Method for Preventing Diet-Induced Carnitine Deficiency in Domesticated Dogs and Cats

The invention relates to the field of pet food compositions and more specifically to pet food enriched with L-Carnitine.

L-Carnitine is a quaternary amine that promotes beta-oxidation of long-chain fatty acids by facilitating their transfer across the mitochondrial membrane. L-Carnitine has also been shown to promote oxidation of branched-chain amino acids and the utilization of acetyl-coenzyme A.

In mammalian species, L-Carnitine concentration in cardiac and skeletal muscle is much higher than in serum. In these tissues fatty acids are utilized as a major source of energy. Because of L-Carnitine's central role in transporting fatty acids to the site of oxidation, adequate levels of L-Carnitine are required for normal fatty acid and energy metabolism in mammalian hearts. This is evidenced by the restoration to normal of fatty acid oxidation in muscle homogenates of certain L-Carnitine deficient patients. A relationship between deficient levels of myocardial L-Carnitine and cardiomyopathy has been observed in both hamsters and dogs. Restoration toward normal of such deficient L-Carnitine levels has been shown to result in improved myocardial function in both species.

In mammals, L-Carnitine is derived from the diet and from biosynthesis in the liver, and in some species, kidney and other tissues. Neither cardiac nor skeletal muscle is capable of synthesizing L-Carnitine, however. Thus, the L-Carnitine found in these tissues was either absorbed from the diet or biosynthesized endogenously by other tissues.

The present invention is for a method of preventing diet-induced carnitine deficiency in domesticated dogs and cats using a dietary supplement containing a prophylactic amount of L-Carnitine. The invention is useful in preventing L-Carnitine deficiencies which can lead to a multitude of conditions, including myopathic heart disease, ischemic heart disease, hyperlipidemia, ketosis, muscle weakness and premature aging.

Pets, particularly the carnivores, are at great risk for developing L-Carnitine deficiencies. As Table 1 indicates, dog and cat foods are extremely low in free L-Carnitine levels as compared with that found in raw ground beef. Most pets are maintained strictly on commercial pet food diets and are thus kept chronically deficient in L-Carnitine. Additionally, applicants' own investigations have found that renal reabsorption of L-Carnitine in dogs ranges from 40% to 95% with the average approximately 75% depending to some extent on diet. This is in marked contrast to the human which has a renal reabsorption approaching 100%. The less efficient renal reabsorption in dogs means that L-Carnitine is lost in the urine. This combined with a diet deficient in L-Carnitine results in a diet-induced carnitine deficiency.

Six apparently healthy Greyhound dogs were determined to be normal by physical examination, fecal flotation, complete blood count, serum biochemical profile, ECG, and echocardiography. They were fed a standard commercial dog food diet free choice for a one-month control period. Control plasma samples (as well as subsequent test samples) were obtained following an eight-hour fast on two consecutive days for analysis of total, free, and esterified L-Carnitine concentration. The average of the plasma L-Carnitine concentration on two consecutive days was taken for each dog and each measuring period.

Following the control period, all of the dogs were continued for two weeks on the standard commercial dog food diet supplemented with L-Carnitine. The L-Carnitine supplement was in the form of 0.5 kg per dog per day of raw frozen lean ground beef. This was equivalent to a daily supplement of 350 mg. of L-Carnitine per dog. Plasma samples were drawn on days 7 and 8 (averaged for the one-week measurement) and days 13 and 14 (averaged for the two-week measurement) for L-Carnitine analysis. Differences between the means of each test period and control were determined by the Student's t test.

The results of the study are shown in Table 2.

The data in Table 2 indicates that the plasma L-Carnitine concentration of a normal, otherwise healthy dog, previously maintained on a commercial pet food diet, is substantially deficient in carnitine as compared with the plasma carnitine levels found in other mammals. For example, in humans the mean value of plasma total carnitine is 59.3.+-.11.9 .mu.M for males and 51.5.+-.11.6 .mu.M for females. C. J. Rebouche and D. J. Paulson, Carnitine Metabolism and Function in Humans, 6 Ann. Rev. Nutr. pp. 41-66, at page 45. In rats, plasma carnitine concentration averages 56.5.+-.2.2 .mu.M. P. R. Borum, "Regulation of the Carnitine Concentration in Plasma" in Carnitine Biosynthesis, Metabolism, and Functions, 1980, Academic Press, New York, at page 119.

Further, the data of Table 2 indicates that the plasma total L-Carnitine concentration is significantly increased if the animal's diet is supplemented with L-Carnitine and that such level stabilizes in a range that is considered normal when compared with the plasma carnitine levels of other mammals. See Rebouche, supra, and Borum, supra.

It is clearly evident from the foregoing data that supplementation with a prophylactic amount of L-Carnitine of the standard commercial dog food will dramatically increase the plasma concentration of L-Carnitine in dogs. A prophylactic amount is the amount of L-Carnitine required to prevent the animal from developing a diet-induced carnitine deficiency. For a carnivore, such as a dog or cat, this is roughly equivalent to the amount of L-Carnitine the animal would ingest if its diet consisted of red meat, i.e., approximately 700 mg. of L-Carnitine per kilogram of food consumed.

Although the foregoing example details the use of raw frozen lean ground beef as a L-Carnitine source, the use of raw meat as a dietary supplement for pets is not advisable. Meat, particularly raw meat should not be fed to a pet because of the danger of transmitting parasites. In addition, meat provides excess protein which can cause and promote the progression of renal damage. Renal failure, after cancer, is the leading accidental cause of death in dogs. Lewis, et al., Small Animal Clinical Nutrition III. Chapter 2, pp 9-12, Mark Morris Associates, Topeka, Kans., 1987. The teachings of this article are incorporated herein by reference.

The preferred method of supplementation would be to administer commercially prepared L-Carnitine such as that obtained from Austin Chemical Company, Inc. 955 West Bryn Mawr Avenue, Rosemont, Ill.

These L-Carnitine supplements may be administered separately in the form of dietary supplements or they may be added at the time of manufacture of the commercial dog food as an additional ingredient in the commercial dog food. If used as a separate dietary supplement, the L-Carnitine may be combined with other valuable nutritional or prophylactic substances. Examples of this would be a combination of L-Carnitine with a vitamin and mineral preparation. Another example would be the inclusion of a prophylactic amount of L-Carnitine with an anti-heartworm medication such as diethyl-carbamazine.

The L-Carnitine supplement may also be administered as a liquid preparation. L-Carnitine is extremely soluble in water. Such a liquid preparation may be prepared by dissolving the appropriate amount of L-Carnitine in a waterbased solution. Flavoring agents or other nutritional or prophylactic substances may likewise be combined in the solution. The liquid preparation may be administered to the pet separately as a dietary supplement. It may be added to the pet's drinking water or to the animal's food. Further, the concentration of L-Carnitine in the liquid preparation may be such that it may be easily measured out and the prophylactic amount administered to the animal daily.

An alternative to administering daily a prophylactic amount of L-Carnitine to the pet, so as to avoid diet-induced carnitine deficiency, is the daily administration of a sufficient amount of gamma-butyrobetaine (GBB). GBB is the precursor of L-Carnitine in the biosynthetic pathway of the latter compound. See Nutrition Reviews, Vol. 36, No. 10, pp.305-309, 1978. The teachings of this article are incorporated herein by reference. It has been used successfully to alleviate carnitine deficiency syndromes in humans as described in U.S. Pat. No. 4,382,092 to Cavazza.

Applicants have found that administering GBB to a dog produces a concomitant use in serum L-Carnitine. See Table 3.

In the preferred embodiment, sufficient GBB will be administered orally to the pet to raise the serum L-Carnitine level to 40.0 .mu.M/liter of plasma. Administration can be accomplished in the manner described above for L-Carnitine, but the amount of GBB needed for the same amount of rise in serum L-Carnitine will be greater. In practice, between 1 to 5 grams of GBB should be administered daily, with the preferred amount being between 3-4 grams of GBB.

The use of GBB in lieu of L-Carnitine as a supplement provides a distinct economic advantage as the industrial preparation of GBB is less complicated and less expensive than the preparation of L-Carnitine. The L-Carnitine preparation requires the optical antipode resolution of the racemic mixture which is unavoidably obtained in the chemical synthesis of carnitine which necessarily increases the complexity and the expense.