Milk-containing Foods

Common Names: Dairy; Lactose

Clinical Name: Milk-containing Foods

Summary

Milk-containing Foods

overview of interactions:
• diet affecting drug performance: Tetracyclines

• food constituent affected by drug: Colchicine

Interactions

diet affecting drug performance: Tetracyclines

• mechanism: Absorption of tetracycline class drugs takes place mainly in the stomach and upper small intestine. Food and dairy products containing high concentrations of calcium may decrease the absorption of tetracyclines due to chelate formation in the gut. This binding of the drug to the mineral may also lead to growth retardation and pigmented teeth. Furthermore, tetracycline increases urinary calcium excretion. Thus, with prolonged use, tetracycline can adversely effect bone formation and contribute to calcium depletion.

The interaction between tetracycline and calcium-rich foods such as milk products exerts adverse effects on both and teeth that are well documented and widely recognized. Tetracyclines form a stable calcium complex in any bone-forming tissue. Unwanted pigmentation and other problems with tooth development due to tetracycline are well known to dentists and the general public. The tetracyclines also tend to localize in tumors, necrotic or ischemic tissue, liver and spleen and form tetracycline-calcium orthophosphate complexes at sites of new bone formation.

Tetracyclines are potent inhibitors of osteoclast function (i.e., anti-resorptive). Vernillo and Rifkin described the processes by which tetracyclines can affect several parameters of osteoclast function and consequently inhibit bone resorption: (1) altering intracellular calcium concentration and interacting with the putative calcium receptor; (2) decreasing ruffled border area; (3) diminishing acid production; (4) diminishing the secretion of lysosomal cysteine proteinases (cathepsins); (5) inducing cell retraction by affecting podosomes; (6) inhibiting osteoclast gelatinase activity; (7) selectively inhibiting osteoclast ontogeny or development; and (8) inducing apoptosis or programmed cell death of osteoclasts.
(Vernillo AT, Rifkin BR. Adv Dent Res 1998 Nov;12(2):56-62; Roe DA. 1989:87.)

• research: This effect on bone formation carries a significantly greater risk when growth and bone formation is most active, such as with infants and children. A decrease in the fibula growth rate has been observed in premature infants receiving oral tetracycline in doses of 25 mg/kg every 6 hours. This reaction was shown to be reversible when the drug was discontinued.
(Jung H, et al. Biopharm Drug Dispos 1997 Jul;18(5):459-463; Roe DA. 1989:87; Drug Evaluation Subscription. Winter 1993; Hammarstrom L. Lakartidningen 1968 Jun 4;65:Suppl 2:89-96.)

• nutritional concerns: Calcium in the form of milk products, as well as antacids and supplements, should be avoided while using tetracycline. If, after consultation with the prescribing physician, continued use of calcium supplements is deemed necessary, the calcium supplement should be taken several hours apart from ingestion of the drug.

food constituent affected by drug: Colchicine

• mechanism: Colchicine has been linked to impaired absorption of lactose. In studies of patients with familial Mediterranean fever (FMF) Fradkin et al found that colchicine induces significant lactose malabsorption in FMF patients and concluded that this interaction was at least partially responsible for the gastrointestinal side effects of the drug.
(Roe DA. 1985, 159-160; Werbach, MR. 1997, 223-224; Race TF, et al. Am J Med Sci 1970 Jan;259(1):32-41; Fradkin A, et al. Isr J Med Sci. 1995 Oct;31(10):616-620.)

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

Cook HJ, Mundo CR, Fonseca L, Gasque L, Moreno-Esparza R. Influence of the diet on bioavailability of tetracycline. Biopharm Drug Dispos 1993 Aug;14(6):549-553.

Fradkin A, Yahav J, Zemer D, Jonas A.  Colchicine-induced lactose malabsorption in patients with familial Mediterranean fever. Isr J Med Sci. 1995 Oct;31(10):616-620.
Abstract: Abdominal pain and diarrhea are frequent side effects of chronic colchicine therapy. Drug-induced lactose deficiency has been demonstrated in the experimental animal. Lactose malabsorption was assessed by the lactose breath test in 23 patients with familial Mediterranean fever (FMF) receiving colchicine for 0.25-15 years (mean 3.16). Twenty FMF patients not receiving colchicine and 38 non-FMF lactose malabsorbers served as controls. Patients receiving colchicine had a significantly higher percentage of lactose malabsorption (20/23, 87%) versus nontreated FMF patients (13/20, 65%; P < 0.05). Lactose intolerance was also more prevalent in colchicine-treated patients (17/23, 74%) versus nontreated FMF (5/20, 25%; P < 0.0005) and control lactose malabsorbers (16/38, 42%; P < 0.01). Of the 12 patients investigated before and 3 months after colchicine administration, 7 showed induction or aggravation of lactose malabsorption. The lactose-free diet resulted in partial improvement of symptoms. Colchicine induces significant lactose malabsorption in FMF patients and this is partially responsible for the gastrointestinal side effects of the drug.

Hammarstrom L. [Side-effects on bone and teeth of the tetracyclines]. Lakartidningen 1968 Jun 4;65:Suppl 2:89-96. [Article in Swedish]

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

Jung H, Peregrina AA, Rodriguez JM, Moreno-Esparza R. The influence of coffee with milk and tea with milk on the bioavailability of tetracycline. Biopharm Drug Dispos 1997 Jul;18(5):459-463.
Abstract: The effect of milk added to coffee or black tea on the bioavailability of tetracycline was evaluated in 12 healthy volunteers according to a crossover design. Results showed that even a small volume of milk containing extremely small amounts of calcium severely impair the absorption of the drug, so that the presence of this metal ion should be carefully controlled in order to avoid decreasing the available tetracycline.

Leyden JJ. Absorption of minocycline hydrochloride and tetracycline hydrochloride. Effect of food, milk, and iron. J Am Acad Dermatol 1985 Feb;12(2 Pt 1):308-312.
Abstract: Serum concentrations of tetracycline hydrochloride and minocycline hydrochloride were compared when administered with water, milk, a meal, and 300 mg ferrous sulfate in two groups of eight volunteers. Absorption of both antibiotics was significantly decreased by administration with iron (77% inhibition with minocycline and 81% with tetracycline), milk (27% inhibition with minocycline, 65% with tetracycline), and food (13% inhibition with minocycline and 46% with tetracycline). The inhibitory effect on absorption with food and milk was significantly greater for tetracycline than for minocycline.

Race TF, Paes IC, Faloon WW. Intestinal malabsorption induced by oral colchicine. Comparison with neomycin and cathartic agents. Am J Med Sci 1970 Jan;259(1):32-41.

Robinson C, Weigly E. Basic Nutrition and Diet Therapy. New York: MacMillan, 1984.

Roe DA. Diet and Drug Interactions. New York: Van Nostrand Reinhold, 1989.

Roe DA. Drug-induced Nutritional Deficiencies. 2nd ed. Westport, CT: Avi Publishing, 1985.

Roe DA. Risk factors in drug-induced nutritional deficiencies. In: Roe DA, Campbell T, eds. Drugs and Nutrients: The Interactive Effects. New York: Marcel Decker, 1984: 505-523.

Threlkeld DS, ed. Anti-Infectives, Tetracyclines. In: Facts and Comparisons Drug Information. St. Louis, MO: Facts and Comparisons, Dec 1989.

Trovato A, Nuhlicek DN, Midtling JE. Drug-nutrient interactions. Am Fam Physician 1991 Nov;44(5):1651-1658.(Review)

Vernillo AT, Rifkin BR. Effects of tetracyclines on bone metabolism. Adv Dent Res 1998 Nov;12(2):56-62.
Abstract: The anti-resorptive properties of tetracyclines (TCs) and their non-antimicrobial, chemically modified analogues (CMTs) have enormous therapeutic potential in medicine and dentistry. Osseous destructive diseases associated with excessive mammalian collagenase (matrix metalloproteinase) activity and collagen breakdown include malignancy, arthritis, and periodontitis. However, apart from the significant antimatrix metalloproteinase effects of TCs, TCs/CMTs are also potent inhibitors of osteoclast function (i.e., anti-resorptive). Thus, TCs can affect several parameters of osteoclast function and consequently inhibit bone resorption by (1) altering intracellular calcium concentration and interacting with the putative calcium receptor; (2) decreasing ruffled border area; (3) diminishing acid production; (4) diminishing the secretion of lysosomal cysteine proteinases (cathepsins); (5) inducing cell retraction by affecting podosomes; (6) inhibiting osteoclast gelatinase activity; (7) selectively inhibiting osteoclast ontogeny or development; and (8) inducing apoptosis or programmed cell death of osteoclasts. TCs/CMTs, as anti-resorptive drugs, may act similarly to bisphosphonates and primarily affect osteoclast function.

Wallace SL. Mechanism of action of colchicine. Arthritis Rheum. 1965 Oct;8(5):744-748.

Werbach MR. Foundations of Nutritional Medicine. Tarzana, CA: Third Line Press, 1997. (Review)