The mental health of society is deteriorating. Mood disorders such as anxiety and depression impact the world on a scale far greater than is generally recognized. According to the World Health Organization (WHO), Geneva, Switzerland, 450 million people worldwide are affected by mental, neurological or behavioral problems at any given time. As a result, this has created a problem of epidemic proportions.

The Global Burden of Disease study, conducted by researchers at Harvard University, Cambridge, MA, found mental disorders, including suicide, ranked second in societal burden, behind only cardiovascular conditions in developed nations. Further, projections show that psychiatric and neurological conditions could increase their share of the total global disease burden by almost half, from 10.5% of the total burden to almost 15% in 2020.


Break Down
Mental and behavioral disorders create devastating emotional and financial tolls on individuals, families and communities. According to estimates from The National Institute of Mental Health (NIMH), Bethesda, MD, the direct (clinical treatment and services) and indirect (lost/diminished productivity and premature mortality) cost of mental disorders is roughly $160 billion annually in the U.S. alone. An estimated 22% of Americans age 18 and older-about 1 in 5 adults-suffer from a diagnosable mental disorder in a given year. According to the 1998 U.S. Census estimates, this figure translates to 44.3 million people. In addition, 4 of the 10 leading causes of disability in the U.S. are mental disorders, which include major depression, bipolar disorder, schizophrenia and obsessive-compulsive disorder. It is also common for people to suffer from more than one mental disorder at a given time.

The NIMH estimates that approximately 19 million American adults suffer from depression alone, with nearly twice as many women affected as men. However, women are more likely to admit their condition and seek treatment, while men stay in denial more often and avoid treatment. In addition to depression, many Americans are also dealing with increasingly high levels of stress and anxiety, which are often precursors to depression. The NIMH estimates that approximately 19 million Americans adults suffer from anxiety disorders.

"We live in a maximum overdrive society surrounded by a frenetic pace of life, unhealthy fast food diets, environmental pollution and mounting financial and social pressures including alienation, isolation and fragmented family lives," commented Zakir Ramazanov, president and CEO, National BioScience Corp., Warwick, NY. "Modern stress has become unnaturally intensified in ways that undermine our capacity to adapt and remain healthy."

As the rates of stress and depression increase, they continue to wreak havoc not just on the mind, but on the body as well. Both stress and depression form a complex impact on human health as the two are inextricably linked to a wide array of health conditions including eating disorders, obesity, diabetes, heart disease, hypertension, sexual disorders, osteoporosis, immunity and sleep disorders.

Despite the devastating effects of mental health disorders, they have for the most part been ignored, confined to the shadows of society, unlike physiological health conditions such as heart disease and cancer. The reason mental disorders have been marginalized is the result of the negative stigma that is associated with mental illness. However, a statement released by the American Psychiatric Association (APA), Arlington, VA, said that growing public awareness of the burden and costs of mental illness and of the gains being made through research are contributing to increasingly enlightened policies for the organization and financing of mental healthcare, which last year led to President Bush identifying three obstacles that prevent Americans from getting the mental healthcare that they need. These include "stigma, unfair treatment limitations and financial requirements under health insurance plans and a fragmented mental health service delivery program." As a result, the statement from the APA went on to say that the President formed the New Freedom Commission on Mental Health, which recommended strategies for redressing these and other barriers to high quality to provide appropriate mental healthcare for all Americans who need it.


Putting the Pieces Together
The first line of defense for most people with stress and depression consists of antidepressant medications such as Zoloft, Paxil and Prozac. The evidence to date shows no signs of preventing stress and depression and these drugs have been effective against major depressive episodes. However, the growing awareness of the serious side effects of prescribed antidepressants has encouraged people to look for alternatives to maintain a healthy mood in less severe cases.

According to Julie Thibeau, director of sales and marketing, NutriScience Innovations, Fairfield, CT, there has been a growing focus on mood enhancement in the dietary supplement industry. "With the changing times, the state of the economy and a constant reminder of war, many people are looking to reduce their levels of stress and ease tension," she said. "There has always been a stigma associated with pharmaceuticals, or prescribed antidepressants. Consumers are looking for natural alternatives that work, are readily available and do not cause any negative side effects."

In terms of demographics, Virender Sodhi, M.D. (Ayurved), N.D., Ayush Herbs, Bellevue, WA, said that mood-enhancing ingredients have a broad appeal. "Students, executives, managers, entrepreneurs, housewives and anyone in general experiencing stress are potential users of mood-enhancing ingredients," he said. "Mood-enhancing ingredients have become hot sellers as Americans age and continue to meet the demands of stressful living conditions."

However, Mr. Ramazanov said that the industry has to do a better job of educating the public. He said most consumers are not aware of the devastating impact mood disorders have on their health. "That is why today's consumer is looking for natural products for conditions such as weight management and sexual function, rather than for stress and depression management," he said. "The dietary supplement industry is doing a poor job of educating consumers. It is important to provide true and clinically proven scientific information related to the prevention and treatment of chronic stress, depression and the handling of mood disorders."


The Serotonin Connection
When it comes to depression, depletion of the neurotransmitter serotonin in certain synapses of the brain is most often implicated as the root cause of disorders of the central nervous system. Don Stanek, director of sales, Linnea, Locarno, Switzerland, explained, "When levels of serotonin drop too low, this leads to a number of symptoms ranging from anxiety, obsessive behavior, insomnia and depression. As a result, something is needed to increase serotonin levels to create an equilibrium." He went on to say that the leading antidepressants of the last 10 years, including Paxil and Prozac, have been selective serotonin re-uptake inhibitors (SSRIs), which help by blocking the re-uptake of serotonin that has been released into the synapse and ultimately increases the amount of serotonin available.

Explaining the serotonin connection further was Mr. Ramazanov. "Some people are born with low levels of serotonin and therefore are predisposed to become more easily stressed and eventually depressed," he said. "Just as frequently, serotonin levels can be significantly depleted by traumatic life experiences, including physical injury and mental breakdown. Decreased neurotransmission of serotonin has been proposed to play a key role in the etiology of depression. In other words, depression may well be primarily a consequence of chronic insufficiency of serotonin in the brain."

Serotonin is made in the body from the essential amino acid L-tryptophan. During this process, L-tryptophan is converted into 5-hydroxytryptophan (5-HTP), which is the metabolic precursor of serotonin. The theory is that by taking 5-HTP as a supplement this will increase the levels of serotonin in the brain.

Mr. Stanek said that 5-HTP is a more natural alternative to SSRIs, which are known for having adverse side affects. Linnea's 5-HTP, he said, is a 99.5% pure natural extract from the seeds of the Griffonia simplicifolia tree. "Because it is a serotonin precursor, 5-HTP will balance out the serotonin levels in the brain," he said. Positive effects of supplementing with 5-HTP include alleviating depression, enhancing focus and creating better self-awareness. However, Mr. Stanek said that it could take three to five weeks of supplementation before the body's blood levels adjust and the effects of the product are seen.

The compound is backed by years of research in Europe where it is a much more mature product, according to Mr. Stanek. Up until a few years ago when 5-HTP encountered some obstacles relating to negative results published in a research report about "Peak X," it was a very successful product, he said. "Over the past few years companies who manufacture 5-HTP have certified it as Peak X free, which has halted the issue," he offered. "It has regained its prominence as a product because it works, going back 30 years in Europe."

Another amino acid that has gained recognition for its relaxation properties is L-theanine, which is commonly found in green tea. NutriScience's Ms. Thibeau explained that L-theanine was first discovered in tea leaves in 1950 and was given food additive approval by the Japanese Ministry of Health and Welfare in 1964. "Tea leaves are a natural source of L-theanine, however, only one to two percent of the dry weight of tea leaves consists of L-theanine," she said. "It is a very time consuming and expensive process to extract L-theanine from tea leaves and impossible to yield 100% purity naturally."

Because of this, Taiyo Kagaku of Japan developed a patented enzymatic technology to synthesize 100% pure L-theanine, yielding Suntheanine®, which is sold through NutriScience Innovations. According to the company, Suntheanine is structurally identical to the L-theanine compound found naturally in green tea.

Going into further detail about the product was Ms. Thibeau. "Suntheanine is used to promote relaxation, reduce stress, ease nervousness and reduce restlessness due to common everyday overwork and fatigue," she said. "It is absorbed through the brush-border membrane in the large intestine and transported directly to the brain where it stimulates the generation of alpha brain waves, which signify an awake, alert and relaxed state without causing drowsiness or impairing motor skills."

In terms of science, Suntheanine is backed by more than 60 studies and clinical trials and is protected by more than 40 internationally recognized patents for both use and manufacturing. According to Ms. Thibeau dosages of Suntheanine are effective at 50-100 mg and its effects are exhibited within 30 to 40 minutes of consumption.


Herbal Compounds
There are several phytomedicines with a long history of traditional use and very promising anti-stress and mood-enhancing properties that have been introduced in the past, such as St. John's Wort, ginkgo biloba, magnolia bark extract and Rhodiola rosea root extract, according to National BioScience's Mr. Ramazanov. However, he said that due to recent negative publicity, the demand and consumer trust toward some effective phytomedicines has declined. "Yet, it is possible consumer confidence of mood-enhancing phytomedicines declined due to the lack of adequate preparation of herbal extracts, their standardization and their adulteration," he commented. "Despite this handicap many worthwhile products have prevailed and become widely accepted, benefiting the general public."

Rhodiola rosea is one of the phytomedicines that has been clinically researched in relation to chronic stress and mood disorders. Discussing its background, Mr. Ramazanov said that while it is relatively new to the American dietary supplement market, it has a long history of use in Russia, where it originates. It is also known as "Golden root," and has been used for centuries to cope with the cold Siberian climate and stressful life.

"Forty years of Soviet/Russian science suggests that Rhodiola rosea has enormous potential for improving health conditions in the modern world," said Mr. Ramazanov. "Research involving dozens of investigators and scores of experiments signify that Rhodiola rosea deserves to be taken seriously by health experts in the U.S. for its potential in alleviating the adverse health impact of chronic stress."

Mr. Ramzanov went into further detail about Rhodiola rosea's effect on the human system. "The systematic study of the pharmacological effects of Rhodiola rosea, begun in 1965, found that the root extract had a stimulating effect," he said. "It increased the bioelectrical activity of the brain, presumably by direct effects on the brainstem ascending and descending reticular formation. Rhodiola rosea stimulated norepinephrine, dopamine, serotonin, nicotinic cholinergic effects in the central nervous system and enhanced the effects of these neurotransmitters on the brain by increasing the permeability of the blood brain barrier to precursors of dopamine and serotonin."

According to Mr. Ramazanov, 75 mg to 150 mg twice daily or 150 mg to 300 mg per day is the optimal dose range of Rhodiola rosea standardized to 3% rosavins. "The time required to begin to feel the effects of the herb depends on an individual's genetics, mental and physical condition, environment, behavior and lifestyle," he explained. "Some people will feel its effects in just a few days and others will feel its effects in two to three weeks. Clinical studies show that most of those who benefit from Rhodiola rosea extract feel the effects within a maximum of 30-40 days. If a person does not feel some benefit within 40 days it makes sense for them to discontinue use as it is probably not suitable for them."

Another herb that has been gaining attention for alleviating stress and anxiety is Magnolia officinalis, which is the bark from the stem, root or branch of the magnolia tree. According to Brien Quirk, technical director, Draco Natural Products, San Jose, CA, it has a long history of use in Traditional Chinese Medicine (TCM), where it is known as Hou Po, and has primarily been used throughout the centuries to help treat digestive problems, asthma, cough and diarrhea. However, Mr. Quirk said that modern pharmacological research has focused on Magnolia officinalis for its sedative, tranquilizing and muscle relaxant properties as possible safer alternatives to conventional drugs.

"The studies on magnolia alone seem to indicate that compounds known as biphenols, including honokiol and magnolol, which are the main active constituents, bind to and activate GABA receptors in the brain," he explained. "GABA, or gama aminobutyric acid, is a neurotransmitter that inhibits brain activity so it has the ability to reduce anxiety and nervousness. There is excitement in pharmaceutical research about this compound because it doesn't cause motor impairment, loss of coordination, physical dependency or memory loss like the typical tranquilizing drugs Valium, Xanax and Ativan.

To date the most popular use of Magnolia is in Relora™, which is a patented combination of Magnolia officinalis and Phellodendron amurense manufactured by Next Pharmaceuticals, Irvine, CA.

An Ayuverdic herbal extract for mood health that has also been receiving attention lately is bacopa (Bacopa monniera), a natural mood-booster, which promotes healthy mental functions. It has been used in India for over 3000 years to help memory enhancement, epilepsy and insomnia and is also used as a mild sedative.

According to Ray Sahelian, M.D., in his book, Mind Boosters, the herb commonly grows in marshy areas throughout India. "Studies show that bacopa has antioxidant properties, protects mental function in those with epilepsy who take the drug phenytion and improves learning skills," he explained. "Two saponins, designated as bacopaside I and II, have been isolated from Bacopa monniera as its active components. Recent human studies have shown that bacopa improves communication between nerve cells in the brain."

Ayush Herbs' Mr. Sodhi said that bacopa extract has modulated the superoxide dismutase (SOD) and cytochrome 450 activity in animal brains, thereby preparing the brain for adverse conditions. "In humans, bacopa extract consumed in the dose of 300 mg per day has shown to improve mental function," he said.


Stress-Relieving Peptides
Ingredia Dairy Ingredients, Arras Cedex, France, launched PRODIET F 200, a spray dried milk protein hydrolysate with relaxing properties a few years ago. The ingredient is the result of more than 10 years of research and development in collaboration with a team from the University of Nancy. Ingredia discovered a natural peptide from milk within a protein hydrolysate with relaxing properties.

The efficacy of PRODIET F 200 toward stress has been proven in four clinical studies on a total of 130 volunteers, according to the company. Ingested for a period of 30 days, test results showed that PRODIET F 200 significantly reduced the mean blood pressure (MBP) change during the exposure to provoked stress (MBP variation is a marker of stress reactivity). In pre-clinical studies on rats, PRODIET F 200 did not induce any sedation, habituation, addiction, memory loss or any impairment of learning capacities, even at a high dose, Further, no side effects were observed during the different clinical studies. The company said it is also resistant to numerous industrial processes and its efficacy is stable over the course of time. PRODIET F 200 can be blended into chocolate, milky drinks and fruit juice type food products or marketed in supplement form.

Also involved in stress-relieving peptides is French homeopathy specialist Dolisos, Toulouse, France, who has launched a milk protein-based supplement designed to treat stress into the U.K. market. The new product, Seriane, contains a molecule produced from casein decapeptide derived from hydrolyzed milk proteins. It is the first Dolisos product available in the U.K. According to the company, studies have indicated that the peptide may help reduce levels of stress by producing a soothing effect. In addition, the company said Seriane is not addictive and does not produce any or other side effects such as weight gain.