qualities of the benzodiazepine class of drugs in a validated anxiolytic animal model. This study is currently being published in the Journal of Psychopharmacology.
Recently, an independent research firm commissioned by a relora manufacturer administered 50 dietary supplements users with 23 capsules, each containing 200 mg relora, daily for two weeks. The subjects were professional women who stated they lived busy and stressful lives. After the two weeks on relora, 80 percent said they felt more relaxed, and 75 percent said that they had a more restful sleep. This study is not yet published.
KAVA preparations are approved medicines in several European countries for treating nervous anxiety and restlessness. [23,24] Researchers have found kava to compare favorably with benzodiazepine medications for controlling symptoms of anxiety and minor depression while increasing vigilance, sociability, memory and reaction time.  German researchers conducted a double-blind study of 29 people. Those receiving the standardized kava preparation took 100 mg three times/day. The herb caused a statistically significant reduction in anxiety symptoms including feelings of nervousness and somatic complaints such as chest pains, dizziness, gastric irritation, headache, and heart palpitations.  No side effects were reported. Several other studies show kava has positive effects for conditions involving anxiety including PMS and menopausal complaints, as well as for drug addiction and withdrawal. [27,28]
The plant's kavalactones appear to act on the limbic system, in particular the amygdala complex, which is the primitive part of the brain central to emotions and basic survival functions.  Researchers suspect kava may promote relaxation, sleep and rest by altering the way the limbic system modulates emotional processes. Researchers in Germany conducted a meta-analysis and reported that kava was an effective agent for the symptomatic treatment of anxiety. The meta-analysis included double-blind, randomized, placebo-controlled trials of oral kava extract for anxiety. Kava extract had superior effects compared with placebo in all seven reviewed trials. 
The recommended dose of kava for relieving anxiety is 100250 mg, one to three times a day. The product should be standardized to contain 30 to 55 percent kavalactones.
PANAX GINSENG (Panax quinquifolium) has been used historically in Asia for a variety of health benefits, but particularly for its adaptogenic and tonic effects on fatigued or stressed people.  Ginseng has a nonspecific action that increases the body's ability to cope with various stresses, including physiologic, emotional and endogenic (external) toxins, thus reducing susceptibility to illness.
Researchers believe the herb's ginsenosides act at hormone receptor sites, especially in the hypothalamus and pituitary glands. The ginsenosides stimulate adrenocorticotropin secretion, which balances and regulates the hypothalamic/adrenal axis. The recommended dose of ginseng is 200600 mg/day, standardized to contain at least 5 percent ginsenosides. As stress support, ginseng is traditionally used in a regimen of three weeks on, two weeks off. It may take several weeks for a clinical effect to become apparent.
Recommend ginseng with care because it may aggravate certain conditions such as hormonal regulation and hypertension.
ASHWAGANDHA (Withania somnifera) root, also known as winter cherry or Indian ginseng, is an important herb from the Ayurvedic or Indian system of medicine. In that culture, ashwagandha has been used to treat debility, emaciation, and impotence, and to prevent premature aging.  This dietary supplement is used to enhance mental and physical performance, improve learning ability and decrease stress and fatigue. 
Ashwagandha is a general tonic to be used in stressful situations and is especially useful for insomnia, nervousness, and restlessness. The adaptogenic properties of ashwagandha may be attributed in part to its effects on the output of adrenal hormonals. 
The recommended dose of ashwagandha is 450 mg, two to three times daily, standardized to contain 1.5 percent withanolides per dose.
RHODIOLA (Rhodiola rosea), or Arctic root, has been used in traditional folk medicine in China, Serbia, and the Carpathian Mountains of the Ukraine. In the former Soviet Union, it has been used as an adaptogen.
Rhodiola seems to enhance the body's physical and mental work capacity and productivity. It is said to strengthen the nervous system, fight depression, enhance immunity, elevate exercise capacity, enhance memorization skills, improve energy levels and possibly prolong life span. [35-38] In animal experiments, rhodiola extract increased blood insulin and decreased glucagon levels. Rhodiola extracts may help normalize blood sugar levels and decrease insulin resistance, as reported in laboratory animal studies.  This effect is based on the adaptogenic effects of rhodiola, including actions on adrenal hormones that help regulate insulin levels.  Current accepted practices suggest 50100 mg twice daily, standardized to contain 1 percent salidrosid or 40 to 50 percent phenylpropenoids per dose.
HOLY BASIL (Ocimum sanctum), also known as tulsi or sweet basil, is widely used in cooking and as a medicinal herb in Eastern and Middle Eastern countries. A holy basil extract has been reported to combat stress in laboratory animals by balancing the blood corticosteroid levels.  Current accepted practice recommends holy basil doses of 400 mg daily, standardized to contain 1 percent ursolic acid per dose.
Stress is a normal part of life. What really matters are how much stress, what kind of stress, and ultimately how each individual handles the stress they face. Long-term stress takes a physical toll because the body tries to find ways to adjust to metabolic changes. If lifestyle modifications do not workleaving a stressful job, exercise, meditationthen biochemical and nutritional factors may be useful. Pharmacists can educate their customers about nutritional therapy and have a lasting influence on their health.
James B. LaValle, R.Ph., C.C.N., is adjunct associate professor at the University of Cincinnati School of Pharmacy and co-founder of Intramedicine Inc. His next book "3  Cracking the Metabolic Code: Nine Keys to Optimal Metabolism" will be published later this year.
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