Natural Foods Merchandiser

Depression-lifting supplements that work

Depression is big business. In any given year, an estimated 19 million people look for ways to ease sadness, anxiety and feelings of hopelessness associated with depression—a number that has made some pharmaceutical companies quite rich. But today, natural treatments for depression are giving drugs a run for their money. Thanks to loads of anecdotal evidence, as well as strong scientific evidence from clinical studies showing safety and efficacy, more people are discovering that herbs, vitamins and other supplements can be powerful enough to lift symptoms of depression without the unwanted side effects that often accompany drugs.

Although one of the strongest appeals of these natural approaches is that they can be used without a prescription, it is important to remind your customers to seek the guidance of a physician or other health care provider when beginning any treatment program. Additionally, because there are many types of mood disorders, professional help is essential to determine the nature and severity of the condition. While mild to moderate depression often responds well to natural remedies, more serious forms of mental illness—including severe depression and bipolar disorder—require the expertise of a qualified health care provider. The following natural remedies have a good track record and solid science to support their use in treating mild to moderate forms of depression.

St. John's wort
St. John's wort (Hypericum perforatum) is by far the most popular dietary supplement for depression. Because it produces effects similar to those of selective serotonin reuptake inhibitor drugs, such as Prozac, researchers believe the herb slows the rate at which brain cells use the neurotransmitter serotonin. Higher levels of available serotonin correlate to elevation in mood.

Beginning in the 1980s, a number of small studies suggested the herb was as effective for mild to moderate depression as tricyclic antidepressants, an older class of medications.1,2 Then, in 1996, the British Medical Journal published a meta-analysis of 23 randomized clinical trials conducted to investigate the effectiveness of St. John's wort's extract (standardized to 0.3 percent hypericin) in relieving depression; the trials involved a total of 1,757 people.3 The meta-analysis looked at trials that pitted St. John's wort against a placebo, as well as studies that compared the herb to standard SSRIs, such as Prozac. The meta-analysis concluded that individuals with mild to moderate depression fared better with St. John's wort (63.9 percent of patients improved) than with conventional SSRIs (58.5 percent).

Since then, several additional well-designed clinical trials have compared St. John's wort to leading antidepressants. For example, in a randomized, double-blind study published in 2000, German physicians treated 240 patients with mild to moderate depression with either 500 mg daily of St. John's wort extract or Prozac for six weeks.4 According to the Hamilton Depression Scale (a standard test used to assess depression), symptoms declined by about 12 percent in both groups. However, when using the Clinical Global Impression Scale, another test for depression, St. John's wort proved significantly more effective than Prozac.

Another double-blind, randomized study compared St. John's wort with the SSRI drug Zoloft. Thirty participants were given 500 mg to 600 mg of St. John's wort or Zoloft daily for seven weeks.5 Some improvement was seen in the St. John's wort group within two weeks, and after six weeks, symptoms of depression were reduced by an average of 47 percent in the St. John's wort group and by 40 percent among those taking Zoloft.

However, a widely publicized 2001 study cast a shadow over the promise of St. John's wort.6 Many believe the study was a charade with quite a few shortcomings. It examined the effects of St. John's wort in severe depression, not in the mild to moderate type for which it is typically recommended. Critics pointed out that no active pharmaceutical drug was used as a reference against which to compare St. John's wort and placebo, and the placebo response rates were unusually low for a depression study.7 The study was funded by Pfizer Inc., the manufacturer of the widely prescribed Zoloft. What's more, when scrutinized closely, the study results revealed that St. John's wort actually did benefit some severely depressed patients..6

St. John's wort safety
Today, most St. John's wort products are standardized to contain 3 percent to 5 percent hyperforin; most earlier studies utilized St. John's wort extract standardized to 0.3 percent hypericin. The process of standardization guarantees that a specified amount of an ingredient (presumably the active ingredient) is present in the herbal extract. Although there has been debate over the years as to exactly which constituents in St. John's wort are responsible for its activity, the Physician's Desk Reference for Herbal Medicine currently states that hyperforin—not hypericin—is likely the primary active ingredient for treating depression,8 but conclusive evidence is lacking. In addition, it is possible that other biologically active constituents of St. John's wort, such as flavonoids and tannins, also may play a role.9

In one well-controlled study involving 147 people with mild to moderate depression, subjects took either placebo, St. John's wort extract standardized to 0.5 percent hyperforin, or St. John's wort extract standardized to 5 percent hyperforin.10 Only the patients who received the 5 percent hyperforin extract showed significant improvement, leading the investigators to conclude that the effect of St. John's wort in depression depends on hyperforin.

In general, St. John's wort has been shown to produce very few side effects; these include mild gastrointestinal disturbances and photosensitivity (an allergic skin reaction that can occur upon exposure to sunlight) in some people. Some studies have indicated that the herb may interact with certain medications, including digoxin (used to treat congestive heart failure),11 theophylline (an asthma medication)12 and the HIV drug indinivir.13 Thus it is essential that those taking pharmaceutical medications check with a qualified health care practitioner before taking St. John's wort.

A recent study suggests that a hyperforin-free St. John's wort extract may pose fewer risks of drug interactions,14 but it is not known whether hyperforin-free extracts will deliver the same therapeutic benefits as extracts that contain hyperforin. In a randomized, placebo-controlled study of 96 healthy volunteers, a seven-day loading phase of digoxin was followed by 14 days of either a placebo or one of 10 different St. John's wort products that varied in dose and formulation. The investigators measured digoxin blood levels before adding St. John's wort and again on day 14 of the study. Results showed that the higher the dose of hyperforin, the more dramatic the interaction with digoxin. Placebo and hyperforin-free extract caused no significant interaction with digoxin, suggesting that hyperforin-free St. John's wort might be a safer option for those taking additional medications.14 But again, whether hyperforin-free St. John's wort extracts will deliver adequate mood-lifting effects remains to be determined.

Although it may sound synthetic, S-adenosyl-L-methionine is a naturally occurring compound involved in many biochemical processes. Supplemental SAM-e is known to ease the pain and stiffness caused by osteoarthritis15,16 and has been shown to support liver function.17 In addition, a good deal of research has focused on its ability to affect mood. SAM-e appears to relieve depression by enabling the brain to manufacture neurotransmitters such as dopamine, serotonin and norepinephrine.

A research review published in the American Journal of Clinical Nutrition in 2002 concluded that SAM-e relieves depression significantly more effectively than tricyclic antidepressants.18 Other studies have shown that in addition to working as well as antidepressant drugs, SAM-e has fewer side effects and is better tolerated. For example, in a double-blind study of people with a diagnosis of a major depressive episode, participants received either 400 mg per day of SAM-e (given intramuscularly) or 150 mg per day of oral imipramine, a tricyclic antidepressant. A total of 146 patients received SAM-e, and 147 received IMI for a period of four weeks. According to results, SAM-e was comparable to IMI in terms of antidepressive efficacy, but was significantly better tolerated.19 A number of other double-blind studies have also shown oral SAM-e can ease depression symptoms.20

Omega-3 fatty acids
Considering the brain is 60 percent fat, it is no wonder it needs adequate amounts of omega-3 fatty acids to function properly. In fact, recent clinical studies have shown a strong connection between low levels of omega-3 fatty acids and depression.

Plant sources of omega-3 fatty acids, such as flax, walnuts and hemp, contain the parent omega-3, alpha-linolenic acid, which can be converted into eicosapentaenoic acid and docosahexaenoic acid in the body. However, the conversion process is not efficient, meaning that consuming EPA and DHA directly from animal sources raises levels more quickly in the body, probably leading to better results. Cold-water fish, such as sardines, salmon and mackerel, as well as algae and fish oil supplements, are direct sources of EPA and DHA. Vegetarian DHA supplements are also available.

According to one study, the lower one's level of EPA, the more severe the clinical depression.21 What's more, people diagnosed with depression have been shown to have up to 35 percent less DHA in fat storage cells than healthy individuals.22 In one double-blind study of 70 patients with persistent depression, supplementation with 1 g, 2 g or 4 g of EPA per day for 12 weeks was significantly more effective than a placebo in relieving symptoms of depression.23

A recent study published in the British Journal of Psychiatry tested the efficacy of EPA supplementation in the treatment of bipolar depression, a much more severe mood disorder.24 In the 12-week, double-blind study, 26 participants with the condition were randomly assigned to take placebo, 24 to take 1 g of EPA and 25 to take 2 g of EPA daily. People who took either dose of EPA had a significantly greater improvement in symptoms of depression than those who took placebo, although there was no apparent benefit to the higher 2 g dose.

Chromium picolinate
While chromium picolinate has not been proven to lift mild to moderate depression on its own, recent studies have shown the mineral can have an impact in the treatment of a specific type of depression known as atypical depression. Despite its name, atypical depression is quite common and is generally associated with symptoms such as weight gain, carbohydrate cravings and appetite increase.

In a small, placebo-controlled, double-blind study published in Biological Psychiatry, 15 individuals with atypical major depression were given either 600 mg chromium picolinate or a placebo for eight weeks.25 Results showed 70 percent of chromium-treated participants experienced improvement in symptoms of depression; none of those taking placebo experienced improvement (an extremely low placebo response rate). Chromium was well-tolerated.

Another study demonstrated that chromium might have the ability to assist in insulin regulation, helping to stabilize blood sugar and curb cravings that often accompany depression. In a recent double-blind, placebo-controlled study published in the Journal of Psychiatric Practice, 113 people with atypical depression were randomly assigned to receive 600 mg a day of chromium picolinate for eight weeks, or a placebo.26 Although the chromium did not significantly improve overall symptoms of depression in all participants, it did cut carbohydrate cravings in those who had them. In addition, chromium seemed to improve depression symptoms in those individuals with such cravings.

The discovery of chromium's ability to ease mood-related cravings is likely a foreshadowing of what is yet to come in the realm of natural treatments for mood disorders. For example, a recent double-blind, randomized study showed an extract of Echium amoenum (a plant in the borage family) was significantly better than placebo in relieving symptoms of mild to moderate depression.27 In other words, we can likely expect to see an even larger array of powerful mood-lifting supplements on store shelves soon.

Linda Knittel is a Portland, Ore.-based freelance writer. She is the author of User's Guide to Natural Remedies for Depression (Basic Health Publications, 2003).

What to recommend

Because individual nutrient needs and restrictions vary, remind your customers to seek the guidance of a trained health care practitioner before starting any treatment program. The dosages below are general guidelines that have proven effective and safe in clinical studies.

St. John's wort: Clinical studies have used a daily dose of 900 mg of St. John's wort extract standardized to 3 percent hyperforin. This herb may interact with some medications, so advise your customers to be sure to consult a physician if they are taking any medication, pregnant, nursing or scheduled for surgery. Occasionally St. John's wort will cause photosensitivity (an allergic skin reaction to sunlight).

SAM-e: Clinical studies have used a daily dose of 400 mg of SAM-e. Take on an empty stomach. People who are on any type of medication or are pregnant, nursing or scheduled for surgery should consult a physician.

Omega-3 fatty acids: A daily dose of 300 g of EPA plus 200 g of DHA has been used in clinical trials. That may require 10 g of fish oil, because most fish oil contains only 18 percent EPA and 12 percent DHA. Concentrated products have succeeded in squeezing this amount into one capsule. Consumers should consult a physician if they are taking any medication, scheduled for surgery, pregnant or nursing. Look for products that have been tested for heavy-metal content.

Chromium picolinate: A daily dose of 600 mg has been used in clinical studies. Chromium picolinate has not been shown to cause toxicity when taken at recommended levels. Because chromium can influence insulin levels in the body, anyone with blood sugar issues should consult a health care practitioner before taking this mineral.

1. Vorbach EU, et al. Efficacy and tolerability of St. John?s wort extract LI 160 versus imipramine in patients with severe depressive episodes according to ICD-10. Pharmacopsychiatry 1997;30(suppl):81?5.
2. Wheatley D. LI 160, an extract of St. John?s wort, versus amitriptyline in mildly to moderately depressed outpatients?a controlled 6-week trial. Pharmacopsychiatry 1997;30(suppl):70?80.
3. Linde K, et al. St. John?s wort for depression?an overview and meta-analysis of randomized clinical trials. BMJ 1996;313(7052):253?8.
4. Schrader E. Equivalence of St John?s wort extract (Ze 117) and fluoxetine: a randomized, controlled study in mild?moderate depression. Int Clin Psychopharmacol 2000;15:61?8.
5. Brenner R, et al. Comparison of an extract of hypericum (LI 160) and sertraline in the treatment of depression: a double-blind, randomized pilot study. Clin Ther 2000;22:411?9.
6. Shelton RC, et al. Effectiveness of St John?s wort in major depression. A randomized controlled trial. JAMA 2001;285:1978?86.
7. American Botanical Council. Questions Raised About Latest St. John?s Wort Study in JAMA.
8. Physician?s Desk Reference for Herbal Medicines (2nd ed.). New Jersey: Medical Economics Company, Inc. 2000;488?9.
9. Nahrstedt A and Butterweck V. Biologically active and other chemical constituents of the herb of Hypericum perforatum L. Pharmacopsychiatry 1997;30(Suppl 2),129?34.
10. Laakmann G, et al. St. John?s wort in mild to moderate depression: the relevance of hyperforin for the clinical efficacy. Pharmacopsychiatry 1998;31:s54?s59.
11. Johne A, et al. Pharmacokinetic interaction of digoxin with an herbal extract from St. John?s wort. Clin Pharmacol Ther 1999;66:338?45.
12. Nebel A, et al. Potential metabolic interaction between St. John?s wort and theophylline. Ann Pharmacother 1999;33:502.
13. Piscitelli SC, et al. Indinavir concentrations and St. John?s wort. Lancet 2000;355:547?8.
14. Mueller SC, et al. Effect of St John?s wort dose and preparations on the pharmacokinetics of digoxin. Clin Pharmacol Ther 2004 Jun;75(6):546?7.
15. Vetter G. Double-blind comparative clinical trial with S-adensylmethionine and indomethacin in the treatment of osteoarthritis. Am J Med 1987;83(suppl 5A):78?80.
16. Maccagno A. Double-blind controlled clinical trial or oral S-adenosylmethionine versus piroxicam in the knee osteoarthritis. Am J Med 1987;83(suppl 5A):72?7.
17. Angelico M, et al. Oral S-adenosyl-L-methionine (SAMe) administration enhances bile salt conjugation with taurine in patients with liver cirrhosis. Scand J Clin Lab Invest 1994;54:459?64.
18. Mischoulon D and Fava M. Role of S-adenosyl-L-methionine in the treatment of depression: a review of the evidence. Am J Clin Nutr. 2002;76(5):1158S?61S.
19. Pancheri P, et al. A double-blind, randomized parallel-group, efficacy and safety study of intramuscular S-adenosyl-L-methionine 1,4-butanedisulphonate versus imipramine in patients with major depressive disorder. Int J Neurospycholpharmacol 2002;5(4):287?94.
20. Bressa GM. S-adenosyl-l-methionine (SAMe) as antidepressant: Meta-analysis of clinical studies. Acta Neurol Scand 1994;154(suppl):7?14.
21. Adams PB, Lawson S, et al. Arachidonic acid to eicosapentanoic acid ratio in blood correlates positively with clinical symptoms of depression. Lipids 1996; 31: S157?S161.
22. Mamalakis G, Tornaritis M, et al. Depression and adipose essential polyunsaturated fatty acids. Prostaglandins Leukot Essent Fatty Acids 2002; 67: 311?18.
23. Peet M and Horrobin DF. A dose-ranging study of the effects of ethyl-eicosapentaenoate in patients with ongoing depression despite apparently adequate treatment with standard drugs. Arch Gen Psychiatry. 2002;59(10):913?9.
24. Frangou S, et al. Efficacy of ethyl-eicosapentaenoic acid in bipolar depression: randomised double-blind placebo-controlled study. Br J Psychiatry 2006 Jan;188:46?50.
25. Davidson JR, et al. Effectiveness of chromium in atypical depression: a placebo-controlled trial. Biol Psychiatry 2003;53(3):261?4.
26. Docherty JP, et al. A double-blind, placebo-controlled, exploratory trial of chromium picolinate in atypical depression: effect on carbohydrate craving. J Psychiatr Pract 2005;11(5):302?14.
27. Sayyah M and Kamalinejad M. A preliminary randomized double blind clinical trial on the efficacy of aqueous extract of Echium amoenum in the treatment of mild to moderate major depression. Prog Neuropsychopharmacol Biol Psychiatry 2006;30(1):166?9. Epub 2005 Nov 23.

Natural Foods Merchandiser volume XXVII/number 5/p. 38, 40

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