Sodium

Common Names: Salt, Sodium chloride

Clinical Name: Sodium

Summary

Sodium

chemical name: Na

common form: Sodium chloride (salt).

overview of interactions:
• nutrient affected by drug: Amiloride

• nutrient affected by drug: Captopril

• nutrient affected by drug: Cisplatin

• nutrient affected by drug: Colchicine

• nutrient affected by drug: Corticosteroids including Prednisone

• nutrient affected by drug: Cyclophosphamide

• Sodium Chloride (Salt) affected by drug: Loop Diuretics and Thiazide Diuretics

• Sodium Chloride (Salt) affected by drug: Enalapril

• nutrient affected by drug: Haloperidol

• nutrient affecting drug performance: Lithium

adverse interaction: Methyldopa

• nutrient affected by drug: Penicillamine

• nutrient affected by drug: Spironolactone (Aldactone®)

• nutrient affected by drug: Sulfonylureas

• nutrient affected by drug: Triamterene

• nutrient affected by drug: Tricyclic Antidepressants

chemistry/metabolism:
• 90-98% is absorbed.
• Both sodium and potassium are actively transported into and out of the cells of the body. They are both cations. They are very water soluble and, hence, tend to dissolve easily in cooking water. Foods cooked this way tend to be much lower in nutritional value.

function:
• Acid-base balance: Both potassium and sodium are intimately involved with acid base balance and if there is an imbalance, the heart may beat irregularly.
• Water balance: Sodium is pumped out of cells while potassium is pumped into cells. Without this active pumping of sodium out of cells, swelling of the cells occurs.
• Kidney and adrenal function: Sodium is intimately involved in proper functioning adrenals.
• Muscle contraction and nerve stimulation.
• Sodium keeps other blood minerals soluble.
• Sodium is involved in hydrochloric acid production.

dietary sources:
• Sodium can be obtained from virtually all foods, especially salt, seafoods, poultry, meat, kelp, processed foods, celery, romaine lettuce, watermelon, asparagus, sea water supplement.
• Currently, the average American consumes 3-7 g per day of sodium, compared with only 2 g per day of potassium.

deficiency:
• Minimum requirements for adults: 500 mg per day.
• Replacement is usually only required after extreme perspiration.

known or potential therapeutic uses: Dehydration, glaucoma (as sodium ascorbate), eat cramps, heat strokes, and hypertension.

maintenance dose:
• Supplementation with sodium is usually not necessary.
• RDA: 0.5-2 g per day.
• Optimal daily intake: 500 mg - 2 g per day depending upon activity level.

therapeutic dose: Usually not applicable.

side effects/toxicity: No toxicities have been reported or suspected as being associated with sodium.

contraindications: Hypertension.



Interactions

nutrient affected by drug: Amiloride

• mechanism: The basic function of diuretics is to reduce the amount of water in the body. Therefore, by their very nature and intent diuretics, such as amiloride, increase the amount of sodium excreted in the urine.

• nutritional concerns: Since the reduction of sodium levels in the body is purposeful, supplementation to reduce lost sodium would be counterproductive. However, if dietary changes undertaken to restrict sodium intake are successful the dosage of diuretic medications will need to be reevaluated and possibly modified. Thus, individuals with hypertension who are using a diuretic such as amiloride while also strictly limiting their salt intake should work closely with their prescribing physician to monitor and revise their prescription based on changes in their blood pressure.
(Roe DA. 1989:146.)

nutrient affected by drug: Captopril

• mechanism: Captopril may cause hyponatremia and may also exert an anti-aldosterone effect.
(Nicholls MG, et al. Br Med J 1980 Oct 4;281(6245):909; Vitola D, et al. Arq Bras Cardiol. 1988 Dec;51(6):463-465.)

nutrient affected by drug: Cisplatin

• mechanism: Cisplatin regimens can lead to a more or less pronounced hyponatremia in 4 to 10% of cases due to salt wasting with hypomagnesemia and normokaliemia. Functional and renal failure and orthostatic hypotension can be observed.
(Peyrade F, et al. Presse Med 1997 Oct 25;26(32):1523-1525.)

• nutritional support: Cisplatin-induced hyponatremia requires specific management. Treatment is based on sodium intake which sometimes takes several months to replete stores.

nutrient affected by drug: Colchicine

• mechanism: Colchicine has been linked to impaired absorption of Sodium.
(Roe DA. 1985, 159-160.)

• nutritional support: Individuals taking colchicine would most likely benefit from taking a high-potency multivitamin/mineral supplement to compensate for these interactions.

nutrient affected by drug: Corticosteroids including Prednisone

• mechanism: Steroidal anti-inflammatory drugs typically cause increased sodium retention. The mineralocorticoid action of cortisol can cause a drop in serum potassium and an increase in serum sodium concentration which might lead to water retention, weight gain, and increased risk of hypertension. Individuals using corticosteroids should consult with their prescribing physician and/or a nutritionally trained healthcare professional about the potential need to restrict dietary salt intake.

nutrient affected by drug: Cyclophosphamide

• mechanism: The antidiuretic effect of cyclophosphamide may induce dilutional hyponatremia and water intoxification, especially when hospitalized patients are under a concomitant overhydration protocol.
(Steele TH, et al. J Pharmacol Exp Ther. 1973 May;185(2):245-253; Bode U, et al. Med Pediatr Oncol. 1980;8(3):295-303; Spital A, Ristow S. J Rheumatol 1997 Dec;24(12):2473-2475; Chintanadilok J, et al. Geriatr Nephrol Urol. 1998;8(3):161-165; Berghmans T. Support Care Cancer. 1996 Sep;4(5):341-350; Webberley MJ, et al. Postgrad Med J. 1989 Dec;65(770):950-952.)

Sodium Chloride (Salt) affected by drug: Loop Diuretics and Thiazide Diuretics

• mechanism: The intended function of loop and thiazide diuretics is to interfere with renal reabsorption of both sodium and chloride, with sodium excretion in particular being the fundamental purpose of the drug. The increased excretion of sodium leads to an increased excretion of water from the body and thereby cause a lowering of blood pressure and reduced load on the heart.

• nutritional concerns: Since decreased sodium levels are intentional, individuals who have been prescribed diuretics should not increase their salt intake without explicit directions from their prescribing physician to this effect. The corresponding drug-induced depletion of chloride is typically mild and usually not significant for individuals with normal liver and kidney function.

Sodium Chloride (Salt) affected by drug: Enalapril

• mechanism: Hypertension in obese patients is associated with hyperinsulinemia and salt sensitivity. However, the very low salt diets often prescribed for individuals with high blood pressure may exacerbate hyperinsulinemia, perhaps by activating the renin-angiotensin system.

• nutritional synergy: Preliminary research indicates that under the influence of enalapril, severe salt restriction decreases blood pressure while raising insulin levels in overweight individuals with mild hypertension. Individuals taking enalapril should discuss dietary changes, especially involving restricting salt intake, with their physician and/or a nutritionally-oriented healthcare provider.
(Egan BM, et al. Am J Cardiol 1993 Jul 1;72(1):53-57.)

nutrient affected by drug: Haloperidol

• mechanism: The use of haloperidol is associated with hyponatremia, i.e., low blood levels of sodium. The dopamine system seems to be relatively more important in promoting excretion of sodium at the lower (physiological) range of hypervolemia whereas in the high range other factors have a greater impact.
(Cuche JL, et al. Nephrologie. 1983;4(3):103-105; Hansell P, et al. Acta Physiol Scand. 1987 Jul;130(3):401-407; Hansell P, et al. Kidney Int. 1991 Feb;39(2):253-258.)

• nutritional concerns: The clinical significance of changes in sodium levels due to haloperidol remains unclear. Individuals concerned about this aspect of haloperidol intoxications side effects should consult their prescribing physician and/or pharmacist. Serum sodium levels are commonly measured as part of standard lab tests.

nutrient affecting drug performance: Lithium

• 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.

adverse interaction: Methyldopa

• mechanism: Methyldopa is intended to reduce blood pressure. Consequently, limiting dietary sodium (salt) intake is advisable since high levels can contribute to fluid retention and thereby interfere with the intended action of methyldopa in lowering blood pressure.

• nutritional support: The simplest way to avoid this counterproductive effect is to reduce the consumption of table salt and heavily salted foods while using methyldopa for the treatment of hypertension.

nutrient affected by drug: Penicillamine

• nutritional concerns: Some researchers have reported an association between penicillamine therapy and sodium depletion. The frequency and clinical significance of this association remains unclear.

nutrient affected by drug: Spironolactone (Aldactone®)

• mechanism: The basic function of diuretics is to reduce the amount of water in the body. Therefore, by their very nature and intent diurectics, such as spironolactone, increase the amount of sodium excreted in the urine.

• nutritional concerns: Since the reduction of sodium levels in the body is purposeful, supplementation to reduce lost sodium would be counterproductive. However, if dietary changes undertaken to restrict sodium intake are successful the dosage of diuretic medications will need to be reevaluated and possibly modified. Thus, individuals with hypertension who are using a diuretic such as spironolactone while also strictly limiting their salt intake should work closely with their prescribing physician to monitor and revise their prescription based on changes in their blood pressure.
(Roe DA. 1989: 146.)

nutrient affected by drug: Sulfonylureas

• mechanism: Hyponatremia has been observed in 6-10% of diabetics treated with chlorpropamide. The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) has occasionally occurred with chlorpropamide. SIADH is characterized by excessive water retention and hyponatremia, low serum osmolality and high urine osmolality. These adverse effects have been reported most commonly in the elderly and patients with congestive heart failure or with hepatic cirrhosis, or with individuals taking diuretics.
(Berger W. Horm Metab Res Suppl 1985;15:111-115.)

nutrient affected by drug: Triamterene

• mechanism: The basic function of diuretics is to reduce the amount of water in the body. Therefore, by their very nature and intent diuretics, such as triamterene, increase the amount of sodium excreted in the urine.

• nutritional concerns: Since the reduction of sodium levels in the body is purposeful, supplementation to reduce lost sodium would be counterproductive. However, if dietary changes undertaken to restrict sodium intake are successful the dosage of diuretic medications will need to be reevaluated and possibly modified. Thus, individuals with hypertension who are using a diuretic such as triamterene while also strictly limiting their salt intake should work closely with their prescribing physician to monitor and revise their prescription based on changes in their blood pressure.
(Roe DA. 1989: 146.)

nutrient affected by drug: Tricyclic Antidepressants

• research: Amitriptyline may cause dilutional hyponatremia, excessively low levels of sodium in the blood, as a result of inappropriate secretion of antidiuretic hormone. Manifestations are those of water intoxication, eg, confusion, fatigue, nausea, headache, and neurologic signs.
(Luzecky MH, et al. South Med J 1974 Apr;67(4):495-497; Beckstrom D, et al. JAMA 1979 Jan 12;241(2):133.)

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

Beckstrom D, Reding R, Cerletty J. Syndrome of inappropriate antidiuretic hormone secretion associated with amitriptyline administration. JAMA 1979 Jan 12;241(2):133. (Letter)

Berger W. Incidence of severe side effects during therapy with sulfonylureas and biguanides. Horm Metab Res Suppl 1985;15:111-115.
The most important side-effect of sulfonylureas is hypoglycaemia. According to surveys in Switzerland and in Sweden it occurs at a frequency of about 2 cases per 10,000 treatment years. Mortality is high, about 10%. The syndrome of inappropriate ADH-secretion has been observed almost exclusively during treatment with chlorpropamide. Asymptomatic cases of SIADH-syndrome are quite frequent, hyponatraemia has been observed in 6-10% of diabetics treated with chlorpropamide. The most dangerous side-effect of biguanides is lactic acidosis. It occurs significantly more frequent during treatment with phenformin compared to metformin. Metformin has been reported to lead to lactic acidosis in 0.4 cases per 10,000 treatment years; mortality is about 30%. Mortality of phenformin-associated lactic acidosis is even higher, 70%. Both biguanides, phenformin and metformin, cause relatively frequently vitamin B12-malabsorption (in about 1/3 of the cases). However, symptomatic vitamin B12-deficiency is extremely rare.

Berghmans T. Hyponatremia related to medical anticancer treatment. Support Care Cancer. 1996 Sep;4(5):341-50. (Review)

Bode U, Seif SM, Levine AS. Studies on the antidiuretic effect of cyclophosphamide: vasopressin release and sodium excretion. Med Pediatr Oncol. 1980;8(3):295-303.

Chintanadilok J, Kallas H, Lowenthal DT. Lung cancer and drug-induced severe hyponatremia. Geriatr Nephrol Urol. 1998;8(3):161-165.

Cuche JL, Prinseau J, Baglin A, Guedon J. [Natriuretic effect of haloperidol in dogs]. Nephrologie. 1983;4(3):103-105. [Article in French]
Abstract: A 0.5 microM/kg/min infusion of haloperidol in the renal artery of 20 sodium-loaded dogs undergoing water diuresis is showed to induce the following net effects: a statistically significant reduction of both clearance of PAH (-18.1 +/- 6.6 ml/min), and glomerular filtration rate (-4.3 +/- 1.5 ml/min), an increase of both fractional excretion of sodium (+ 6.8 +/- 1.1%) and potassium (+ 55.1 +/- 5.5%), a decrease of fractional excretion of phosphate (-5.3 +/- 1.5%), and a lack of change of free water clearance (infused minus controlateral kidney difference).

Egan BM, Stepniakowski K. Effects of enalapril on the hyperinsulinemic response to severe salt restriction in obese young men with mild systemic hypertension. Am J Cardiol 1993 Jul 1;72(1):53-57.
Abstract: Hypertension in obese patients is associated with hyperinsulinemia and salt sensitivity. Very low salt diets may exacerbate hyperinsulinemia, perhaps by activating the renin-angiotensin system. Therefore, the effects of a low salt diet alone and with enalapril on blood pressure and the insulin response to an oral glucose tolerance test were studied in 9 obese (body mass index 35 +/- 2 kg/m2) men with mild hypertension. Measurements were first obtained after a 2-week high-salt (20 mEq/day sodium diet+eleven 1 g salt tablets per day) baseline period. The same measurements were repeated after 2 weeks on a low salt diet (20 mEq/day) and after 2 weeks on low salt diet with enalapril in random sequence. The insulin area under the curve increased from 12.8 +/- 3.0 mU-min/dl during high salt to 16.6 +/- 3.2 mU-min/dl (p < 0.001). Plasma renin activity also increased with salt restriction from 1.4 +/- 0.2 to 3.0 +/- 0.5 ng/ml/hour, p = 0.01. With addition of enalapril to the low sodium chloride diet, the insulin area under the curve (14.5 +/- 2.6 mU-min/dl) was not significantly different from that during the high sodium chloride phase. Mean blood pressure in the laboratory was 105 +/- 1 mm Hg with high salt versus 99 +/- 1 mm Hg with low salt, p < 0.05. Addition of enalapril to the low-salt diet reduced mean blood pressure to 87 +/- 1 mm Hg (p < 0.01 vs low salt), largely by reducing total systemic resistance (p < 0.05). Salt restriction decreases laboratory BP while raising insulin levels in obese men with mild hypertension.

Hansell P, Fasching A, Sjoquist M, Anden NE, Ulfendahl HR. The dopamine receptor antagonist haloperidol blocks natriuretic but not hypotensive effects of the atrial natriuretic factor. Acta Physiol Scand. 1987 Jul;130(3):401-407.

Hansell P, Fasching A. The effect of dopamine receptor blockade on natriuresis is dependent on the degree of hypervolemia. Kidney Int. 1991 Feb;39(2):253-258.
Abstract: A number of different physiological factors and systems have been suggested to be responsible for the natriuretic effect following acute isotonic volume expansion (VE). The variation in suggestions may depend on the prevailing status of the systems governing fluid and electrolyte balance before VE, on the expansion medium and on the rate and degree of VE. A study was performed to determine whether the previously documented attenuating effect of dopamine receptor blockade on natriuresis induced by VE is dependent on the degree of hypervolemia. Anesthetized rats were pretreated with the dopamine receptor blockers haloperidol (1 mg.kg-1 body weight, i.p.), SCH 23390 (30 micrograms.hr-1.kg-1 i.v.) or vehicle and then subjected to VE at 2, 5 or 10% of body weight per hour. VE at 2, 5 and 10% increased sodium excretion in vehicle-pretreated animals 6-, 29- and 130-fold, respectively. In the haloperidol-pretreated animals the natriuretic response (accumulated sodium excretion) to VE was attenuated by 67% (P less than 0.05), 46% (P less than 0.05) and 22% (NS) at the three degrees of expansion, respectively. The corresponding attenuation in SCH 23390-treated animals were 60% (P less than 0.05), 56% (P less than 0.05) and 19% (NS), respectively. The gradual decrease in attenuation indicates that at varying degrees of hypervolemia, different physiological systems contribute differently to the renal natriuretic response. The dopamine system seems to be relatively more important in promoting natriuresis at the lower (physiological) range of hypervolemia whereas in the high range other factors have a greater impact.

Holt GA. Food and Drug Interactions. Chicago: Precept Press, 1998.

Luzecky MH, Burman KD, Schultz ER. The syndrome of inappropriate secretion of antidiuretic hormone associated with amitriptyline administration. South Med J 1974 Apr;67(4):495-497.

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Nicholls MG, Espiner EA, Ikram H, Maslowski AH. Hyponatraemia in congestive heart failure during treatment with captopril. Br Med J 1980 Oct 4;281(6245):909.

Peyrade F, Taillan B, Lebrun C, Bendini JC, Passerron C, Dujardin P. [Hyponatremia during treatment with cisplatin]. Presse Med 1997 Oct 25;26(32):1523-1525. [Article in French]
Abstract: BACKGROUND: Cisplatin is one of the most widely used agents in cancer treatment. Cisplatin regimens can lead to a more or less pronounced hyponatremia in 4 to 10% of cases due to salt wasting with hypomagnesemia and normokaliemia. Functional and renal failure and orthostatic hypotension can be observed. CASE REPORT: A 54-year-old woman with brain metastases of a non-small-cell lung cancer was given a chemotherapy regimen containing cisplatin. Hyponatremia with confusion occurred after each cisplatin perfusion. The diagnosis retained was cisplatin-induced salt wasting. The patient was given salt prolonged supplementation and carboplatin was substituted for cisplatin in the chemotherapy regimen. DISCUSSION: Hyponatremia frequently occurs in cancer patients. Cisplatin-induced hyponatremia requires specific management. Treatment is based on sodium intake which sometimes takes several months to replete stores. Carboplatin can be used instead of cisplatin in case of major hyponatremia.

Pronsky, Zaneta. Powers and Moore's Food-Medications Interactions. Ninth Edition. Food-Medication Interactions. Pottstown, PA, 1991.

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Soszynski P, Slowinska-Srzednicka J, Kasperlik-Zaluska A, Zgliczynski S. Endogenous natriuretic factors: atrial natriuretic hormone and digitalis-like substance in Cushing's syndrome. J Endocrinol 1991 Jun;129(3):453-458.
Abstract: In order to investigate the effect of chronic hypercortisolaemia on endogenous natriuretic factors (atrial natriuretic hormone (ANH) and the Na+/K+ pump inhibitor) digitalis-like substance (DLS), and their relation to hypertension, 28 patients with pituitary- or adrenal-dependent Cushing's syndrome and six patients on high-dose prednisone treatment were studied. Plasma ANH levels were increased in patients with Cushing's syndrome (36.0 +/- 1.4 (S.E.M.) ng/l) compared with those in healthy controls (28.6 +/- 1.3 ng/l, P less than 0.01). In prednisone-treated patients, ANH levels (43.8 +/- 4.5 ng/l) were higher than those in patients with Cushing's syndrome and in controls (P less than 0.05 and P less than 0.01 respectively). DLS measured by radioimmunoassay and binding of [3H]ouabain to erythrocytes was not altered in patients with hypercortisolaemia. Slightly decreased DLS activity in the erythrocyte 86Rb uptake inhibition assay was found in patients with Cushing's syndrome (52.9 +/- 2.7%) compared with that in controls (60.9 +/- 1.8%, P less than 0.02). With the exception of cortisol (r = 0.52, P less than 0.01), none of the other factors determined correlated with the mean arterial pressure in patients with Cushing's syndrome. Thus, a chronic excess of endogenous and exogenous glucocorticoids increases plasma levels of ANH, but does not substantially influence DLS activity or plasma levels. Neither natriuretic factor is directly related to hypertension in Cushing's syndrome.

Spital A, Ristow S. Cyclophosphamide induced water intoxication in a woman with Sjogren's syndrome. J Rheumatol 1997 Dec;24(12):2473-2475.
Abstract: Water intoxication is a well described complication of high dose intravenous (i.v.) cyclophosphamide therapy combined with forced hydration. Less well known is that water intoxication can develop even after low dose iv cyclophosphamide. To draw attention to this potentially life threatening complication, we describe a woman who developed acute water intoxication after treatment with low dose iv cyclophosphamide for a sensory neuropathy secondary to Sjogren's syndrome. Rheumatologists should be aware of this serious adverse effect of iv cyclophosphamide because this drug is being used increasingly for treatment of a variety of rheumatological diseases. The pathogenesis, clinical characteristics, treatment, and methods for prevention of cyclophosphamide induced water intoxication are discussed.

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Vitola D, Bittar AE, Junges F, dos Santos AA, Rodrigues R. [Hyponatremia induced by captopril in patients with congestive cardiac insufficiency. A report of 2 cases]. Arq Bras Cardiol. 1988 Dec;51(6):463-465. [Article in Portugese]

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