The Encyclopedia of Natural Medicine, 3rd Ed.

Anxiety

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• Nervousness, anxiety, or inappropriate sense of fear

• Shortness of breath, heart palpitations, and tingling sensations in the extremities

More than 20 million Americans suffer from anxiety, an unpleasant emotional state that can range from mild unease to intense fear. Anxiety differs from fear in that while fear is a rational response to a real danger, anxiety usually lacks a clear or realistic cause. Though some anxiety is normal and even healthy, higher levels of anxiety not only are uncomfortable but also can lead to significant problems.

Anxiety is often accompanied by a variety of symptoms. The most common symptoms relate to the chest, such as heart palpitations (awareness of a more forceful or faster heart beat), throbbing or stabbing pains, a feeling of tightness or inability to take in enough air, and a tendency to sigh or hyperventilate. Tension in the muscles of the back and neck often leads to headaches, back pains, and muscle spasms. Other symptoms can include excessive sweating, dryness of the mouth, dizziness, digestive disturbances, and the constant need to urinate or defecate.

Anxious individuals usually have a constant feeling that something bad is going to happen. They may fear that they have a chronic or dangerous illness—a belief that is reinforced by the symptoms of anxiety. Inability to relax may lead to difficulty in getting to sleep and constant waking in the night.

Panic Attacks

Severe anxiety will often produce what are known as “panic attacks”—intense feelings of fear. Panic attacks may occur independently of anxiety but are most often associated with generalized anxiety or agoraphobia. Agoraphobia is an intense fear of being in public places. As a result, most people with agoraphobia become housebound.

Panic attacks are very common; about 15% of the U.S. population will experience a panic attack in their lifetime. Among adults ages 25 to 54, about 1.5 to 3% experience frequent panic attacks.

Causes

Clinical anxiety, including panic attacks, can be produced by psychological problems as well as by biochemical factors such as caffeine, certain other drugs, and the infusion of lactate into the blood. The fact that these compounds can produce anxiety and panic attacks can be put to good use in understanding the underlying biochemical features of anxiety.

Perhaps the most significant biochemical disturbance noted in people with anxiety and panic attacks is an elevated blood lactic acid level and an increased ratio of lactic acid to pyruvic acid. Lactate (the soluble form of lactic acid) is the final product in the breakdown of blood sugar (glucose) when there is a lack of oxygen.

To illustrate how lactic acid is produced, let’s take the classic example of the exercising muscle. Muscles prefer to use fat as their energy source, but when you exercise vigorously there isn’t enough oxygen, so the muscle must burn glucose. Without oxygen, there is a buildup of lactic acid within the muscle; this is what causes muscle fatigue and soreness after exercise. Let’s look more closely at this process.

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Lactic Acid Conversion to Pyruvic Acid or Glucose

The first few steps of normal glucose breakdown can occur without oxygen, until pyruvic acid is produced. The next steps require oxygen and end in the complete breakdown of pyruvic acid to carbon dioxide and water. But what happens if there is not enough oxygen? Because the exercising muscle needs energy, the muscle cells continue to convert glucose to pyruvic acid in a process referred to as anaerobic metabolism. The pyruvic acid is then converted into a temporary waste product, lactic acid. With good circulation, the lactic acid is removed from the muscle and transported to the liver, where it can be turned back into pyruvic acid or even glucose if needed.

All of this biochemistry plays a role in anxiety, because individuals with anxiety have elevated blood levels of lactate and a higher ratio of lactic acid to pyruvic acid when compared with normal controls. Furthermore, if people who get panic attacks are injected with lactate, severe panic attacks are produced. In normal individuals nothing happens. So it appears that individuals with anxiety may be sensitive to lactate. In other words, lactate may be causing their anxiety. Reducing the level of lactate is a critical goal in the treatment of anxiety and panic attacks.

Therapeutic Considerations

The natural approach to anxiety builds upon the recommendations given for stress in the chapter “Stress Management.” After all, anxiety is usually a symptom of severe stress. If you suffer from mild anxiety, follow all of the recommendations given in that chapter for diet, exercise, nutritional supplementation, calming the mind and body, and taking an adrenal adaptogen. If you suffer from moderate to severe anxiety, follow all of the recommendations in that chapter as well as those discussed below; substitute kava for the adrenal adaptogen.

Lactate Levels

As pointed out previously, increased lactic acid levels may be an underlying factor in panic attacks and anxiety. The goal is to prevent the conversion of pyruvic acid to lactic acid and to improve the conversion of lactic acid back to pyruvic acid. Nutrition appears to play a key role in achieving this goal. There are at least six nutritional factors that may be responsible for elevated lactate levels or ratios of lactic acid to pyruvic acid:1

1. Alcohol

2. Caffeine

3. Sugar

4. Deficiency of the B vitamins niacin, pyridoxine, and thiamine

5. Deficiency of calcium or magnesium

6. Food allergens

By avoiding alcohol, caffeine, sugar, and food allergens, people with anxiety can go a long way toward relieving their symptoms. Simply eliminating coffee can result in complete relief from symptoms. This recommendation may seem too simple to be valid, but substantial clinical evidence indicates that in many cases it is all that is necessary. For example, one study dealt with four men and two women who had generalized anxiety or panic disorder. Their caffeine consumption ranged from 11/2 to 31/2 cups of coffee per day. Avoiding caffeine for one week brought about significant relief of symptoms.2 The degree of improvement was so noticeable that all patients volunteered to continue abstaining from caffeine. Previously, these patients had been only minimally helped by drug therapy. Follow-up exams 6 to 18 months afterward indicated that five out of the six patients were completely without symptoms; the sixth patient became asymptomatic with a very low dose of Valium.

By following the guidelines in the chapter “A Health-Promoting Diet,” as well as the recommendations for nutritional supplementation given in the chapter “Supplementary Measures,” you will provide your body with the kind of nutritional support it needs to counteract the biochemical derangements found in patients with anxiety and panic attacks.

Nutritional Supplements

Omega-3 Fatty Acids

Anxiety and depression appear to be linked to lower levels of omega-3 fatty acids.3 The mechanism appears to be that both depression and anxiety can enhance the production of pro-inflammatory compounds known as cytokines. A high intake of omega-6 fatty acids (found in corn-fed animal products, dairy products, and common vegetable oils such as corn, soy, safflower, and sunflower) and a low intake of omega-3 fatty acids (found in fish, fish oils, and flaxseed oil) can lead to an amplification in the production of these cytokines. Cytokines not only promote inflammation but also appear to affect the way we feel. So increasing the intake of omega-3 fatty acids and lowering the intake of omega-6 fatty acids may help to reduce anxiety and depression. The positive results seen with fish oil supplements in clinical depression are well documented. In regard to anxiety, one clinical study showed that fish oil supplementation decreased feelings of anger and anxiety in substance abusers.4 In a detailed study involving medical students, 2.5 g long-chain omega-3 fatty acids (2,085 mg EPA and 348 mg DHA) from fish oils per day produced a 14% decrease in cytokine production and a 20% reduction in anxiety symptoms.5

Flaxseed oil, a source of the short-chain omega-3 fatty acid alpha-linolenic acid, has also shown antianxiety effects. In one study, three out of four patients with a history of agoraphobia for 10 or more years improved within two to three months after taking flaxseed oil at a dosage of 2 to 6 tbsp per day, in divided doses depending upon response.6 All patients had signs of essential fatty acid deficiency, such as dry skin, dandruff, brittle fingernails that grow slowly, and nerve disorders.

Kava

The area of Oceania—the island communities of the Pacific, including Micronesia, Melanesia, and Polynesia—is one of the few geographic areas in the world that did not have alcoholic beverages before European contact in the 18th century. However, these islanders did possess a magical drink that was used in ceremonies and celebrations because of its calming effect and ability to promote sociability. The drink, called kava, is still used today in this region, where the people are often referred to as the happiest and friendliest in the world. Preparations of kava root (Piper methysticum) gained popularity in Europe and the United States up until 2001, when safety concerns (discussed below) derailed their popularity.

Several clinical trials utilized a special kava extract standardized to contain 70% kavalactones. However, this high percentage of kavalactones may be sacrificing some of the other constituents that may contribute to the pharmacology of kava. Therefore, preparations around 30% may prove to be the most effective. More important than the actual percentage of kavalactones is the total dosage of the kavalactones and the assurance that the full range of kavalactones is present.

In one of the first double-blind studies, a 70% kavalactone extract was shown to exhibit significant therapeutic benefit in patients suffering from anxiety.7 Twenty-nine patients were assigned to receive 100 mg kava extract three times per day, while another 29 patients received a placebo. Therapeutic effectiveness was evaluated using several standard psychological assessments, including the Hamilton Anxiety Scale. The results of this four-week study indicated that individuals who took kava extract had a statistically significant reduction in symptoms of anxiety, including feelings of nervousness and somatic complaints such as heart palpitations, chest pains, headache, dizziness, and feelings of gastric irritation. No side effects were reported with the kava extract.

Studies have also compared the effects of a kava extract with antianxiety drugs such as buspirone and opipramol. In one double-blind study, 129 patients with generalized anxiety disorder were given either 400 mg kava (30% kavalactones), 10 mg buspirone, or 100 mg opipramol per day for eight weeks. Detailed analysis showed that no significant differences could be observed in terms of efficacy and safety. About 75% of patients were classified as responders (at least a 50% reduction of the anxiety score) in each treatment group, and about 60% achieved full remission.8

Kava has also been shown to be particularly effective in relieving anxiety in perimenopausal and postmenopausal women.911 In one double-blind study, two groups of 20 women with menopause-related symptoms were treated with 70% kavalactone extract (100 mg three times per day) or a placebo.11 The measured variable was once again the Hamilton Anxiety Scale. The group receiving the kava extract demonstrated significant improvement at the end of the very first week of treatment. Scores continued to improve over the course of the eight-week study. In addition to symptoms of stress and anxiety, a number of other symptoms also improved. Most notably there was an overall improvement in subjective well-being, mood, and general symptoms of menopause, including hot flashes. As with previous studies, no side effects were noted.

Additional studies have shown that unlike benzodiazepines (Valium-like drugs), alcohol, and other drugs, kava extract is not associated with depressed mental function or impairment in driving or the operation of heavy equipment.12,13 In one of these studies, 12 healthy volunteers were tested in a double-blind crossover manner to assess the effects of oxazepam, 70% kavalactone extract (200 mg three times per day for five days), and a placebo.13The subjects’ task was to identify within a list of visually presented words those that were shown for the first time and those that were being repeated. Like other benzodiazepines, oxazepam inhibited the recognition of both new and old words. In contrast, kava allowed a slightly greater recognition rate and a larger difference between old and new words. The results of this study once again demonstrate the unusual effects of kava. In this case, it relieves anxiety, but unlike standard antianxiety drugs, kava actually improves mental function and, at the recommended levels, does not promote sedation.

In 2009, the first documented human clinical trial assessing the antianxiety and antidepressant efficacy of a water-based extract of kava was published.14 The Kava Anxiety Depression Spectrum Study was a three-week placebo-controlled, double-blind crossover trial that recruited 60 adult participants with one month or more of elevated generalized anxiety. The kava preparation produced significant antianxiety and antidepressant activity and raised no liver toxicity or safety concerns at the dose and duration studied. Specifically, kava reduced participants’ Hamilton Anxiety Scale score in the first controlled phase by –9.9 vs. –0.8 for the placebo and in the second controlled phase by –10.3 vs. +3.3. Pooled analyses also revealed highly significant relative reductions in other anxiety and depression scale scores.

The dosage of kava preparations is based on their level of kavalactones. As a result of clinical studies, the recommendation for anxiety-relieving effects is 45 to 70 mg kavalactones three times per day. For sedative effects, the same daily quantity (135 to 210 mg) can be taken as a single dose one hour before retiring.

To put the therapeutic dosage in perspective, it is important to point out that a standard bowl of traditionally prepared kava drink contains approximately 250 mg kavalactones, and several bowls may be consumed at one sitting.

Kava can have significant side effects. In November 2001, German health authorities announced that 24 cases of liver disease (including hepatitis, liver failure, and cirrhosis) associated with the use of kava had been reported; of the affected individuals, one died and three required a liver transplant. As a result, in December 2001 the U.S. Food and Drug Administration began advising consumers of the potential risk of severe liver injury associated with the use of kava-containing dietary supplements. Kava was subsequently withdrawn form the market in the European Union, the United Kingdom, and Canada. In 2007, Germany reevaluated the data and allowed kava back on the market.

In the initial report the true nature of kava-induced liver damage was clouded by the fact that in 18 of these cases, conventional prescription or over-the-counter pharmaceutical drugs with known or potential liver toxicity were also being used. Proponents of kava quickly argued that it was entirely possible that the use of kava by these individuals was a coincidence rather than the cause of the liver problem. As of 2007 of the approximately 100 cases of liver toxicity that had been reported worldwide, only in 14 cases was causality deemed to be “probable.”15 Two drug monitoring studies, including a total of 7,078 patients taking 120 to 150 mg kava extract per day, had not found a single case of kava-induced liver toxicity. Nonetheless, as of 2011, the liver toxicity of kava cannot be ruled out.

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QUICK REVIEW

• Perhaps the most significant biochemical disturbance noted in people with anxiety and panic attacks is an elevated blood lactate level.

• There are at least six nutritional factors that may be responsible for an elevated ratio of lactic acid to pyruvic acid:

  images Alcohol

  images Caffeine

  images Sugar

  images Deficiency of the B-vitamins niacin, pyridoxine, and thiamine

  images Deficiency of calcium or magnesium

  images Food allergens

• Kava extract has produced relief from anxiety comparable to that from drugs such as Valium, but it must be used with caution and is contraindicated for those with liver disease.

The existing data are complex, but it looks as if the major factor in any kava-induced liver toxicity was the use of non-root parts such as stems and leaves as well as stem peelings.16 It turns out that there wasn’t enough kava root to meet skyrocketing demand. Suppliers then knowingly or unknowingly bought the leaves and peelings of kava. Up until that development, the only parts of the kava plant that were traditionally used throughout its 3,000-year history were the roots, never the peelings or the leaves. According to a WHO report, German pharmaceutical industries preferred to buy kava stem peelings to extract kavalactones to make kava drugs; kava stem peelings were sold at almost one-tenth of the price of kava roots.17 In addition, dosage may also have been a factor in some of the cases of liver toxicity. A survey of 400 German medical practices showed that 78% of the kava prescriptions that were written prior to 2001 significantly exceeded the recommended intake.18 Nonetheless, there have been reports of hepatitis in patients using kava at dosages equal to or only slightly higher than recommended levels, indicating other factors beyond dosage.19 Flavokawain B, a chalcone from kava root, has been identified as a potent liver toxin.

Measures suggested to address the liver toxicity issue include (1) use of a noble kava cultivar that is at least five years old at time of harvest, (2) use of peeled and dried rhizomes and roots, (3) dosage recommendation of ≤250 mg kavalactones per day (for medicinal use), and (4) manufacturer quality control systems enforced by strict policing.16 Another important step may be determination of flavokawain B. It should be mentioned that while it has been suggested that traditional aqueous extracts should be used instead of alcoholic or acetonic extracts, the toxicity is linked to the kava plant itself, possibly with a low-quality plant or wrong plant part, rather than the method of extraction or solvent.20

At this time, kava is not recommended for use by anyone who has any liver problems or who is a regular consumer of alcohol. Use of kava for more than four weeks requires close monitoring of liver enzymes once every four to six weeks. Patients should be instructed to discontinue use of kava if symptoms of jaundice (e.g., dark urine, yellowing of the eyes) occur. Nonspecific symptoms of liver disease include nausea, vomiting, light-colored stools, unusual tiredness, weakness, stomach or abdominal pain, and loss of appetite. Kava is not recommended for use by pregnant or breastfeeding women.

Kava has the potential to interact with a wide range of medications and may also potentiate the effects of benzodiazepines, barbiturates, and prescription sedative drugs (sleeping pills).21 There is also evidence that kava interferes with dopamine or other drugs used in the treatment of Parkinson’s disease; therefore, until this issue is resolved, kava extract should not be used by patients with Parkinson’s disease.22

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TREATMENT SUMMARY

Effective treatment for anxiety must address psychological as well as physiological factors. In that regard, it is important to follow these recommendations:

• Reduce or eliminate the use of stimulants.

• Follow the dietary, lifestyle, and supplement recommendations in the chapter “Stress Management,” as well as those given below.

Note: If you are currently taking a sedative-hypnotic or antidepressant drug, you will need to work with a physician to get off the drug. Stopping the drug on your own can be dangerous; you absolutely must have proper medical supervision.

Diet

Follow the guidelines in the chapter “A Health-Promoting Diet.” It is especially important to:

• Eliminate or restrict caffeine

• Eliminate or restrict alcohol

• Eliminate refined carbohydrates

• Increase the potassium-to-sodium ratio of the diet

• Eat regular planned meals in a relaxed environment

• Control food allergies

Lifestyle

Follow the recommendations in the chapter “A Health-Promoting Lifestyle” and the chapter “Stress Management.” It is especially important to:

• Identify stressors

• Eliminate or reduce sources of stress

• Identify negative coping patterns and replace them with positive ones

• Perform a relaxation/breathing exercise for a minimum of five minutes twice a day

• Manage time effectively

• Enhance relationships through better communication

• Get regular exercise

Nutritional Supplements

• A high-potency multiple vitamin and mineral formula as described in the chapter “Supplementary Measures”

• Key individual nutrients:

  images Calcium: 1,000 mg per day

  images Magnesium: 350 to 500 mg per day.

  images Vitamin D3: 2,000 to 4,000 IU per day (ideally, measure blood levels and adjust dosage accordingly)

  images Vitamin B6: 25 to 50 mg per day

  images Folic acid: 800 mcg per day

  images Vitamin B12: 800 mcg per day

  images Vitamin K2 (MK-7): 100 mcg per day

• Fish oils: 1,000 to 3,000 mg EPA + DHA per day

• Flaxseed oil: 1 tbsp per day

• One of the following:

  images Grape seed extract (>95% procyanidolic oligomers): 100 to 300 mg per day

  images Pine bark extract (>95% procyanidolic oligomers): 100 to 300 mg per day

  images Or some other flavonoid-rich extract with a similar flavonoid content, “super greens formula,” or another plant-based antioxidant that can provide an oxygen radical absorption capacity (ORAC) of 3,000 to 6,000 units or more per day

Botanical Medicines

• One of the following:

  images Panax ginseng (Chinese or Korean ginseng):

High-quality crude ginseng root: 1.5 to 2 g one to three times per day

Fluid extract (containing a minimum of 10.5 mg/ml ginsenosides with an Rb1/Rg1 ratio of 2:1): 2 to 4 ml (1/2 to 1 tsp) one to three times per day

Solid (dry powdered) extract (standardized to contain 5% ginsenosides with an Rb1/Rg1 ratio of 2:1): 250 to 500 mg one to three times per day

  images Siberian ginseng (Eleutherococcus senticosus):

Dried root: 2 to 4 g one to three times per day

Fluid extract (1:1): 2 to 4 ml (1/2 to 1 tsp) or 2 to 4 g one to three times per day

Solid (dry powdered) extract (20:1, or standardized to contain more than 1% eleutheroside E): 100 to 200 mg or 2 to 4 g one to three times per day

  images Rhodiola rosea (Arctic root): For a dosage target of 3.6 to 7.2 mg rosavin, the daily dose would be 360 to 600 mg for an extract standardized for 1% rosavin, 180 to 300 mg for 2% rosavin, and 100 to 200 mg for 3.6% rosavin.

  images Withania somnifera (ashwagandha), equivalent to Sensoril: 125 to 250 mg per day22

  images Kava (Piper methysticum): dosage equivalent to 45 to 70 mg kavalactones three times per day