Natural Compounds for Estrogen Metabolism Support

Recall from the last post that we looked at how the liver plays a vital role in metabolizing estrogens. I left you with the thought that those important pathways which so often go awry can be modified with specific compounds from nature. “Although the estrogen receptor is required for a cell to respond to an estrogenic stimulus, the nature and extent of that response are determined by the proteins, pathways, and processes with which the receptor interacts.” Connections and Regulation of the Human Estrogen Receptor, Dean McDonnell and John D. Norris

This means that factors other than the presence or absence of estrogen influence the response of the estrogen receptor and the cell. These factors are what make up the chemical environment in and around the cell, and can be impacted by nutritional factors. The way estrogen receptors create chemical messengers that relate to other receptors is called “cross-talk,” and it would make sense that this “cross-talk” is influenced by nutrient status.

We’ll look at a few of the natural compounds in this post that positively affect estrogen metabolism.

Indole-3-CarbinolIt has been demonstrated convincingly that Indole-3-Carbinol (I3C) from cruciferous vegetables increases the healthful 2-OHE estrogen pathway and decreases the harmful 4-/16-OHE estrogens.

“Indole-3-carbinol (I3C), a compound occuring naturally in cruciferous vegetables, exhibits a potent antitumor activity via its regulation of estrogen activity and metabolism... These results further suggest that antitumor activities of I3C are associated not only with its regulation of estrogen activity and metabolism, but also its modulation of ER transcription activity.” J Nutri 130:2927-2931(2000)

“It has been shown that it induces CyP450 1A1, increasing 2-hydroxylation of estrogens, leading to the protective 2-OHE1, and also decreases CyP 1B1 sharply, inhibiting 4-hydroxylation of estradiol, thereby decreasing the formation of the carcinogenic 4-OHE1. …it has also been shown to be effective against HPV-mediated tumors in human patients.” Ann Ny Acad Sci889:204-213(1999)

“These results indicate that anti-invasion and antimigration activities of I3C occur via estrogen-independent and estrogen-dependent pathways. …current finding is the first demonstration that I3C can activate the function of invasion suppressor molecules associated with the suppression of invasion and migration in breast cancer cells. Thus, clinical application of I3C may contribute to the potential benefit for suppression of breast cancer invasion and metastasis.” J Mol Med78:155-165(2000)

Supplementation with I3C has shown promise in the literature:

• Supplementation with concentrate (400 mg/d) promotes 2-Hydroxylation and improves 2-OH:16-OH ratio. Michnovicz JJ, et al, J Natl Cancer Inst, 89(10):718-20, 1997.
• May also reduce 4-Hydroxylation. Bradlow HL, et al, Ann NY Acad Sci, 889:204-13, 1999.
• 300-400mg/d promises to be a chemopreventive agent. Wong et al., J Cell Biochem Suppl 1997;28-29:111

I3C has also shown to positively influence gene expression! Recall that estrogen metabolism occurs in specific liver pathways. The CYP450 1A1 pathway forms 2-OH, and the single nucleotide polymorphism (SNP) Msp 1 impairs 1A1 function. I3C, however, improves estrogen metabolism even in the presence of the polymorphism! Bartsch et al., Carcinogenesis 1999;20(12):2209, Taioli et al., Cancer Detection and Prev1999;23(3):232

The CYP450 1B1 pathway, however, forms the 16-OH hormone, and the SNP V432L increases the function of the 1B1 pathway. I3C inhibits 1B1 even in the presence of the SNP! Bradlow et al., Ann NY Acad Sci 1999;889:204

We’ll look at more natural compounds for healthy estrogen metabolism in the posts following.

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Related Formula: Meta I3C

When Estrogen Metabolism Goes Awry (And How to Fix it)

I’ve heard so many positive reports on the power of the Metagenics formula for estrogen metabolism, I thought that it would be time well spent to talk about estrogen in the next few posts.

How Estrogen is Metabolized
The majority of estrogens are detoxified in the cytochrome (CYP) P-450 1A1 phase 1 liver process known as hydroxylation. Fifty percent of all estrogen is metabolized through the catechol-2 (C2) position, creating the weaker 2-hydroxyestrone catechol, whereas the rest is metabolized through much stronger estrogenic pathways known as the C4 and the C16 positions (via the cytochrome 1B1 pathways), which create the 4-OH and 16-OH hormones.

Data is piling up that the 2-OH hormone is protective, whereas overproduction of the 4 and 16-OH estrogens heighten the risk of cancer.

“The expanding data indicates that 2-OH estrone is anticarcinogenic. In every experimental model in which 2-OH was increased, protection against tumors was achieved. Correspondingly, when 2-OH was decreased, an increase in cancer was observed.” J Endocrinology 130:S239-S265 (1996)

“4-OH-E1 and 16-OH-E2 are considered carcinogenic.” Gruber et al., NEJM Jan 31,2002; 346(5):340

“In a study of 10,786 women it was found that the ratio of 2-OH to 16-OH estrone was a very sensitive indicator of breast cancer risk. The higher the ratio of 2:16 OH, the lower the incidence of breast cancer.” Epidemiology 11:635-640 (2000)

The question then, how does the body shift its load of hormone metabolism toward the unfavorable 4 and 16-OH pathways and away from the healthier 2-OH pathway?

“…environmental factors enhancing aromatase activity might result in high tissue concentrations of E2 that would likely be sufficient to serve as substrates for CYP1B1… for formation of catechol metabolites that are estrogenic and which, upon further oxidative metabolism, form genotoxic species at levels that may contribute to estrogen carcinogenesis.” J Nat’l Can Inst Monographs #27:95-112 (2000)

In short and simple terms, environmental factors including toxic pollution and chemically-altered food can enhance the enzyme aromatase, which serves as a precursor to various hormones, including testosterone. This jacked-up aromatase activity shifts estrogen metabolism in the liver toward the cytochrome 1B1 pathway, which is the one that makes more of the 4 and 16-OH estrogens.

Phase 2

After the phase 1 processes in the liver are complete, the phase 2 pathways complete the process of hormone metabolism via the methylation, glucaronidation, and conjugation pathways. Methylation, for example, is protective because once the hormones are hydroxylated in phase 1, they are then either methylated and excreted, or in the case of faulty methylation, they are oxidized to quinones.

“Methylation (of 2-OHE2 and 4-OHE2) by catechol-O-methyltransferase (COMT) is the principal means of catechol estrogen deactivation in the liver and other tissues.” Toxicol Appl Pharmacol 162, 115-123 (2000)

“Catechol-O-methyltransferase (COMT) is a phase II enzyme that deactivates catechol estrogens into non-genotoxic methyl ethers that can be easily excreted by the body.” Carcinogenesis vol.24 no.4 pp.681±687, 2003

There is a Reason for all this Biochemistry
The reason for all this biochemistry is to drive home some important take-aways: The favorable metabolic pathways can be influenced by diet and supplements! CYP 450 and COMT activity can be influenced by diet and supplements! The favorable metabolic pathways can be influenced by diet and supplements!

Where diet is concerned, the damaging effects of upregulated aromatase activity can be improved by eating less sugar, as insulin will tend to produce more adipose tissue, and fat cells contain more aromatase which in turn will produce more estrogen from testosterone. Losing weight and improving the diet can positively influence estrogen metabolism!

Xenoestrogens from the environment, likewise, contribute to the estrogen pool and inhibit normal estrogen metabolism. Thus, a detoxification program might be in order.

Where specific supplements are concerned, pathogenic gut bacteria deconjugate detoxified estrogens, allowing for their reabsorption. So probiotic bacteria can help to complete the process of estrogen conjugation and elimination in the gut. But it goes way beyond that. There are specific macro and micronutrients that can greatly influence estrogen detoxification for the better and improve hydroxylation, methylation, etc in the liver.

That is the subject of the next post. Stay tuned.

New Study Finds Mushrooms Slash Breast Cancer Risk

New research has concluded that regular consumption of mushrooms can decrease a woman's risk of breast cancer by two thirds.

Scientists from the University of Western Australia in Perth conducted a study on 2,018 Chinese women, half of whom had been diagnosed with breast cancer. After adjusting for known cancer risk factors such as obesity, smoking, lack of exercise and lower education level, the researchers found that women who ate at least 10 grams of button mushrooms per day were 64 percent less likely to develop breast cancer. Women who ate dried mushrooms regularly also significantly reduced their risk of developing the disease, although not by as much.

The study was published in the International Journal of Cancer.

This is not the first time scientists have found evidence of mushrooms' cancer-fighting properties. Numerous studies have found that mushrooms may suppress the body's production of the sex hormone estrogen, much like the breast cancer drugs known as aromatose inhibitors. High estrogen levels are a well-known risk factor for breast cancer. Mushrooms have also been found to strengthen the body's immune function, stimulating the all-important T-cells and killer cells, and thus block tumor development. Mushroom extract has been shown to stop the growth of breast cancer cells, sparking an ongoing study evaluating whether taking mushroom extract twice per month can prevent a recurrence of the disease.

Researchers believe that certain mushrooms work by blocking the action of an enzyme known as AKT, which plays a role in controlling cell growth. Prior studies have suggested that mushrooms hamper the activity of skin, lung and prostate cancer cells. They reduce accelerated cell growth and block the development of blood vessels that feed tumors.

Some of the most medicinal of the mushroom family include reishi, shiitake, Fu-Ling, Turkey Tail, Oyster mushrooms, cordyceps, and maitake. These can be obtained individually in supplement form or in combination.

Acid Reflux

Acid blocking drugs are some of the most prescribed medications in the country. Aside from those using prescription medications, forty percent of adults self-medicate with antacids and other OTC medications.

But inhibiting stomach acid may not be such a good thing.

Hydrochloric acid (HCl) plays many important physiological roles. Aside from its obvious role and breaking down solid food that can be passed into the small intestine, HCl also assists in protein digestion, facilitates the absorption of minerals and B-vitamins, and stimulates pancreatic enzymes and bile secretion. HCl also protects against orally-ingested pathogens and is the first line defense against infections, helping prevent bacterial and fungal overgrowth of the small intestine.

In short, blocking acid production can set the stage for a variety of maladies related to nutrient deficiencies and bacterial infestations. Yet these drugs are first line therapy for acid reflux and represent the third highest selling category of OTC medications. Thus, exploring alternative methods is paramount.

Understanding Stomach Physiology
When food is present in the stomach, the parietal cells go to work to secrete pepsin and HCl. The stomach then proceeds to gently churn up the mix until the food is pulverized into a soupy consistency that can be passed into the small intestine for extraction of nutrients into the bloodstream. During this process a signal is sent to the esophageal sphincter muscle at the top of the stomach and it closes tight, preventing access of the stomach contents into the esophagus.

The length of time that this process takes will vary depending on the size of the meal, but even with larger meals it usually takes a couple of hours at the most if everything is in order.

When Things Go Awry
A number of different factors play into why stomach function goes awry and people begin to experience acid reflux.

For one, the quality of nutrition is huge. The parietal cells of the stomach are very dependant upon certain nutrients, especially zinc, for their normal function, and when nutrient deficiencies are present the production of stomach acid can be affected.

Stress is also a factor, as chronic stress has been implicated in causing sometimes catastrophic changes in various functions of GI health.

Additionally, sometimes there is literally a structural malfunction of the esophageal sphincter muscle that sometimes requires surgery to repair.

For this post we’ll focus our attention on stomach acid production.

Is the Burning Because of Too Much Acid, or Too Little?
The common medical mindset pertaining to acid reflux is that too much stomach acid causes acid reflux. I suppose sometimes that is true, but more often than not it probably isn’t true. The reason is that if there is a malfunction in the stomach acid secretion process such as a nutrient deficiency, then two things can happen: 1) The mechanism that is supposed to signal the esophageal sphincter to close off after the parietal cells begin secreting acid is weak or sometimes broken altogether since there is too little stomach acid to initiate it. Thus, the sphincter remains relaxed and acid can backwash up into the esophagus, which of course is very uncomfortable. 2) Because of too little stomach acid to break down food properly, food can sit in the stomach for hours and putrefy, thus causing build up of gases in the stomach that pushes the acids to the top of the stomach and causes reflux.

In short, acid reflux can very often – perhaps more often than not – be caused by not enough stomach acid, not too little of it.

An Alternative Solution
A simple solution to the problem of acid reflux is to give MORE acid, not suppress what little you have. HCl and pepsin can be provided in tablet form and can be used to supplement one’s own production of stomach acid so that food is broken down properly, gas and bloating is reduced, and reflux is controlled.

Given the current trends in the reduction of stomach acid production with age, it stands to reason that most people suffer from having too little instead of too much. Research shows that by the time the average person is 40, stomach acid production is reduced by 50% compared to age 20. And by the age of 60 the production is reduced by two thirds as compared to age 20. Timiras PS. Aging of the gastrointestinal tract and liver. In: Timiras PS, ed. Physiological basis of aging and geriatrics. 2nd ed. Boca Raton: CRC Press1994:247-57.

Likewise, the use of a novel agent known as zinc-carnosine has been shown to be remarkably effective in treating acid indigestion and diminishing the presence of a bacteria called, Helicobacter Pylori, which has been implicated in stomach ulcers.

Symptoms of Low Stomach Acid
-Bloating or distention after eating
• Diarrhea or constipation
• Indigestion
• Excessive belching, burping and/or bloating
• Flatulence after eating
• Sense of fullness during and after meals (prolonged)
• Poor appetite, disinterest in food
• Offensive breath
• Bad taste in mouth
• Partial loss of taste or smell
• Difficult bowel movements
• Difficulty swallowing
• Unintentional weight loss
• History of anemia, unresponsive to iron
• Spoon shaped nails
• Sores in corner of mouth
• Smooth tongue

Section 1, Part A of the Health Appraisal Questionnaire is a quick and easy way for practitioners to diagnose possible stomach acid issues.
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Related formulas:
Metagest
Zinlori 75

Stressed and Tired: Adrenal Support part 4

In this final installment of my adrenal stress series, let’s take a look at low cortisol and the end stages of adrenal fatigue.

Recall that in the first stages of adrenal stress the cortisol is upregulated and the patient presents with anxiety, irritability, nervousness, and an inability to cope with stress. When that condition goes on long enough, the adrenals eventually become very fatigued and cortisol drops off to below normal, and sometimes flat lines altogether. When that happens, severe and prolonged fatigue sets in, and along with it a whole host of other related maladies, such as low libido and reproductive problems, muscle aches and inflammation, low immunity, and allergic reactions, to name just a few.

Nutritionally, these patients need aggressive support in nourishing the adrenal glands directly with adrenal extract, B-vitamins, magnesium, etc, as discussed in previous posts. But the plant kingdom also offers some very powerful options for supporting the entire HPA axis in these patients.

Of note are four herbs in particular: Rhodiola, Cordyceps, ginseng, and Licorice.

Rhodiola
Also known as “Arctic Root,” Rhodiola is a flowering plant that grows at high altitudes in regions of Eastern Europe and Asia. In Russia, rhodiola has been used for centuries to cope with the cold Siberian climate and stressful life, where it was valued for its purported ability to promote energy and stamina, enhance mental and physical performance, and prevent fatigue. Russian scientists conducted a great deal of anti-stress research on rhodiola, who categorized is as an adaptogen due to its ability to increase resistance to a variety of chemical, biological, and physical stressors. Based upon the impressive results of this research, rhodiola became widely used by Russian athletes and cosmonauts to help maintain energy levels, promote a healthy mood, and increase attention span and physical performance.

Cordyceps
Cordyceps is one of the most valued medicinal plants in Chinese medicine, where it is traditionally used as an adaptogen to support vitality, as a lung and kidney tonic, and to stimulate libido. It has similar properties to those of ginseng, such that it is traditionally used to strengthen the body after exhaustion. The wide spectrum of activities of cordyceps in quite impressive, with observations of beneficial effects on the respiratory, renal, hepatic, cardiovascular, immunological, and nervous systems, as well as glucose and lipid metabolism.

Asian Ginseng
Ginseng root is a highly valued tonic in traditional Chinese medicine, noted for its ability to stimulate mental and physical activity, enhance stamina and prevent fatigue, and increase resistance to stress. According to tradition, the individual who will benefit from ginseng is run down and has exhausted his/her reserves. Although the exact mechanisms have not been determined, animal and human studies suggest that ginseng may influence the activity of the HPA axis in multiple ways. These mechanisms may include 1) promoting the synthesis of corticosterones by increasing levels of cyclic adenosine monophosphate in the adrenal cortex, 2) influencing feedback mechanisms of stress hormone receptors, 3) stimulating adrenocorticotropic hormone (ACTH) in the pituitary gland, 4) increasing HPA sensitivity to glucose corticoids, and 5) inhibiting cortisone-induced adrenal and thymic atrophy. Through these actions, ginseng appears to promote a healthy stress response by helping to balance HPA axis function.

Licorice

Licorice is an herb with an unparalleled reputation for promoting health and longevity, and it has gained a reputation for strengthening the body during periods of stress. This perennial herb is native to southern Europe, Asia, and the Mediterranean, and was used by ancient Chinese, Egyptian, Greek, and Roman cultures. Currently, licorice is not only one of the most frequently used herbs in traditional Chinese medicine, but it is one of the most popular and widely used herbs in the world. Licorice is well known for its ability to influence adrenal hormone levels. The adrenocorticoid activity of licorice is associated with glycyrrhizic acid and glycyrretinic acid. These activities have ben reported to bind to both glucocorticoid and mineralcorticoid receptors, possibly displacing endogenous steroids and thus contributing to an increase in cortisol availability. Additionally, research suggests that glycyrrhizic acid and glycyrretinic acid increase the half life of cortisol by inhibiting its enzymatic breakdown in the kidneys and liver, thus it is an excellent choice for those with low cortisol production.

Licorice also demonstrates immunosupportive, immunomodulatory, hepatoprotective, and detoxifying qualities. In addition, licorice is traditionally and widely used to promote the health of and soothe mucous membranes of the respiratory and digestive systems.

While the best method of dealing with stress is to get out from under it, that is not always possible in the fast-paced Westernized culture. However, nutritional support of stress defense mechanisms is an excellent way to prevent and treat stress-related conditions.

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Related formulas:

Adreset

Licorice Plus

Managing Stress-Related Disorders, Part 3: Adrenal Extract

The endocrine system is like a house of cards. It is an interwoven system where all the individual components are interdependent. It is therefore difficult to affect one area of it without tripping off the whole thing. That is important in understanding adrenal fatigue, because the stress on the adrenals could actually be caused by another malfunctioning system, such as that of blood sugar metabolism. But that is a discussion for another day.

In the last post I talked about hypercortisolemia, where the cortisol is in a chronic state of elevation and the patient manifests with anxiety, restless sleep, irritability, etc. When that state goes on long enough, soon the adrenal glands begin to fatigue and the cortisol drops off. Since we need a certain amount of cortisol for normal function, a lack of it can cause terrible fatigue, low libido, a loss of drive and motivation, and eventually inflammation.

For this post, let’s focus on treating low cortisol with the use of adrenal glandulars.

Glandular Therapy for Adrenal Support
The concept of using animal tissues in treatment of disease and support of health is a controversial one in medicine, with opinions ranging from useless to miraculous. On the one hand, we have thyroid hormones, insulin, and estrogens, for example, which are used routinely. On the other hand, we have extracts of tissues from glands such as adrenal, pancreas, pituitary, thyroid, etc, which can be taken orally to help support those same tissues in humans.

The argument against using glandulars as supplements is that it is simplistic to think that eating an animal’s glands would help strengthen one’s own like glands. From a medical perspective, one should be able to measure the hormone activity of any substances used and monitor their effects in the body. Glandulars, however, are usually measured by the amount of the actual glands present, but we do not really know what they do. Further, since these glands are broken down into their basic nutrients in the digestive tract, many believe that they would not necessarily go directly to improve one’s own glands.

The pro argument is that it is likely that the basic components of those gland tissues may offer the precursor substances that our own bodies and glands can use to enhance their functions. And there may be hidden factors that may offer some benefit. The glands, like foods, supply basic nutrients, such as amino acids, fatty acids, vitamins, other active substances, and a potential "life force," for lack of a better term, where a drug will not. Some evidence from radioisotope studies suggests that glands, when eaten, do in fact influence the function of the human glands.

In modern medicine, glandular therapy began in the late nineteenth century when physicians suggested that their patients eat the animal parts, usually from cows, that corresponded to the weak areas of their own bodies. So people began eating brains, hearts, kidneys, and so on as part of their medical treatment.

Actually, glandular therapy began much earlier than this, as the ancient Greeks and Egyptians used it following their basic premise that "like heals like." Technology and medical endocrinology evolved this therapy by isolating specific hormones at the source of the glands’ activities (just as we extracted the active pharmaceutical drugs from whole plants). These new drugs are more potent, but they also have more potential for dangerous side effects than the whole glands.

For example, desiccated thyroid gland was first utilized in the late 1800s to help people with goiter and low thyroid function. Then thyroxine (T4) was isolated and used, but many doctors still preferred the whole gland as it was felt to be better absorbed and utilized by the body. Later, the other thyroid hormones, triiodothyronine (T3) and calcitonin were discovered, but these were always part of the whole gland. Today, both individual synthetic hormones and measured active thyroid tissue are used to support or replace thyroid activity.

In the early 1920s, insulin was isolated by Sir Frederick Banting and Charles H. Best, who received the Nobel Prize for their discovery. Insulin has been a lifesaver for many diabetics, but it is also a potentially dangerous drug because it has such a narrow range of safe uses. Overdoses can cause very low blood sugar and shock. Insulin is destroyed in the gut, so it must be injected. It is possible that when extracts of pancreatic tissue are used as supplements, as with other glands, certain molecules protect the active hormones from the digestive juices, and some of these substances actually get into the body. The whole pancreas gland, which had previously been used, is certainly safer than insulin, but pancreas itself is not thought to be strong enough to treat diabetes once it is established.

In the case of treating conditions associated with adrenal fatigue, adrenal glandulars are often suggested for people who experience fatigue, stress, environmental sensitivities or allergies, infections, and hypoglycemia. The symptoms that come from low blood sugar are probably more related to adrenal than to pancreas, and supporting the adrenals with freeze-dried adrenal at 50–100 mg twice daily, along with other stress-supporting nutrients, such as the B vitamins, may be helpful. For extremely low cortisol, some physicians find it useful to super-dose with as much as a gram of adrenal glandular with B-vitamins for a period of a few days to kick start the adrenals back to optimal function. This approach would not be recommended for someone who has elevated cortisol, but could be very helpful for those who are experiencing the overwhelming symptoms of low cortisol.

In my 15+ years in this industry, I have come to rely heavily upon third party data, but have also learned to not rule out clinical experience even when research is lacking. And the clinical experience of hundreds of physicians points to the fact that adrenal extracts works extremely well in treating adrenal fatigue and the associated maladies.

In the next post I’ll introduce you to some other very powerful options from the plant kingdom in supporting the HPA axis and sluggish adrenals.

Managing Stress-Related Disorders, Part 2: "Stressed and Wired"

Americans as a lifestyle maintain a state of hyper arousal of the adrenal glands. In this condition the cortisol and other stress molecules are upregulated. This state of arousal is an important survival mechanism for emergency situations, but chronically high cortisol is catabolic and sets that stage of all manner of dysfunction and disease.

For starters, high cortisol causes a chronic state of agitation, irritability, anxiety, nervousness, and even panic attacks. This can affect sleep patterns, increase cardiovascular risk factors, decrease the libido, impair the memory and learning patterns, cause muscle wasting, and reduce reproductive function, to name just a few.

Nutritional Management of Elevated Cortisol: B-vitamins
The B-vitamin family is important in any adrenal support program, because the B-vitamins help to support the neurological system and the adrenal glands themselves and change the way a patient interprets the stress. Folate, for example, ranging from as little as 200 mcg to as much 15 mg, has shown anti-depressive effects. Folate and B12 deficiency has long been associated with depression. B-vitamins are involved in norepinephrine, dopamine, and serotonin synthesis, and are coenzymes in the synthesis of adenosylmethionine (SAM), and shown to have antidepressive properties.

One note of interest is that folate in the form of folic acid does not cross the blood/brain barrier. There is only one form of folate that does, and that is the end metabolite of folate metabolism, 5-methyltetrahydrofolate (5-MTHF). It is important that any B-vitamin complex you are using for depression and/or anxiety contains this form of folate.

Studies in animals have shown that a deficiency in another important B-vitamin, pantothenic acid (B5), mimicked metabolic changes seen in adrenal insufficiency. Administering B5 increases the production of corticosteroids. In humans, it normalized the response to ACTH and deficiency led to reduced resistance to stress.

Vitamin B6 is also essential, in that it is important to the metabolism of most amino acids. It also converts tyrosine to dopamine for epinepherine synthesis and protects from homocystiene overproduction. A derivative, homocystiene lactone, can inhibit ACTH release.

Likewise, the B-vitamin, myo-inositol, has been shown to be remarkably effective by itself in the treatment of panic attacks, obsessive compulsive disorder, and depression. In one study comparing the effects of myo-inositol against the drug, Fluvoxamine, for panic disorder, the myo-inositol “reduced the number of panic attacks per week by 4.0 compared with a reduction of 2.4 with Fluvoxamine. Nausea and tiredness were more common with Fluvoxamine.” J Clin Psychopharmacol 2001 June;21(3)335-9

The American Journal of Psychiatry reported that inositol in doses of 6g/day and 12g/day “is a potential treatment for depression in both open and double-blind placebo controlled trials.” Double-Blind, Placebo-Controlled, Crossover Trial of Inositol Treatment for Panic Disorder, J Benjamin, et al, Am J Psychiatr, 152: 1084-1086

Myo-inositol is especially beneficial in overall nervous system function because it is an important naturally occurring component of cell membranes. Myo-inositol plays a major role in cell signaling by functioning as a precursor of an intracellular second messenger system. This system is especially important in the brain. For example, serotonin and norepinehprine receptors are linked to the inositol second messenger system.

Magnesium
Another micronutrient deficiency that can have an adverse effect on the stress response is magnesium. According the Journal of the American College of Nutrition, magnesium deficiency intensifies adverse reactions to stress. Such reactions are mediated by excess release of catecholamines and corticosteroids, and low magnesium and calcium levels increase the release of stress hormones, which further lower tissue magnesium, creating a snowball effect. Likewise, magnesium plays a role in maintaining healthy levels of the myo-inositol pool in the body.

Herbal Support for Stressed and Wired
A revered “vitalizer” and rejuvenative tonic in Ayurveda (Charaka Samhita 1000 BC), the herb ashwagandha has been traditionally used for stress tolerance, vigor and stamina, convalescence, nervous exhaustion, fatigue, geriatric debility, physical and mental stress, and insomnia, while no side effects have been reported.

Another remarkable rejuvenating herb, holy basil, has anti-stress activity, including a normalizing affect on the CNS. It has been shown to reduce incidence of gastric injury induced by cold stress and restraint stress. It also inhibits the lipoxygenase and cyclooxygenase prostaglandin pathways, antagonizes histamine, and decreases acid and pepsin output, enhances gastric mucosal strength, and helps normalize the stress-response.

Ayurvedic literature attributes a “non-specific increased resistance”to the herb bacopa (also known as brahmi), and has been traditionally used to revitalize the nerves, brain cells, and the mind. It helps to strengthen the adrenals and purify the blood, and in animal testing it improves adaptations in sensory, motor, and motivational systems. In humans bacopa exhibits beneficial effects on anxiety and mental functions (mental fatigue). The effects on the CNS may be mediated through stimulation of gamma-aminobutyric (GABA)ergic and cholinergic systems.

What to Use When
A B-vitamin complex featuring the active form of folate, and/or a high-potency B5/B6 formula is foundational for stress protection and the early signs of adrenal stress, typically presenting in the form of anxiety and high cortisol levels. Additionally, an herbal complex featuring bacopa, ashwagandha, and holy basil can be added for complementary support in helping to rejuvenate the body and support the CNS. If the anxiety becomes severe, one should consider the use of a myo-inositol and magnesium complex to control anxiousness and regulate the mood.

There are a number of other herbal-based remedies as well for the other stages of stress, and we will discuss those in the next post.

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Stress formulas to consider:

Glycogenics

Cortico B5B6

Cenitol

Exhilarin