Lithium Carbonate

Brand Names: Eskalith, Lithobid, Lithonate, Lithotabs

Clinical Names: Lithium Carbonate

Summary

generic name: Lithium

chemical name: Lithium carbonate

trade name: Eskalith®, Lithobid®, Lithonate®,  Lithotabs®

type of drug: Anti-depressant, anti-manic.

used to treat: Bipolar disorder (manic-depression) and severe depression.

Note: Lithium is not commonly used as a supplemental nutrient though it may have value in such a role. Links to Lithium will reference this entry as there is no separate entry for Lithium in the Nutrients section.

overview of interactions:
• nutrient affecting drug performance: Chromium

• nutrient affected by drug: Magnesium

• nutrient affecting drug performance: Sodium

• herb affecting drug performance: Gymnema sylvestre (Gymnema leaves)

• herb affecting drug performance: Momordica charantia (Bitter Melon or Karela)

• herb affecting drug performance: Trigonella foenum-graecum (Fenugreek seeds)

• foods/herbs affecting drug performance: Hypoglycemic Herbs including Allium cepa (Onion bulbs), Allium sativum (Garlic cloves), Anacardium occidentale (Cashew leaves), Arctium lappa (Burdock root), Catharanthus roseus (Madagascar Periwinkle leaves), Cuminum cyminum (Cumin seed), Eleutherococcus senticosus (Siberian Ginseng), Galega officinalis (Goat’s Rue seeds), Gymnema sylvestre (Gymnema leaves), Momordica charantia (Bitter Melon fruit), Olea europaea (Olive leaves), Oplopanax horridum (Devil’s Club bark), Opuntia spp. (Prickly Pear stems and fruit), Panax ginseng (Chinese Ginseng root), Phaseolus vulgaris (Kidney bean, immature pods), Taraxacum officinale (Dandelion plant), Trigonella foenum-graecum (Fenugreek seeds), Urtica dioica (Stinging Nettle plant), Vaccinium myrtillus (Bilberry leaves).

• foods/herbs affecting drug performance: Psyllium Plantago, Plantago ovata (Psyllium) - Hydrophilic Fiber

• food/herbal constituent affecting drug performance and toxicity: Caffeine, Coffea arabica (Coffee)

• foods affecting drug toxicity: Food

• foods affecting drug performance: Urine-Alkalinizing Foods



Interactions

nutrient affecting drug performance: Chromium

• mechanism: Lithium carbonate has been found to reduce blood glucose levels in diabetics. Chromium potentiates the action of insulin. The combined effect of two substances with potential hypoglycemic action might present a significant risk for excessively low blood glucose levels.
(Hu M, et al. Biol Trace Elem Res 1997 Oct-Nov;60(1-2):131-137; Mertz W. Nutr Rev 1998 Jun;56(6):174-177.)

• nutritional synergy: Chromium's ability to enhance endogenous regulation of blood glucose levels, together with its potentiation of insulin, make it a valuable tool in stabilizing diabetic degeneration and eventually reducing dependence on insulin. However, consultation with the prescribing physician and close monitoring of blood glucose levels is recommended for any individual on lithium who is considering supplementation with chromium, especially if they have a history of hypoglycemia or have also been prescribed insulin. Physicians experienced in nutritional therapy typically prescribe chromium at a dosage of 200 mcg, 1-2 times daily; chromium picolinate is the preferred form.

nutrient affected by drug: Magnesium

• mechanism: Magnesium and lithium are chemically related. The consumption of lithium carbonate may cause high blood levels of magnesium.
(Herzberg L, Herzeberg B. J Nerv Ment Dis. 1977 Dec;165(6):423-426; Nielsen J. Acta Psychiatr Scand 1964 40:190-196; Nielsen J. Acta Psychiatr Scand 1964;40:197-202.)

• nutritional concerns: Individuals taking lithium should inform their prescribing physician if they are also supplementing with magnesium. Likewise, the prescribing physician, a pharmacist, and/or a healthcare professional trained in nutrition should be consulted before starting any supplementation with magnesium, separately or as part of a multivitamin-mineral formulation.

nutrient affecting drug performance: Sodium

• mechanism: During the first day of use, lithium may increase excretion of sodium, potassium and water. In the subsequent 4-5 day period sodium may elevate due to increased retention. Sodium metabolism will typically normalize after this initial flux. Beyond this initial phase, lithium causes increased sodium and potassium excretion while renal concentrating ability and water reabsorption are decreased.

• nutritional concerns: Changes in sodium intake may significantly alter the renal elimination of lithium. Salt restriction can be particularly dangerous during the initial twenty-four hour period of lithium use due to depressed sodium levels. Decreasing sodium intake may lead to decreased clearance of lithium and vice versa. While problems with sodium restriction are not common, caution is advised, especially on the first day the lithium is taken. Individuals using lithium should be advised to maintain adequate sodium and fluid intake and to avoid substantial changes in either. They should also be cautioned to avoid dehydration and to report prolonged vomiting, diarrhea or fever to the prescribing physician.

herb affecting drug performance: Gymnema sylvestre (Gymnema leaves)

• research: Several much-cited studies have found that Gymnema sylvestre, a traditional antidiabetic herb from India, can enhance blood sugar stability, increase the activity of key glucose-regulating enzymes, and possibly reverse degenerative changes due to diabetes. Some research finding with rabbits indicates that Gymnema can stimulate the regeneration of the insulin-producing Islets of Langerhans, as well as correct the metabolic derangements in liver, kidney and muscle tissues attributable to diabetes.
(Shanmugasundaram KR, et al. Pharmacol Res Commun 1981 May;13(5):475-486; Shanmugasundaram KR, et al. J Ethnopharmacol 1983 Mar;7(2):205-234; Baskaran K, et al. J Ethnopharmacol 1990 Oct;30(3):295-300; Shanmugasundaram ER, et al. J Ethnopharmacol. 1990 Oct;30(3):281-294.)

• nutritional synergy: The reputation of Gymnema sylvestre has grown steadily over the past decade based on traditional usage and modern research. Correspondingly its usage by the general public and healthcare professionals trained in herbal medicine has become a significant presence in the botanical treatment of blood sugar imbalances and diabetes. Given that lithium carbonate has been found to reduce blood glucose levels in diabetics, caution seems appropriate regarding the simultaneous use of lithium and Gymnema. Most importantly, no research has been conducted as to the aggregate interaction of insulin, lithium and Gymnema among diabetics. Consultation with the prescribing physician is necessary and an integrative management of the case by conventional and herbal practitioners working together would be preferred. Traditionally, indigenous practitioners of India would prescribe 2-4 grams of the leaf per day. The studies conducted in India over the past twenty years have generally used 400 mg per day of GS4, a water-soluble extract of the leaves of Gymnema sylvestre. See further cautionary notes in Hypoglycemic Herbs subtopic below for more information.
(Hu M, et al. Biol Trace Elem Res 1997 Oct-Nov;60(1-2):131-137.)

herb affecting drug performance: Momordica charantia (Bitter Melon or Karela)

• research: Several studies have found that Momordica charantia exerts a hypoglycemic effect. The combination of lithium and Momordica could potentially cause blood glucose levels to drop excessively and would especially be of concern among for diabetic patients. In one human study by Welihinda et al, the fruit juice of M. charantia significantly improved glucose tolerance in 73% of the patients investigated while the other 27% failed to respond. Improvement in glucose tolerance was not associated with an increase in serum insulin responses. These results show that karela improves glucose tolerance in diabetes. Other test results, from research involving rodents, suggest that orally administered karela extracts lower glucose concentrations independently of intestinal glucose absorption and involve an extrapancreatic effect. The data from these various studies, along with in vitro research, indicate that molecules with insulin-like bioactivity are present in Momordica charantia seeds.
(Day C, et al. Planta Med 1990 Oct;56(5):426-429; Leatherdale BA, et al. Br Med J (Clin Res Ed) 1981 Jun 6;282(6279):1823-1824; Ng TB, et al. J Ethnopharmacol 1986 Jan;15(1):107-117; Welihinda J, et al. J Ethnopharmacol 1986 Sep;17(3):277-282.)

• nutritional synergy: Fried bitter melon or karela fruits consumed as a an herbal medicine or as a daily supplement to the diet can produce a small but significant improvement in glucose tolerance. Likewise, lithium carbonate has been found to reduce blood glucose levels in diabetics. The insulin-like action of Momordica charantia make it a potentially valuable tool in stabilizing diabetic degeneration and eventually reducing dependence on insulin. However, consultation with the prescribing physician and close monitoring of blood glucose levels is recommended for any individual on insulin who is considering supplementation with this herb/food, especially in the presence of lithium. Insulin dosage may need adjusting due to hypoglycemic effect in diabetic patients. Thorough inquiry about dietary customs and traditional medical treatments is especially important among Asians where this fruit is commonly consumed as a food and medicine. Ultimately the interaction of lithium and Momordica, and its effect on blood sugar levels, is uncertain and some attendant risk for adverse effects deserves consideration, especially among diabetics or those with hypoglycemia.
(Hu M, et al. Biol Trace Elem Res 1997 Oct-Nov;60(1-2):131-137.)

herb affecting drug performance: Trigonella foenum-graecum (Fenugreek seeds)

• herbal synergy: Several studies have examined the role of fenugreek seeds for use by individuals with insulin-dependent (Type 1) diabetes. In one study of the effect of fenugreek seeds (Trigonella foenum graecum) blood glucose levels improved significantly when the regular insulin therapy was supplemented with 50 grams, twice daily, of defatted fenugreek seeds for ten days. The fenugreek diet significantly reduced fasting blood sugar and improved the glucose tolerance test. Further, this integrative therapy also usually resulted in an improved serum lipid profile with serum total cholesterol, LDL and VLDL cholesterol and triglycerides all significantly reduced. No indications of adverse interactions were apparent and the fenugreek seeds did not appear to interfere with the insulin treatment. Studies with animals have come to similar conclusions.
(Sharma RD, et al. Eur J Clin Nutr 1990 Apr;44(4):301-306; Ali L, et al. Planta Med 1995 Aug;61(4):358-360; Khosla P, et al. Indian J Physiol Pharmacol 1995 Apr;39(2):173-174.)

• foods/herbs affecting drug performance: Hypoglycemic Herbs including Allium cepa (Onion bulbs), Allium sativum (Garlic cloves), Anacardium occidentale (Cashew leaves), Arctium lappa (Burdock root), Catharanthus roseus (Madagascar Periwinkle leaves), Cuminum cyminum (Cumin seed), Eleutherococcus senticosus (Siberian Ginseng), Galega officinalis (Goat’s Rue seeds), Gymnema sylvestre (Gymnema leaves), Momordica charantia (Bitter Melon fruit), Olea europaea (Olive leaves), Oplopanax horridum (Devil’s Club bark), Opuntia spp. (Prickly Pear stems and fruit), Panax ginseng (Chinese Ginseng root), Phaseolus vulgaris (Kidney bean, immature pods), Taraxacum officinale (Dandelion plant), Trigonella foenum-graecum (Fenugreek seeds), Urtica dioica (Stinging Nettle plant), Vaccinium myrtillus (Bilberry leaves).
(See complete listing at the end of the References)
See also: Hyperglycemic/Hypoglycemic Herb Group.

• mechanism: A large number of indigenous plants used as foods and medicines around the world are known for their ability to lower blood sugar levels through a variety of mechanisms. In some instances, the plant's hypoglycemic activity has been attributed to a particular extract or an identified constituent. These plants have often been used by practitioners of herbal medicine in treating individuals with non-insulin-dependent (type 2) diabetes. Further, the use of such herbs by type 1 (insulin-dependent) diabetics can be very risky and requires that such patients carefully monitor their blood sugar to prevent hypoglycemic and hyperglycemic episodes. Consultation with the prescribing physician is necessary and an integrative management of the case by conventional and herbal practitioners working together would be preferred. The shared goal would be to regulate the dosage of both types of medication and enable a smooth transition to lower dependence on insulin in cases where such is desirable and attainable. While hypoglycemic herbs may offer promise in the treatment of diabetes their interaction with lithium, especially in regard to effcts on blood sugar levels, deserves caution. This would be particularly true among insulin-dependent diabetics where the combined effect of lithium and insulin could potentially be disruptive to blood sugar levels and increase risk of insulin shock.

foods/herbs affecting drug performance: Psyllium Plantago, Plantago ovata (Psyllium) - Hydrophilic Fiber

• mechanism: Hydrophilic fiber such as Psyllium can reduce absorption of lithium taken orally.

• reports: There have been reports of individuals taking lithium who experienced decreased lithium levels after they started consuming psyllium husk, in one case two times per day; lithium levels increased to therapeutic levels after stopping the psyllium.
(Toutoungi M, et al. Therapie. 1990 Jul-Aug;45(4):358-60; Perlman BB. Lancet. 1990 Feb 17;335(8686):416.)

• nutritional concerns: Adverse effects from this interaction can usually be avoided by taking the lithium at least one hour before the psyllium.

food/herbal constituent affecting drug performance and toxicity: Caffeine, Coffea arabica (Coffee)

• adverse drug effect: Lithium therapy often produces hand tremor as a side effect. Caffeine can also cause anxiety and tremor.

• report/research: Jefferson reported two cases where women taking lithium experienced increased tremors after they stopped drinking coffee, presumably due to a reduction in renal lithium clearance. One woman had been drinking seventeen cups of coffee per day; her lithium levels showed a 50% increase when she kept taking the lithium but stopped consuming the coffee. She stabilized after her lithium dosage was reduced by 20%. Likewise, Mester et al tracked eleven individuals taking lithium after they stopped consuming an average of four to six cups of coffee per day. They found that the subjects reported a greater incidence of anxiety and depression and demonstrated higher blood levels of lithium within two weeks. Further, lithium levels, as well as ratings on depression and anxiety, returned to their original baseline status two weeks after these subjects returned to their previous coffee consumption patterns.

• dietary concerns: Pending further research, individuals taking lithium should avoid suddenly changing their level of coffee or other sources of caffeine. The reduction of caffeine intake may improve the health and metabolic balance of many individuals suffering from the conditions for which lithium is prescribed, particularly mania. However, the prescribing physician or a pharmacist should be consulted if changes in caffeine consumption patterns are desired or anticipated.
(Jefferson JW. Clin Psychiatry 1988 Feb;49(2):72-73; Mester R, et al. Biol Psychiatry. 1995 Mar 1;37(5):348-350.)

food affecting drug toxicity: Food

• dietary concerns: The digestive upset commonly associated with taking lithium can be avoided by taking the drug with food.
(Yamreudeewong W, et al. J Fam Pract. 1995 Apr;40(4):376-84; Hathcock JN. Fed Proc. 1985 Jan;44(1 Pt 1):124-129.)

foods affecting drug performance: Urine-alkalinizing Foods

• mechanism: The rate of lithium excretion increases in alkaline urine. Consequently consumption of a diet high in foods that produce more alkaline urine is associated with more rapid excretion of lithium and resulting decreased drug effectiveness.

• dietary concerns: Individuals taking lithium should eat a balanced diet and avoid excessive consumption of foods that alkalinize the urine. The foods which have the greatest effect in alkalinizing the urine are dairy products, many nuts (including almonds and chestnuts), a variety of fruits (especially citrus, but not cranberries, plums or prunes), molasses, and vegetables such as beets, kale, mustard greens, spinach, and turnip greens (but not corn and lentils). Individuals taking lithium who are concerned about how their diet may be interacting with their medication should consult their prescribing physician, pharmacist and/or a healthcare professional trained in nutritional therapies.
(Holt GA. 1998, 157; Yamreudeewong W, et al. J Fam Pract. 1995 Apr;40(4):376-84; Hathcock JN. Fed Proc. 1985 Jan;44(1 Pt 1):124-129; Emanuelli G, et al. Enzyme. 1985;34(4):177-185.)


Please read the disclaimer concerning the intent and limitations of the information provided here.
Do not rely solely on the information in this article.

The information presented in Interactions is for informational and educational purposes only. It is based on scientific studies (human, animal, or in vitro), clinical experience, case reports, and/or traditional usage with sources as cited in each topic. The results reported may not necessarily occur in all individuals and different individuals with the same medical conditions with the same symptoms will often require differing treatments. For many of the conditions discussed, treatment with conventional medical therapies, including prescription drugs or over-the-counter medications, is also available. Consult your physician, an appropriately trained healthcare practitioner, and/or pharmacist for any health concern or medical problem before using any herbal products or nutritional supplements or before making any changes in prescribed medications and/or before attempting to independently treat a medical condition using supplements, herbs, remedies, or other forms of self-care.



References

al-Hader AA, Hasan ZA, Aqel MB. Hyperglycemic and insulin release inhibitory effects of Rosmarinus officinalis. J Ethnopharmacol 1994 Jul 22;43(3):217-221.
Abstract: The effects of the volatile oil extracted from the leaves of Rosmarinus officinalis on glucose and insulin levels were investigated in normal rabbits, after the administration of an intraperitoneal glucose tolerance test (GTT). Also, the effects of the volatile oil on fasting plasma glucose levels, were studied in alloxan diabetic rabbits. In normal rabbits, the intramuscular (i.m.) administration of the volatile oil (25 mg/kg) produced 20% (P < 0.05), 27% (P < 0.01) and 55% (P < 0.001) increases in plasma glucose levels, above those of control animals, at the 60, 90 and 120 min intervals, respectively, following the administration of the intraperitoneal (i.p.) glucose test. The same treatment also resulted in a 30% (P < 0.002) decrease in serum insulin level, in comparison with that of control rabbits at the 30 min interval. In alloxan diabetic rabbits, R. officinalis volatile oil increased fasting plasma glucose levels by 17% (P < 0.05) above those of untreated animals 6 h after its administration. These data suggest that the volatile oil of R. officinalis has hyperglycemic and insulin release inhibitory effects in the rabbit.

Ali L, Azad Khan AK, Hassan Z, Mosihuzzaman M, Nahar N, Nasreen T, Nur-e-Alam M, Rokeya B. Characterization of the hypoglycemic effects of Trigonella foenum graecum seed. Planta Med 1995 Aug;61(4):358-360. (Letter)
Abstract: The whole powder of Trigonella foenum graecum seeds and its extracts were tested for their hypoglycemic effect on normal and diabetic model rats. The powder, its methanol extract, and the residue remaining after methanol extraction had significant hypoglycemic effects when fed simultaneously with glucose. The water extract of the methanol extractive-free residue of the seed powder showed significant hypoglycemic activity at different prandial states. The Soluble Dietary Fibre (SDF) fraction showed no effect on the fasting blood glucose levels of nondiabetic or NIDDM model rats. However, when fed simultaneously with glucose, it showed a significant hypoglycemic effect (p < 0.05) in NIDDM model rats. Chemical analysis showed that the major constituent of the SDF is a galactomannan. The results confirm the involvement of SDF in the hypoglycemic effect of T. foenum graecum seeds. However, compound(s) other than SDF is (are) also involved in the hypoglycemic activity.

American Herbal Products Association. Botanical Safety Handbook. CRC Press: Boca Raton, FL, 1997.

Baldessarinin RI. Drugs and the treatment of psychiatric disorders. In Goodman and Gilman's The Pharmacologicol Basis of Therapeutics, 6th ed., A Goodman Gilman, LS Goodman, A Gilman, eds. New York: Macmillan, 1980, 433. (Review).

Baskaran K, Ahmath BK, Shanmugasundaram KR, Shanmugasundaram ERB. Antidiabetic effect of a leaf extract from Gymnema sylvestre in non-insulin-dependent diabetes mellitus patients. J Ethnopharmacol 1990 Oct;30(3):295-300.
Abstract: The effectiveness of GS4, an extract from the leaves of Gymnema sylvestre, in controlling hyperglycaemia was investigated in 22 Type 2 diabetic patients on conventional oral anti-hyperglycaemic agents. GS4 (400 mg/day) was administered for 18-20 months as a supplement to the conventional oral drugs. During GS4 supplementation, the patients showed a significant reduction in blood glucose, glycosylated haemoglobin and glycosylated plasma proteins, and conventional drug dosage could be decreased. Five of the 22 diabetic patients were able to discontinue their conventional drug and maintain their blood glucose homeostasis with GS4 alone. These data suggest that the beta cells may be regenerated/repaired in Type 2 diabetic patients on GS4 supplementation. This is supported by the appearance of raised insulin levels in the serum of patients after GS4 supplementation.

Bever BO, Zahnd GR. Plants with Oral Hypoglycaemic Action. Quart. J Crude Drug Res 1979;17:139-196.

Brinker F. Botanical Medicine Research Summaries. In: Eclectic Dispensatory of Botanical Therapeutics, Vol. II. Eclectic Medical Publications: Sandy, OR, 1995.

Brinker F. Herb Contraindications and Drug Interactions. Eclectic Institute: Sandy, OR, 1997.

Day C, Cartwright T, Provost J, Bailey CJ. Hypoglycaemic effect of Momordica charantia extracts. Planta Med 1990 Oct;56(5):426-429.
Abstract: The hypoglycaemic effect of orally administered extracts of fruits of cultivated Momordica charantia (karela) was examined in normal and streptozotocin diabetic mice. In normal mice, an aqueous extract (A) lowered the glycaemic response to both oral and intraperitoneal glucose, without altering the insulin response. This aqueous extract (A) and the residue after alkaline chloroform extraction (B) reduced the hyperglycaemia in diabetic mice at 1 hour. Material recovered by acid water wash of the chloroform extract remaining after an alkaline water wash (D) produced a more slowly generated hypoglycaemic effect. The results suggest that orally administered karela extracts lower glucose concentrations independently of intestinal glucose absorption and involve an extrapancreatic effect. Two types of hypoglycaemic substances with different time dependent effects are indicated.

Emanuelli G, Anfossi G, Calcamuggi G, Marcarino C, Ottone G, Dughera L. Urinary enzyme excretion in acute and subacute experimental lithium administration. Enzyme. 1985;34(4):177-185.

Farnsworth, NR, Segelman, AB. Hypoglycemic Plants. Tile Till 57:52-56, 1971.

Gonzalez M, Zarzuelo A, Gamez MJ, Utrilla MP, Jimenez J, Osuna I. Hypoglycemic activity of olive leaf. Planta Med 1992 Dec;58(6):513-515.
Abstract: The hypoglycemic activity of olive leaf was studied. Maximum hypoglycemic activity was obtained from samples collected in the winter months, especially in February. One of the compounds responsible for this activity was oleuropeoside, which showed activity at a dose of 16 mg/kg. This compound also demonstrated antidiabetic activity in animals with alloxan-induced diabetes. The hypoglycemic activity of this compound may result from two mechanisms: (a) potentiation of glucose-induced insulin release, and (b) increased peripheral uptake of glucose.

Hathcock JN. Metabolic mechanisms of drug-nutrient interactions. Fed Proc. 1985 Jan;44(1 Pt 1):124-129. (Review)

Herzberg L, Herzeberg B. Mood change and magnesium. A possible interaction between magnesium and lithium? J Nerv Ment Dis. 1977 Dec;165(6):423-426.
Abstract: Magnesium and lithium are chemically related. Magnesium is an essential ion in many enzyme systems and lithium is of value in the treatment of manic-depressive disease. A significant sex difference in mean plasma magnesium levels is reported in 44 depressed patients. It is suggested that further studies of magnesium metabolism are indicated and that they may provide a better understanding of manic-depressive disease and the mode of action of lithium.

Hu M, Wu H, Chao C. Assisting effects of lithium on hypoglycemic treatment in patients with diabetes. Biol Trace Elem Res 1997 Oct-Nov;60(1-2):131-137.
Abstract: In this article, we report the assisting effect of lithium on hypoglycemic treatment in patients with diabetes. Thirty-eight diabetic patients, 15 male and 23 female, aged 20-70 yr, 33 noninsulin-dependent diabetes mellitus (NIDDM) patients, and 5 insulin-dependent diabetes mellitus (IDDM) patients, were recruited in this study. Fasting and 1-h postprandial blood glucose (BG) profiles were undertaken from three groups of patients with diabetes before and after short-term of treatment of lithium carbonate. Group I was treated with diet only, Group II with oral hypoglycemic agents (OHA), and Group III with insulin. The fasting blood glucose (FBG) level and 1-h postprandial blood glucose (1-h PBG) level before and after treatment of lithium were: Group I: FBG: 7.67 +/- 0.48 vs. 7.13 +/- 0.82; 1-h PBG 15.13 +/- 0.88 vs. 10.33 +/- 0.96; Group II: FBG: 8.84 +/- 0.67 vs. 6.04 +/- 0.57; 1-h PBG: 12.33 +/- 0.72 vs. 9.95 +/- 0.82; Group III: FBG: 10.87 +/- 0.83 vs. 6.83 +/- 0.79; 1-h PBG: 12.45 +/- 0.93 vs. 9.17 +/- 1.00 mmol/L, respectively. The FBG and PBG of all three groups decreased significantly after lithium treatment, except the FBG in Group I. These data suggest that combined with other therapy, lithium could improve glucose metabolism in most patients with diabetes. Our results suggest that lithium has an assisting hypoglycemic effect on antidiabetic treatment.

Jefferson JW. Lithium tremor and caffeine intake: two cases of drinking less and shaking more. J Clin Psychiatry 1988 Feb;49(2):72-73.
Abstract: Lithium tremor worsened in two patients when caffeine (coffee) was eliminated from their diets. An associated reduction in renal lithium clearance resulting in increased serum lithium level is thought to be the mechanism.

Khosla P, Gupta DD, Nagpal RK. Effect of Trigonella foenum graecum (Fenugreek) on blood glucose in normal and diabetic rats. Indian J Physiol Pharmacol 1995 Apr;39(2):173-174.
Abstract: Trigonella foenum graecum (Fenugreek) was administered at 2 and 8 g/kg dose orally to normal and alloxan induced diabetic rats. It produced a significant fall (P < 0.05) in blood glucose both in the normal as well as diabetic rats and the hypoglycemic effect was dose related.

Leatherdale BA, Panesar RK, Singh G, Atkins TW, Bailey CJ, Bignell AH. Improvement in glucose tolerance due to Momordica charantia (karela). Br Med J (Clin Res Ed) 1981 Jun 6;282(6279):1823-1824.
Abstract: The effect of karela (Momordica charantia), a fruit indigenous to South America and Asia, on glucose and insulin concentrations was studied in nine non-insulin-dependent diabetics and six non-diabetic laboratory rats. A water-soluble extract of the fruits significantly reduced blood glucose concentrations during a 50 g oral glucose tolerance test in the diabetics and after force-feeding in the rats. Fried karela fruits consumed as a daily supplement to the diet produced a small but significant improvement in glucose tolerance. Improvement in glucose tolerance was not associated with an increase in serum insulin responses. These results show that karela improves glucose tolerance in diabetes. Doctors supervising Asian diabetics should be aware of the fruit's hypoglycaemic properties.

Mertz W. Interaction of chromium with insulin: a progress report. Nutr Rev 1998 Jun;56(6):174-177. (Review)

Mester R, Toren P, Mizrachi I, Wolmer L, Karni N, Weizman A. Caffeine withdrawal increases lithium blood levels. Biol Psychiatry. 1995 Mar 1;37(5):348-350.

Newall, Carol, Anderson, Linda and Phillipson, J. David. Herbal Medicines: A Guide for Health-care Professionals. The Pharmaceutical Press: London, 1996.

Ng TB, Wong CM, Li WW, Yeung HW. Insulin-like molecules in Momordica charantia seeds. J Ethnopharmacol 1986 Jan;15(1):107-117.
Abstract: Decorticated Momordica charantia seeds were extracted and processed by a method which was developed originally for the purification of insect and annelid insulins. Essentially, the method entailed HCl-ethanol extraction, neutralization with NH4OH, gel filtration on Sephadex G-50, ion exchange chromatography on CM Sepharose CL-6B and desalting on Sephadex G-10. Of the seven fractions collected, three fractions were obtained with antilipolytic and lipogenic activities in isolated adipocytes and one fraction with only lipogenic activity. The data indicate that molecules with insulin-like bioactivity are present in Momordica charantia seeds.

Nielsen J. Magnesium-lithium studies. 1. Serum and erythrocyte magnesium in patients with manic states during lithium treatment. Acta Psychiatr Scand 1964 40:190-196.

Nielsen J. Magnesium-lithium studies. 2. The effect of lithium on serum magnesium in rabbits. Acta Psychiatr Scand 1964;40:197-202.

Perlman BB. Interaction between lithium salts and ispaghula husk. Lancet 1990 Feb 17;335(8686):416. (Letter)

Platel K, Srinivasan K. Plant foods in the management of diabetes mellitus: vegetables as potential hypoglycaemic agents. Nahrung 1997 Apr;41(2):68-74. (Review)
Abstract: Vegetables are among the numerous plant adjuncts tried for the treatment of diabetes mellitus. A few vegetables that are commonly consumed in India have been claimed to possess antidiabetic potency. In recent years, there has been a renewed interest to screen such plant food materials, for a possible beneficial use. Considerable amount of work has been carried out in this regard with bitter gourd (Momordica charantia) and ivy gourd (Coccinia indica) both in experimental animals and human diabetic subjects. Majority of these studies have documented the beneficial effect of the fruit of bitter gourd and leaf of ivy gourd when administered orally as a single dose. The hypoglycaemic influence is claimed to be mediated through an insulin secretagogue effect or through an influence on enzymes involved in glucose metabolism. The limited number of studies on other vegetables such as cabbage (Brassica oleracia), green leafy vegetables, beans and tubers have shown the beneficial hypoglycaemic influence in both experimental animals and humans. There is scope for more extensive research in this area, especially to examine the long term beneficial effect of dietary vegetables, to identify the active principle, and to understand the mechanism of action, which is at present unclear. Since diet forms the mainstay in the management of diabetes mellitus, there is scope for exploiting the antidiabetic potency of vegetables to the maximum extent. Such plant food adjuncts possessing hypoglycaemic activity appear to hold promise as potential antidiabetic agents.

Sadhukhan B, Roychowdhury U, Banerjee P, Sen S. Clinical evaluation of a herbal antidiabetic product. J Indian Med Assoc 1994 Apr;92(4):115-117.
Abstract: Sixty-seven diabetic patients and 12 normal subjects were selected for a clinical study with an indigenous herbal product. The study consisted of 2 phases. In phase 1 study out of 25 diabetics (both insulin dependent and non-insulin dependent) only those in the age group of 41-50 years ie, 11 cases showed lowering of mean high blood sugar level in all samples from 1/2 an-hour to 2 hours with the test drug containing guar gum, methi, tundika and mesha shringi. But in phase 2 study there was lowering of blood sugar level with the test drug and with 2 of its constituents ie, guar gum and methi when used separately in 42 non-insulin dependent diabetics. While there was some blood sugar level lowering effect with guar gum and methi when used separately in 12 normal subjects in phase 2 study, but that was not the same observed with the test drug. The results of this study indicate the efficacy of the product as an adjuvant.

Shanmugasundaram KR, Panneerselvam C, Samudram P, Shanmugasundaram ER. The insulinotropic activity of Gymnema sylvestre, R. Br. An Indian medical herb used in controlling diabetes mellitus. Pharmacol Res Commun 1981 May;13(5):475-486.

Shanmugasundaram KR, Panneerselvam C, Samudram P, Shanmugasundaram ER. Enzyme changes and glucose utilisation in diabetic rabbits: the effect of Gymnema sylvestre. R Br J Ethnopharmacol 1983 Mar;7(2):205-234.
Abstract: The administration of the dried leaf powder of Gymnema sylvestre regulates the blood sugar levels in alloxan diabetic rabbits. G. sylvestre therapy not only produced blood glucose homeostasis but also increased the activities of the enzymes affording the utilisation of glucose by insulin dependent pathways: it controlled phosphorylase levels, gluconeogenic enzymes and sorbitol dehydrogenase. The uptake and incorporation of [14C] glucose into the glycogen and protein are increased in the liver, kidney and muscle in G. sylvestre administered diabetic animals when compared to the untreated diabetic animals. Pathological changes initiated in the liver during the hyperglycemic phase are reversed by controlling hyperglycemia by G. sylvestre. G. sylvestre, a herb used for the control of diabetes mellitus in several parts of India, appears to correct the metabolic derangements in diabetic rabbit liver, kidney and muscle.

Sharma RD, Raghuram TC, Rao NS. Effect of fenugreek seeds on blood glucose and serum lipids in type I diabetes. Eur J Clin Nutr 1990 Apr;44(4):301-306.
Abstract: The effect of fenugreek seeds (Trigonella foenum graecum) on blood glucose and the serum lipid profile was evaluated in insulin-dependent (Type I) diabetic patients. Isocaloric diets with and without fenugreek were each given randomly for 10 d. Defatted fenugreek seed powder (100 g), divided into two equal doses, was incorporated into the diet and served during lunch and dinner. The fenugreek diet significantly reduced fasting blood sugar and improved the glucose tolerance test. There was a 54 per cent reduction in 24-h urinary glucose excretion. Serum total cholesterol, LDL and VLDL cholesterol and triglycerides were also significantly reduced. The HDL cholesterol fraction, however, remained unchanged. These results indicate the usefulness of fenugreek seeds in the management of diabetes.

Shanmugasundaram ER, Rajeswari G, Baskaran K, Rajesh Kumar BR, Radha Shanmugasundaram K, Kizar Ahmath B. Use of Gymnema sylvestre leaf extract in the control of blood glucose in insulin-dependent diabetes mellitus. J Ethnopharmacol 1990 Oct;30(3):281-294.
Abstract: GS4, a water-soluble extract of the leaves of Gymnema sylvestre, was administered (400 mg/day) to 27 patients with insulin-dependent diabetes mellitus (IDDM) on insulin therapy. Insulin requirements came down together with fasting blood glucose and glycosylated haemoglobin (HbA1c) and glycosylated plasma protein levels. While serum lipids returned to near normal levels with GS4 therapy, glycosylated haemoglobin and glycosylated plasma protein levels remained higher than controls. IDDM patients on insulin therapy only showed no significant reduction in serum lipids, HbA1c or glycosylated plasma proteins when followed up after 10-12 months. GS4 therapy appears to enhance endogenous insulin, possibly by regeneration/revitalisation of the residual beta cells in insulin-dependent diabetes mellitus.

Shuster J. Lithium and sodium depletion. Teach your patient how to avoid this cause of toxicity. Nursing 1998 Sep;28(9):29.

Stockley IH. Drug Interactions, Fourth Ed. London: Pharmaceutical Press, 1996.

Tandon A, Nagpaul JP, Bandhu H, Singh N, Dhawan DK. Effect of lithium on hepatic and serum elemental status under different dietary protein regimens. Biol Trace Elem Res. 1999 Apr;68(1):51-62.

Toutoungi M, Schulz P, Widmer J, Tissot R. [Probable interaction of psyllium and lithium]. Therapie 1990 Jul-Aug;45(4):358-360. [Article in French] (Letter)

Welihinda J, Karunanayake EH, Sheriff MH, Jayasinghe KS. Effect of Momordica charantia on the glucose tolerance in maturity onset diabetes. J Ethnopharmacol 1986 Sep;17(3):277-282.
Abstract: Investigations were carried out to evaluate the effect of Momordica charantia on the glucose tolerance of maturity onset diabetic patients. The fruit juice of M. charantia was found to significantly improve the glucose tolerance of 73% of the patients investigated while the other 27% failed to respond.

Wichtl M. (ed.). Herbal Drugs and Phytopharmaceuticals. Boca Raton, FL: CRC Press, 1994.

Yamreudeewong W, Henann NE, Fazio A, Lower DL, Cassidy TG. Drug-food interactions in clinical practice. J Fam Pract. 1995 Apr;40(4):376-84. (Review)

Hypoglycemic Herbs:
Adiantum capillus-veneris (Adiantum plant)
Allium cepa (Onion bulbs)
Allium sativum * (Garlic cloves)
Anacardium occidentale (Cashew leaves)
Arctium lappa (Burdock roots)
Argyreia cuneata (Rivea leaves)
Atriplex halimus (Salt bush leaves)
Bidens pilosa (Aceitilla plant)
Blighia sapida * (Akee Apple seeds)
Brassica oleracia (Cabbage)
Catharanthus roseus (Madagascar Periwinkle leaves)
Cecropia obtusifolia (Guarumo leaves and stem)
Coccinia grandis (Coccinia roots)
Coccinia indica (Ivy gourd)
Corchorus olitorius (Jute leaves)
Coutarea latiflora (Copalchi root bark)
Cucumis sativus (Cucumber fruit)
Cuminum cyminum (Cumin seed)
Eleutherococcus senticosus (Siberian ginseng)
Euphorbia prostrata
Ficus bengalensis * (Banyan stem bark)
Galega officinalis (Goat’s rue seeds)
Guazuma ulmifolia
Gymnema sylvestre (Gymnema leaves)
Hordeum vulgare (Barley sprouts)
Hygrophila auriculata (Barleria plant)
Lagerstroemia speciosa (Lagerstroemia leaves and ripe fruit)
Lepechinia caulescens
Lupinus albus (Lupin seeds)
Lycium barbarum (Box thorn leaves)
Lycopus virginicus (Bugleweed plant)
Momordica charantia (Bitter melon fruit)
Morus spp (Mulberry leaves)
Musa sapientum (Banana flowers and roots)
Nymphaea lotus (Lotus roots)
Ocimum sanctum (Sacred basil plant)
Olea europaea (Olive leaves)
Oplopanax horridum, also known as Fatsia horrida (Devil’s club root bark)
Opuntia spp. (Prickly pear stems and fruit)
Panax ginseng (Chinese Ginseng root)
Phaseolus vulgaris (Kidney bean, immature pods)
Polygonatum multflorum (Solomon’s seal root)
Psittacanthus calyculatus (Injerto flowers, leaves, and stem)
Rhizophora mangle
Rhus typhina (Staghorn sumach leaves)
Salpianthus arenarius (Catarinita flowers)
Sarcopoterium spinosum (Thorny burnet root bark)
Scoparia dulcis (Sweet broom plant)
Securinega virosa (Fluggea seeds)
Spinacea oleracea (Spinach leaves)
Syzygium jambolanum (Jambul seeds)
Taraxacum officinale (Dandelion plant)
Tecoma stans (Tronadora leaves)
Tinospora cordifolia (Gulancha plant)
Trigonella foenum-graecum (Fenugreek seeds)
Triticum sativum (Wheat leaves)
Turnera diffusa (Damiana leaves)
Urtica dioica (Stinging nettle plant)
Vaccinium myrtillus (Bilberry leaves)
Zea mays (Corn silk)
Note: * Indicates an herb having other side effects when taken alone in excessive doses.

(Adapted, with modifications derived from multiple source included above, from Brinker F. Herb Contraindications and Drug Interactions. pp. 104-105. Sandy, OR: Eclectic Institute, 1997.)