Depression, Diabetes, Obesity

Depression, Diabetes, Obesity – Alternative Therapies, part 1

Vincent Morelli

Natural supplements are widely used in the United States and, while claims of their therapeutic effects abound, medical research does not always support their effectiveness. St. John’s wort acts as a weak selective serotonin reuptake inhibitor with fewer side effects. S-Adenosylmethionine (SAMe) has enough of an antidepressant effect to warrant further research. More human studies are needed before garlic, bitter melon, soy and fenugreek supplements can be recommended for the management of diabetes, although chromium may be a promising treatment in some cases. Alpha lipoic acid is used in the treatment of diabetic neuropathy. The effects of ma huang/guarana combinations in obesity have not been well studied. These combinations may have potentially serious side effects but may also offer some benefit. The combination of hydroxycitric acid and garcinia has proved no more effective than placebo. (Am Fam Physician 2000;62:1051-60.)

Because the number of family physicians recommending nutritional supplements to treat a variety of diseases is increasing, an awareness of the medical and legislative issues surrounding these products is critical.

In 1994, a grassroots campaign led to congressional passage of the Dietary Supplement Health and Education Act. This legislation restricted the authority of the U.S. Food and Drug Administration (FDA) over any herb or supplement as long as the manufacturer makes no claim that the product is able to affect a “disease state.” Under this legislation, a supplement is presumed safe until the FDA receives “numerous reports” of adverse effects. (From 1993 to 1998, the FDA received 2,621 reports of adverse effects linked to supplements. These complaints included reports of 101 deaths.) Family physicians must be aware of this lack of scientific oversight and must be on the alert for any side effects, including effects that have not yet been documented.(1)

It is also important to note that under this legislation, no standardization of the manufacturing of herbs or supplements is required. Although the supplement industry is currently moving to police itself in this regard, physicians and patients must be informed that supplements often contain varying amounts of active ingredients.(1)

American Family Physician has previously published articles that focus on herbal products and their side effects, as well as herb/drug interactions.(2,3) For the most part, this article will focus on products not previously discussed in this journal. In this first part of a two-part article, we will highlight depression, diabetes and obesity, three conditions commonly encountered in the family physician’s office, and discuss the role that natural products can play in the treatment of these medical conditions. Tables 1, 2 and 3 summarize information about the natural products discussed.

Depression

The effectiveness and side effects of selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) are well documented. Relatively new potential additions to the armamentarium against depression include St. John’s wort and S-adenosylmethionine (SAMe).

ST. JOHN’S WORT

St. John’s wort (Hypericum perforatum) appears to act as a weak SSRI and may have an affinity for sigma receptors as well. Its clinical effectiveness may be attributable to a combination of mechanisms because each mechanism by itself is too weak to provide the overall effect.(4,5)

Studies have compared TCAs (i.e., imipramine [Tofranil], amitriptyline [Elavil]) with St. John’s wort in cases of mild to moderate depression and found no statistical differences between groups as evaluated by the Hamilton Depression Scale. One-third fewer side effects were noted in the subjects taking St. John’s wort, compared with the subjects taking amitriptyline.(6)

Initially, it was thought that this botanical supplement rarely, if ever, led to any drug interactions.(7) However, recent evidence(8,9) indicates interactions with digoxin, theophylline (decreased bioavailability), protease inhibitors (lowering the level of indinavir [Crixivan]), and drugs used to combat transplant rejection (increasing the metabolism of cyclosporine [Sandimmune]) via induction of cytochrome P450 enzymes. It also may cause seratonin syndrome if used with other antidepressants.

Results of 29 clinical trials(10,11) have demonstrated that St. John’s wort is more effective than placebo in the treatment of mild to moderate depression. As yet, there is insufficient evidence comparing the efficacy of St. John’s wort with conventional, modern antidepressants. We could find no studies that used St. John’s wort in combination with other modalities to treat severe depression or treatment-resistant depression, and it should not be used in these patients.

S-ADENOSYLMETHIONINE (SAME)

Another potential antidepressant is SAMe, which is a molecule found naturally in all human cells. It plays a role in the many methylation reactions of the body, including gene expression, cell membrane homeostasis, and hormone and neurotransmitter synthesis.

The rationale for the use of SAMe in depression stems from its role in the metabolism of serotonin, dopamine and melatonin. Oral and intravenous SAMe supplementation has been shown to significantly increase SAMe levels in cerebrospinal fluid, indicating SAMe’s crossover through the blood-brain barrier. This has been associated with increased levels of serotonin metabolites in cerebrospinal fluid. Some depressed patients may have low serotonin levels associated with low levels of SAMe.(12,13)

A 1994 meta-analysis(14) performed in Italy found SAMe more efficacious than placebo in the treatment of depression and equally as effective as TCAs, with a much lower incidence of side effects. In a double-blind trial conducted that same year,(15) 26 patients received SAMe or desipramine for four weeks. At the end of the study period, 62 percent of the patients taking SAMe had significant improvement in symptoms, while only 50 percent of the patients taking desipramine had significant improvement. The study did not extend beyond this short observational period, leaving unanswered questions about the long-term side effects of SAMe and whether the antidepressant effects of SAMe persist beyond four weeks. The study did not take into account the usual four- to eight-week time period needed for TCAs to become maximally effective. The investigators did note, however, that all patients who showed a 50 percent decrease in their Hamilton Depression Scale scoring also showed a significant increase in plasma SAMe concentration.(15)

In 1995, an open multicenter study(16) of 163 patients given 400 mg of SAMe per day showed a reduction in depressive symptoms at seven and 15 days. No serious side effects were observed. In their conclusion, the authors recommended that further double-blind trials be undertaken. Again, no documentation of long-term effectiveness or side effects has been reported. Finally, another review(17) concluded that SAMe seemed to have enough of an antidepressant effect to warrant further research.

In conclusion, because no studies have yet validated the long-term safety or efficacy of SAMe, further large long-term studies should be conducted before it receives widespread recommendation.

Diabetes Mellitus

The search for a cure for diabetes mellitus continues along traditional and alternative medicine fronts. Many herbal supplements have been used for the treatment of diabetes, but not all of them have scientific evidence to support their effectiveness. Bitter melon (Momordica charantia), fenugreek and soybeans have been studied as possible treatments in patients with diabetes, but the results of these studies were inconclusive or showed these products to be ineffective.(18-20) A summary of natural products used in the treatment of diabetes is given in Table 2.

CHROMIUM PICOLINATE

Chromium picolinate is a commonly used nutritional supplement marketed in supranutritional dosages for the treatment of diabetes mellitus. It was discovered to have a hypoglycemic effect when added to the total parenteral nutrition given to diabetic patients in intensive care units.(21) Subsequent animal studies revealed similar antidiabetic effects. There are also case reports in the medical literature that support its use in patients with type 1 diabetes mellitus (formerly known as insulin-dependent diabetes mellitus).(22) The rationale for the use of chromium in type 2 diabetes mellitus (formerly known as non-insulin-dependent diabetes mellitus) stems from the fact that patients with type 2 diabetes lose more chromium in the urine than nondiabetic individuals; this phenomenon is thought to contribute to insulin resistance.(23) A study involving 17 patients demonstrated that diets low in chromium may have negative effects on glucose tolerance in patients with borderline diabetes.(24)

While some studies have not demonstrated that chromium has any positive effect on serum glucose levels in humans,(25) other placebo-controlled studies performed in China show beneficial effects when used in patients with type 2 diabetes.(26) In one U.S. study of 180 patients with type 2 diabetes,(27) subjects were subdivided into three groups: a placebo group and two groups taking different dosages of chromium supplements (i.e., 100 [micro]g twice daily or 500 [micro]g twice daily). Patients continued their usual medications and diet. At two months, the group receiving 500 [micro]g of chromium picolinate twice a day experienced significant improvements in glycosylated hemoglobin (HbA1c) compared with the placebo group. After four months, subjects in both treatment groups had improved glucose levels, compared with the placebo group.(27)

Although initial human studies show positive effects, more studies are needed before chromium can be recommended as a supplement to improve serum glucose levels in patients with diabetes.

GARLIC

Many studies involving garlic have shown improved diabetes control in animals.(28) S-allylcysteine sulfoxide, an active ingredient of garlic, was administered to alloxan-diabetic rats for a month, and their conditions improved compared with rats treated with glyburide and insulin.(29) In another study, treatment of alloxan-diabetic rats with antioxidant S-allylcysteine sulfoxide isolated from garlic improved the diabetic condition to the same extent as glyburide and insulin.(30) One possible mechanism of action of garlic on serum glucose may be direct: it may increase the pancreatic secretion of insulin from beta cells, or it may enhance insulin’s release from its bound state.(31) Other authors(32) have suggested an associated insulin-sparing action. The only study(33) identified using humans was a double-blind, randomized trial of 20 patients with type 2 diabetes performed in Thailand. The study did not show glucose-lowering effects of garlic compared with placebo. More human studies are needed before garlic supplements can be recommended for diabetic patients.

ALPHA LIPOIC ACID

This fat-soluble, vitamin-like antioxidant is approved in Germany for treatment of diabetic neuropathy. It is found in liver, potatoes, broccoli and skeletal muscle. Alpha lipoic acid has no effect on levels of fasting serum glucose or HbA1c.

Animal studies have shown alpha lipoic acid to prevent nerve dysfunction, increase blood flow to nerves, help neural regeneration and improve distal nerve conduction rates.(34)

Subsequent human studies were conducted with the following results. In one study,(35) 328 patients with type 2 diabetes and symptomatic diabetic neuropathy were randomly assigned to treatment with intravenous doses of alpha lipoic acid: three doses of 1,200 mg, 600 mg or 100 mg of alpha lipoic acid per day or placebo taken over a three-week period. Symptoms measured included pain, burning, paresthesia and numbness in the feet. The total symptom score of the subjects decreased remarkably in the groups taking 600 mg and 1,200 mg, compared with the placebo group.

Another randomized, double-blind, placebo-controlled multicenter trial(36) was designed to evaluate the efficacy and safety of oral alpha lipoic acid on cardiac autonomic neuropathy in patients with type 2 diabetes. The four-month study included 39 patients who took 800 mg per day of alpha lipoic acid and 34 patients who received placebo. Results indicated that alpha lipoic acid may slightly improve cardiac autonomic neuropathy in diabetic patients.

Hence, the current literature supports the use of alpha lipoic acid in diabetic neuropathy, but more studies are needed.

Obesity

There are many antiobesity products on the market. Some of these products contain ma huang and guarana. A summary of natural products used in the management of obesity is given in Table 3.

MA HUANG

Ma huang contains ephedra, a compound that is similar to ephedrine and has similar effects. The chemical structure of the natural form of ephedrine is levorotatory, while the synthetic ephedrine is a racemic mixture. Ephedra has been shown to increase heart rate, affect blood pressure variably and increase 24-hour energy expenditure in humans.(37) These effects are probably associated with the thermogenic effect of direct beta1 and beta2 agonism.(38)

GUARANA

Guarana is used by Brazilian Indians in a stimulating beverage similar to coffee or tea. It contains an exceptionally high level of caffeine, ranging from 3 to 5 percent by dry weight. In comparison, coffee beans contain approximately 1 to 2 percent caffeine, and dried tea leaves contain 1 to 4 percent caffeine.

MA HUANG AND GUARANA COMBINATIONS

No published studies have evaluated the potential for weight loss with guarana or ma huang. However, two unpublished studies have evaluated the effect of a ma huang/ guarana combination (Metabolife).(39) The first study showed a slight (3 to 6 percent) increase in metabolic rate over a 24-hour period but did not address weight loss. The second study, an eight-week trial of 60 patients, revealed that the combination promoted greater weight loss than placebo but stated that the study was too short to conclude anything about long-term efficacy or safety.(39)

In contrast to ma huang and guarana, much study has been devoted to caffeine and ephedrine. These two products used alone show no benefit in weight loss but appear to be beneficial when used in combination, although not without side effects. Ephedrine/ caffeine combinations have been shown to reduce food intake, increase energy expenditure and decrease weight and body fat in animals.(40) These findings have been corroborated in human open trials and human, randomized, double-blind, placebo-controlled trials.(41)

A randomized, double-blind, placebo-controlled study(42) of 180 obese patients showed significantly greater weight loss with combination ephedrine/caffeine (20 mg/200 mg) over a 24-week period than with placebo.

One study found that 54 percent of patients treated with 20 mg/200 mg of ephedrine/caffeine experienced central nervous system side effects, especially agitation, but noted that these side effects declined markedly after the first month of treatment.(43) In another study, the hemodynamic side effects of an ephedrine/caffeine combination (increased systolic but not diastolic blood pressure, increased heart rate) were transient while the thermogenic effects on energy expenditure were persistent.(44)

Finally, it should be remembered that ephedra has been linked to numerous episodes of toxicity, including 17 deaths.(45) In addition to these published reports attributing sudden death to ma huang, there has also been a case report of hepatotoxicity, presumably associated with an unidentified contaminant in a ma huang product, and a case report of kidney stones induced by ma huang.(46,47) No clinically relevant withdrawal symptoms were observed when subjects were discontinued from 20 mg/200 mg ephedrine/caffeine.(41)

In conclusion, although the weight loss effects of ma huang/guarana combinations have not been completely studied, the public continues to buy these products at an astonishing rate. We must be aware of the potential for beneficial effects as well as adverse effects of these diet aids.

HYDROXYCITRIC ACID/GARCINIA

Among other weight loss alternatives, hydroxycitric acid is often sold as the natural product garcinia. It is found in at least 14 over-the-counter weight loss products and has been shown to inhibit the enzymes that convert citrate into coenzyme A, essentially preventing the body from storing excess energy as fat. It has also been shown to inhibit appetite and reduce food intake in rats.(48)

One well-designed, double-blind, placebo-controlled study of the use of garcinia in humans has been published.(49) This study found that garcinia was no more effective than placebo at the usual commercially available dose. The study has been faulted by some for measuring neither the appetite suppressant effect nor the bioavailability of hydroxycitric acid to the bloodstream. Opponents have postulated that the high-fiber diet used in the study may have limited the bioavailability, thus rendering the study ineffective and leading to the disappointing results.(48) To date, however, the best available data indicate that this product is no more effective than placebo.

GUGGUL GUM (GUGULIPID)

This resin from the myrrh species, in addition to being used as a cholesterol-lowering agent, is found in some over-the-counter diet products. It has been shown to stimulate the release of endogenous thyroid hormone in rats.(50) We have found no studies supporting this claim in human or additional animal studies.

A list of resources for information about alternative therapies is given in Table 4.

REFERENCES

(1.) Herbal Rx: the promises and the pitfalls. Consum Rep 1999;64:44-8.

(2.) Cupp MJ. Herbal remedies: adverse effects and drug interactions. Am Fam Physician 1999;59:1239-45.

(3.) Zink T, Chaffin J. Herbal ‘health’ products: what family physicians need to know. Am Fam Physician 1998;58:1133-40 [published erratum appears in Am Fam Physician 1999;59:540].

(4.) Bennett DA Jr, Phun L, Polk JF, Voglino SA, Zlotnik V, Raffa RB. Neuropharmacology of St. John’s wort (hypericum). Ann Pharmacother 1998;32:1201-8.

(5.) Vorbach EU, Hubner WD, Arnoldt KH. Effectiveness and tolerance of the hypericum extract LI 160 in comparison with imipramine: randomized double-blind study with 135 outpatients. J Geriatr Psychiatry Neurol 1994;7(suppl 1):S19-23.

(6.) Wheatley D. LI 160, an extract of St. John’s wort, versus amitriptyline in mildly to moderately depressed outpatients–a controlled 6-week clinical trial. Pharmacopsychiatry 1997;30(suppl 2):77-80.

(7.) Nordfors M, Hartvig P. St John’s wort against depression in favour again. Lakartidningen 1997; 94:2365-7.

(8.) Piscitelli SC, Burstein AH, Chai HD, Alfaro RM, Falloon J. Indinavir concentrations and St. John’s wort. Lancet 2000;355:547-8.

(9.) Fugh-Berman A. Herb-drug interactions. Lancet 2000;355:134-8.

(10.) Stevinson C, Ernst E. Hypericum for depression. An update of the clinical evidence. Eur Neuropsychopharmacol 1999;9:501-5.

(11.) Linde K, Ramirez G, Mulrow CD, Pauls A, Weidenhammer W, Melchart D. St. John’s wort for depression–an overview and meta-analysis of randomised clinical trials. BMJ 1996;313:253-8.

(12.) Fava M, Rosenbaum JF, MacLaughlin R, Falk WE, Pollack MH, Cohen LS, et al. Neuroendocrine effects of S-adenosyl-L-methionine, a novel putative antidepressant. J Psychiatr Res 1990;24:177-84.

(13.) Young SN. The use of diet and dietary components in the study of factors controlling affect in humans: a review. J Psychiatry Neurosci 1993;18:235-44.

(14.) Bressa GM. S-adenosyl-l-methionine (SAMe) as antidepressant: meta-analysis of clinical studies. Acta Neurol Scand Suppl 1994;154:7-14.

(15.) Bell KM, Potkin SG, Carreon D, Plon L. S-adenosyl-L-methionine blood levels in major depression: changes with drug treatment. Acta Neurol Scand Suppl 1994;154:15-8.

(16.) Fava M, Giannelli A, Rapisarda V, Patralia A, Guaraldi GP. Rapidity of onset of the antidepressant effect of parenteral S-adenosyl-L-methionine. Psychiatry Res 1995;56:295-7.

(17.) Fugh-Berman A, Cott JM. Dietary supplements and natural products as psychotherapeutic agents. Psychosom Med 1999;61:712-28.

(18.) Welihinda J, Karunanayake EH, Sheriff MH, Jayasinghe KS. Effect of Momordica charantia on the glucose tolerance in maturity onset diabetes. J Ethnopharmacol 1986;17:277-82.

(19.) Madar Z, Abel R, Samish S, Arad J. Glucose-lowering effect of fenugreek in non-insulin dependent diabetes. Eur J Clin Nutr 1988;42:51-4.

(20.) Librenti MC, Cocchi MI, Orsi E, Pozza G, Micossi P. Effect of soya and cellulose fibers on postprandial glycemic response in type II diabetic patients. Diabetes Care 1992;15:111-3.

(21.) Freund H, Atamian S, Fischer JE. Chromium deficiency during total parenteral nutrition. JAMA 1979;241:496-8.

(22.) Fox GN, Sabovic Z. Chromium picolinate supplementation for diabetes mellitus. J Fam Pract 1998;46:83-6.

(23.) Morris BW, Macneil S, Hardist CA, Heller S, Burgin C, Gray TA. Chromium homeostasis in patients with type II (NIDDM) diabetes. J Trace Elem Med Biol 1999;13:57-61.

(24.) Anderson RA, Polansky MM, Bryden NA, Canary JJ. Supplemental chromium effects on glucose, insulin, glucagon, and urinary chromium losses in subjects consuming controlled low-chromium diets. Am J Clin Nutr 1991;54:909-16.

(25.) Mannering GJ, Shoeman JA, Shoeman DW. Effects of colupulone, a component of hops and brewers yeast, and chromium on glucose tolerance and hepatic cytochrome P450 in nondiabetic and spontaneously diabetic mice. Biochem Biophys Res Commun 1994;200:1455-62.

(26.) Hellerstein MK. Is chromium supplementation effective in managing type II diabetes? Nutr Rev 1998;56(10):302-6.

(27.) Anderson RA, Cheng N, Bryden NA, Polansky MM, Cheng N, Chi J, et al. Elevated intakes of supplemental chromium improve glucose and insulin variables in individuals with type 2 diabetes. Diabetes 1997;46:1786-91.

(28.) Swanston-Flatt SK, Day C, Bailey CJ, Flatt PR. Traditional plant treatments for diabetes. Studies in normal and streptozotocin diabetic mice. Diabetologia 1990;33:462-4.

(29.) Sheela CG, Kumud K, Augusti KT. Anti-diabetic effects of onion and garlic sulfoxide amino acids in rats. Planta Med 1995;61:356-7.

(30.) Augusti KT, Sheela CG. Antiperoxide effect of S-allylcysteine sulfoxide, an insulin secretagogue, in diabetic rats. Experientia 1996;52:115-20.

(31.) Jain RC, Vyas CR. Garlic in alloxan-induced diabetic rabbits. Am J Clin Nutr 1975;28:684-5.

(32.) Augusti KT. Studies on the effect of allicin (diallyl disulphide-oxide) on alloxan diabetes. Experientia 1975;31:1263-5.

(33.) Sitprija S, Plengvidhya C, Kangkaya V, Bhuvapanich S, Tunkayoon M. Garlic and diabetes melitus phase II clinical trial. J Med Assoc Thai 1987;70(suppl 2):223-7.

(34.) Nagamatsu M, Nickander KK, Schmelzer JD, Raya A, Wittrock DA, Tritschler H, Low PA. Lipoic acid improves nerve blood flow, reduces oxidative stress, and improves distal nerve conduction in experimental diabetic neuropathy. Diabetes Care 1995;18:1160-7.

(35.) Ziegler D, Schatz H, Conrad F, Gries FA, Ulrich H, Reichel G. Effects of treatment with the antioxidant alpha-lipoic acid on cardiac autonomic neuropathy in NIDDM patients. A 4-month randomized controlled multicenter trial (DEKAN Study). Diabetes Care 1997;20:369-73.

(36.) Ziegler D, Gries FA. Alpha-lipoic acid in the treatment of diabetic peripheral and cardiac autonomic neuropathy. Diabetes 1997;46(suppl 2):S62-6.

(37.) White LM, Gardner SF, Gurley BJ, Marx MA, Wang PL, Estes M. Pharmacokinetics and cardiovascular effects of ma-huang (Ephedra sinica) in normotensive adults. J Clin Pharmacol 1997;37:116-22.

(38.) Shannon JR, Gottesdiener K, Jordan J, Chen K, Flattery S, Larson PJ, et al. Acute effect of ephedrine on 24-h energy balance. Clin Sci (Colch) 1999;96:483-91.

(39.) Reno J, Leland J. Heavy meddling (news). Newsweek 1999;134:56-7,59.

(40.) Ramsey JJ, Colman RJ, Swick AG, Kemnitz JW. Energy expenditure, body composition, and glucose metabolism in lean and obese rhesus monkeys treated with ephedrine and caffeine. Am J Clin Nutr 1998;68:42-51.

(41.) Toubro S, Astrup A, Breum L, Quaade F. The acute and chronic effects of ephedrine/caffeine mixtures on energy expenditure and glucose metabolism in humans. Int J Obes Relat Metab Disord 1993; 17(suppl 3):S73-7;discussion S82.

(42.) Astrup A, Breum L, Toubro S, Hein P, Quaade F. The effect and safety of an ephedrine/caffeine compound compared to ephedrine, caffeine and placebo in obese subjects on an energy restricted diet. A double blind trial. Int J Obes Relat Metab Disord 1992;16:269-77.

(43.) Breum L, Pedersen JK, Ahlstrom F, Frimodt-Moller J. Comparison of an ephedrine/caffeine combination and dexfenfluramine in the treatment of obesity. A double-blind multi-centre trial in general practice. Int J Obes Relat Metab Disord 1994;18:99-103.

(44.) Astrup A, Toubro S. Thermogenic, metabolic, and cardiovascular responses to ephedrine and caffeine in man. Int J Obes Relat Metab Disord 1993; 17(suppl 1):S41-3.

(45.) Gurley BJ, Gardner SF, White LM, Wang PL. Ephedrine pharmacokinetics after the ingestion of nutritional supplements containing Ephedra sinica (ma huang). Ther Drug Monit 1998;20:439-45.

(46.) Nadir A, Agrawal S, King PD, Marshall JB. Acute hepatitis associated with the use of a Chinese herbal product, ma-huang. Am J Gastroenterol 1996;91:1436-8.

(47.) Powell T, Hsu FF, Turk J, Hruska K. Ma-huang strikes again: ephedrine nephrolithiasis. Am J Kidney Dis 1998;32:153-9.

(48.) Firenzuoli F, Gori L. Garcinia cambogia for weight loss. JAMA 1999;282:234.

(49.) Heymsfield SB, Allison DB, Vasselli JR, Pietrobelli A, Greenfield D, Nunez C. Garcinia cambogia (hydroxycitric acid) as a potential antiobesity agent: a randomized controlled trial. JAMA 1998;280:1596-600.

(50.) Tripathi YB, Malhotra OP, Tripathi SN. Thyroid stimulating action of Z-guggulsterone obtained from Commiphora mukul. Planta Med 1984;1:78-80.

VINCENT MORELLI, M.D., is an assistant professor in the Department of Family Medicine at the Louisiana State University School of Medicine in New Orleans. He received his medical degree from the University of Southern California School of Medicine, Los Angeles, and completed a residency in family practice at Whittier/USC and a fellowship in sports medicine and arthroscopy in Jonkoping Hospital, Sweden.

ROGER J. ZOOROB, M.D., M.P.H., is the associate department chair of the Department of Family Medicine and the program director of the family practice residency program, Louisiana State University School of Medicine. He received his medical degree and his master’s of public health from the American University of Beirut. Dr. Zoorob completed a residency in family practice at Anderson Memorial Hospital in Anderson, South Carolina and a fellowship in faculty development at the University of Kentucky College of Medicine, Lexington.

Address correspondence to Vincent Morelli, M.D., LSU Health Sciences Center Family Practice Residency Program, 200 W. Esplanade Ave., Ste. 510, Kenner, LA 70065. Reprints are not available from the authors.

TABLE 1

Summary of Natural Products Used in the Treatment of Depression

Product Other names Efficacy

St. John’s Hypericum perforatum, Works as well as

hardhay, amber, TCAs for mild or

goatweed, Klamath moderate depression

weed, Tipton weed

SAMe S-adenosylmethionine; Possibly efficacious;

AdoMet poorly studied;

cost prohibitive

Product Mechanism of action Formulation

St. John’s Acts as weak SSRI, Dried seeds, leaves

dopaminergic, MAOI and flowers; capsule

and norepinephrine

uptake inhibitor

SAMe Methyldonor important Synthetic form of a

in neurotransmitter natural metabolite

synthesis of the amino acid

methionine; tablet

Product Dosage[*] Side effects

St. John’s 300 mg 3 Rare photo-

times daily sensitivity rashcontribute

to serotonin

if used with SSRIs/TCAs/MAOIs/

dopamine agonists; may lower

blood levels of protease inhibitors;

may interfere with drugs used

in organ transplantation

SAMe 400 to 1,200 None recorded

mg per day

Product Drug interactions

St. John’s May lower digoxin level 25%; may

wort

SAMe None recorded

TCA = tricyclic antidepressant; SSRI = selective serotonergic

reuptake inhibitor; MAOI = monoamine oxidase inhibitor.

[*]—Dosages in products may vary considerably.

TABLE 2

Summary of Natural Products Used in the Treatment of Diabetes

Product Other names Efficacy

Chromium None Somewhat efficacious;

possibly needs more

study

Garlic Allium sativum, None to date; few

poor man’s human studies

treacle

Alpha lipoic Thioctic acid Efficacious in decreasing

acid symptoms of diabetic

neuropathy

Product Mechanism of action Formulation

Chromium Counteracts insulin Picolinate (organic form);

resistance; increases capsule/tablet

insulin receptor sensitivity

Garlic May increase secretion Fresh, oil, aqueous,

of insulin fermented or dried

Alpha lipoic Antioxidant Capsule

acid

Product Dosage[*] Side effects

Chromium 50 to 1,000 Indigestion; case reports of

[micro] g per day renal failure with high doses

Garlic Varies None recorded

Alpha lipoic 600 to 1,200 None recorded

acid mg per day

Product Drug interactions

Chromium None recorded

Garlic None recorded

Alpha lipoic None recorded

acid

[*]–Dosages in products may vary considerably.

TABLE 3

Summary of Natural Products Used in the Treatment of Obesity

Product Other names Efficacy

Ma huang Ephedra, desert Possibly effective when

herb, ephedrine used with guarana,

but poorly studied

Guarana Paullinia cupana, Possibly effective when

Brazilian cocoa, used with ma huang,

guarana bread but poorly studied

Ephedrine/ Effective in studies

caffeine up to 1 year

Garcinia Garcinia hanburyi, Not efficacious

Camboge, Gutta

Cambodia, Tom

Rong, Gambodia

Guggul gum Guggal resin, didin, Not studied

didthin, gugalipid

Product Mechanism of action Formulation

Ma huang Stimulant; naturally Dried branchlets;

occurring ephedrine extract; tablet

Guarana Stimulant; naturally Seeds ground and

occurring caffeine dried or roasted;

paste to stick

form; capsule

Ephedrine/ Decreased appetite; Varies

caffeine increased metabolic

rate

Garcinia Said to prevent body Resin dried to

from storing fat powder

Guggul gum Said to release Extract; powdered

endogenous thyroid resin; concentrated

hormone tablets

Product Dosage[*] Side effects

Ma huang 20 mg ma huang/200 Same as ephedrine (e.g.,

mg caffeine equivalent tremor, agitation, insomnia,

3 times daily usually transient); linked

to 17 cardiac deaths

Guarana Guarana dosed as 200 Same as caffeine

mg caffeine equivalent/

20 mg ma huang

3 times daily

Ephedrine/ 20 mg/200 mg Transient (8 weeks) mild

caffeine 3 times daily tremor, agitation, insomnia

Garcinia None recorded Strong laxative effect,

possible abdominal

pain and vomiting at

[greater than] 0.2 g

Guggul gum None recorded None reported

Product Drug interactions

Ma huang Same as ephedrine;

additive effects

with other

stimulants

Guarana Same as caffeine;

additive effects

with other

stimulants

Ephedrine/ Additive effects

caffeine with other

stimulants

Garcinia None recorded

Guggul gum None recorded

[*]—Dosages in products may vary considerably.

TABLE 4

Resources for Information About Alternative Therapies

Some alternative/complementary medicine

Web sites[*] that may be useful to family

physicians are:

Alternative Medicine Foundation

http://www.amfoundation.org/

The NCCAM Complementary and Alternative

Medicine (CAM) Citation Index (CI)

http://nccam.nih.gov/nccam/resources/cam-ci/

American Botanical Council

http://www.herbalgram.org/

Complementary and Alternative Medicine

Program at Stanford (CAMPS)

http://scrdp.stanford.edu/camps.html

Center for Complementary and Alternative Medicine

Research in Asthma, located at the University

of California, Davis

http://www-camra.ucdavis.edu/

An extended list of relevant Web sites is also available

in the October 1999 newsletter

The Review of Natural Products (see below).

In addition, the following publications

are recommended:

La Puma J, ed. Alternative Medicine Alert. Chicago: American

Health Consultants, Inc., 2000.

(http://www.ahcpub.com)

Prescriber’s Letter. Stockton, Calif.:

Therapeutic Research Center, 2000.

(http://www.prescribersletter.com)

The Review of Natural Products. St. Louis, Mo.: Facts and Comparisons, 2000.

(Telephone: 800-223-0554)

PDR for Herbal Medicines. 1st ed. Montvale, N.J.: Medical Economics, 1998.

(http://www.worldimage.com/books/pdrforherbalmedicines.html)

[*]–These Web sites were verified August 2, 2000.

COPYRIGHT 2000 American Academy of Family Physicians

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