Carnimag is a patented compound whose constituents are L-carnitine base, magnesium chloride, magnesium oxide and crystallised water. It is a nutritional supplement that facilitates the transport of metabolic energy thus protecting against mental and physical stress to the brain and body as well as preventing and treating magnesium deficiency. Some research conducted with these ingredients is listed below.

L-carnitine 

About 60 to 75% of L-carnitine from food is absorbed. The percentage absorbed from supplements appears to be lower. In one study only 20% of a 2-gram dose of L-carnitine was found to be absorbed following ingestion. Most of an ingested dose of L-carnitine is absorbed by the small intestine, apparently by facilitative diffusion and active transport.

Two types of L-carnitine deficiency states exist, namely primary systemic carnitine deficiency (SCD) and secondary carnitine deficiency syndromes. SCD is an autosomal recessive disorder characterized by progressive cardiomyopathy, skeletal myopathy, hypoglycaemia and hyperammonemia. SCD appears to be due, in part, to loss of function of the transporter protein called OCT N2, which helps carry L-carnitine into cells.

Secondary L-carnitine deficiency disorders include a large number of entities. Some of these are genetic defects of metabolism such as methylmalonic aciduria, cytochrome C oxidase deficiency, fatty acyl-coenzyme A dehydrogenase deficiency, including long-chain and medium-chain deficiency, isovaleric acidemia, glutaric aciduria and propionic acidemia.

Approximately 95% of filtered L-carnitine is reabsorbed in healthy humans. Hypothyroidism decreases the urinary excretion of L-carnitine, while hyperthyroidism increases it.
Following absorption from the intestine, about 25% of L-carnitine may be acylated in the intestinal mucosa. Orally administered L-carnitine and its acylated metabolite are distributed to most tissues of the body. Uptake of L-carnitine into cells is thought to occur by facilitative diffusion and, in some cases, by active transport. Most of the body's stores of L-carnitine are found in cardiac and skeletal muscle.

Therapeutic dosage is 1 to 3 grams per day.

Carnitine deficiency

Two types of L-carnitine deficiency states exist:

Primary systemic carnitine deficiency (SCD) and secondary carnitine deficiency syndromes. SCD is an autosomal recessive disorder characterized by progressive cardiomyopathy, skeletal myopathy, hypoglycaemia and hyperammonemia. SCD appears to be due, in part, to loss of function of the transporter protein called OCT N2, which helps carry L-carnitine into cells. Patients with SCD have low L-carnitine levels in liver and skeletal muscle and variable concentrations of L-carnitine in the serum. Treatment with large doses of L-carnitine either orally or intravenously is sometimes beneficial in this rare genetic disorder.

Secondary L-carnitine deficiency disorders include a large number of entities. Some of these are genetic defects of metabolism such as methylmalonic aciduria, cytochrome C oxidase deficiency, fatty acyl-coenzyme A dehydrogenase deficiency, including long-chain and medium-chain deficiency, isovaleric acidemia, glutaric aciduria and propionic acidemia. There is some preliminary evidence that secondary L-carnitine deficiency may also be associated with ageing.

Carnitine deficiency has been linked to certain fatal diseases such as heart failure and Hypoglycemic hypoketotic encephalopathy.

Further reading:

Bohles H, Richter K, Wagner-Thiesson E, Schafer H. Decreased serum carnitine in valproate induced Reye syndrome. Eur J Pediatr. 1982; 139:185-186.

Bohmer T, Rynding A, Solberg HE. Carnitine levels in human serum in health and disease. Clin Chim Acta. 1974; 57:55-61.

Borum PR. Carnitine. Ann Rev Nutr. 1983; 3:233-259.

Brevetti G, Diehm C, Lambert D. European multicenter study on propionyl-L-carnitine in intermittent claudication. J Am Coll Cardiol. 1999; 35:1618-1624.

Brevetti G, Chiarello M, Ferulano G, et al. Increases in walking distance in patients with peripheral vascular disease: a double-blind, cross-over study. Circul. 1988; 77:767-773.

Brooks H, Goldberg L, Holland R, et al. Carnitine-induced effects on cardiac and peripheral hemodynamics. J Clin Pharmacol. 1977; 17:561-578.

Christiansen R, Bremer J. Active transport of butyrobetaine and carnitine into isolated liver cells. Biochem Biophys Acta. 1977; 448:562-577.

de Simone C, Famularo G, Tzantzoglov S, et al. Carnitine depletion in peripheral blood mononuclear cells from patients with AIDS: effect of L-carnitine. AIDS. 1994; 8:655-660.

Famularo G, Moretti S, Marcellini S, et al. Acetyl-carnitine deficiency in AIDS patients with neurotoxicity on treatment with antiretroviral nucleoside analogues. AIDS. 1997; 11:185-190.

Lindstedt S, Lindstedt G. Distribution and excretion of carnitine 14CO2 in the rat. Acta Chim Scand. 1961; 15:701-702.

Maebashi M, Kawamura N, Sato M, et al. Lipid-lowering effects of carnitine in patients with type-IV hypolipoproteinaemia. Lancet. 1978; 2:805-807.

Marzo A, Arrigoni Martelli E, Mancinelli A, et al. Protein binding of L-carnitine family components. Eur J Drug Met Pharmacokin Special Issue III. 1992; 364-368.
Nezu J, Tamai I, Oku A, et al. Primary systemic carnitine deficiency is caused by mutations in a gene encoding sodium ion-dependent carnitine transporter. Nat Gen. 1999; 21:91-94.

Opie LH. Role of carnitine in fatty acid metabolism of normal and ischemic myocardium. Am Heart J. 1979; 97:375-388.

Levocarnitine. Physicians' Desk Reference. 54 ed. Montvale, NJ; Medical Economics Company. 2000:2957-2959.

Pola P, Savi L Grilli M, et al. Carnitine in the therapy of dyslipidemic patients. Curr Therapeu Res. 1980; 27:208-216.

Prockup LD, Engel WK, Shug AL. Nearly fatal muscle carnitine deficiency with full recovery after replacement therapy. Neurol. 1983; 33:1629-1631.

Rebouche CJ. Carnitine. In: Shils ME, Olson JA, Shike M, Ross AC, eds. Modern Nutrition in Health and Disease. 9th ed. Baltimore, MD: Williams & Wilkins; 1999:505-512.

Rebouche CJ. Carnitine function and requirements during the life cycle. FASEB J. 1992; 6:3379-3386.

Rebouche CJ, Engel AG. Carnitine metabolism and deficiency syndromes. Mayo Clin Proc. 1983; 58:533-540.

Rebouche CJ, Paulson DJ. Carnitine metabolism and function in humans. Ann Rev Nutr. 1986; 6:41-68.

Rossi CS, Siliprandi N. Effects of carnitine on serum HDL-cholesterol: report of two cases. Johns Hopkins Medical J. 1982; 150:51-54.

Sachan DS, Rhew TH, Ruark RA. Ameliorating effects of carnitine on alcohol-induced fatty liver. Am J Clin Nutr. 1984; 39:738-744.

Triggs WJ, Bohan TP, Shen-Nan L, Wilmore J. Valproate-induced coma with ketosis and carnitine insufficiency. Arch Neurol. 1990; 47:1131-1133.

Vacha GM, Giorcelli G, Siliprandi N, Corsi G. Favorable effects of L-carnitine treatment on hypertriglyceridemia in hemodialysis patients: decisive role of low levels of high-density lipoprotein-cholesterol. Am J Clin Nutr. 1983; 38:532-540.

Magnesium

Magnesium plays a role in many crucial enzyme systems, especially those involving ATP metabolism. It is a mineral needed by every cell of the body and is needed for more than 300 biochemical reactions in the body. It helps to maintain normal muscle and nerve function, keeps heart rhythm steady, and bones strong. It is also involved in energy metabolism and protein synthesis

Healthy adults who eat a varied diet do not generally need to take a magnesium supplement but deficiency is usually indicated when a specific health problem or condition causes an excessive loss of magnesium or limits magnesium absorption (27, 30, 31, 33-38).
Loop and thiazide diuretics, such as Lasix, Bumex, Edecrin, and Hydrochlorothiazide, can increase loss of magnesium in urine (31). Medicines such as Cisplatin (32), which is widely used to treat cancer, and the antibiotics Gentamicin, Amphotericin, and Cyclosporin also cause the kidneys to excrete (lose) more magnesium in urine (30).

Poorly controlled diabetes increases loss of magnesium in urine and may increase an individual's need for magnesium. A medical doctor would determine the need for extra magnesium in this situation. Routine supplementation with magnesium is not indicated for individuals with well-controlled diabetes (36, 37, 39, 40).

People who abuse alcohol are at high risk for magnesium deficiency because alcohol increases urinary excretion of magnesium. Low blood levels of magnesium occur in 30 percent to 60 percent of alcoholics, and in nearly 90 percent of patients experiencing alcohol withdrawal (34). In addition, alcoholics who substitute alcohol for food will usually have lower magnesium intakes (33, 34). Medical doctors routinely evaluate the need for extra magnesium in this population.

The loss of magnesium through diarrhoea and fat malabsorption usually occurs after intestinal surgery or infection, but it can occur with chronic malabsorptive problems such as Crohn's disease, gluten sensitive enteropathy, and regional enteritis (35).

Individuals with chronically low blood levels of potassium and calcium may have an underlying problem with magnesium deficiency. Adding magnesium supplements to their diets may make potassium and calcium supplementation more effective for them (27, 38). Doctors routinely evaluate magnesium status when potassium and calcium levels are abnormal, and prescribe a magnesium supplement when indicated.

Evidence suggests that magnesium may play an important role in regulating blood pressure (29). Diets that provide plenty of fruits and vegetables, which are good sources of potassium and magnesium, are consistently associated with lower blood pressure (41-43). The DASH study (Dietary Approaches to Stop Hypertension) suggested that high blood pressure could be significantly lowered by a diet high in magnesium, potassium, and calcium, and low in sodium and fat (44-46). In another study, the effect of various nutritional factors on incidence of high blood pressure was examined in over 30,000 U.S. male health professionals. After four years it was found that a greater magnesium intake was significantly associated with a lower risk of hypertension (47). The evidence is strong enough that the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure recommends maintaining an adequate magnesium intake as a positive lifestyle modification for preventing and managing high blood pressure (48-50).

Magnesium deficiency can cause metabolic changes that may contribute to heart attacks and strokes (51-53). There is also evidence that low body stores of magnesium increase the risk of abnormal heart rhythms (29) Population surveys have associated higher blood levels of magnesium with lower risk of coronary heart disease (54-55). In addition, dietary surveys have suggested that a higher magnesium intake is associated with a lower risk of stroke (56).

Magnesium deficiency may be a risk factor for postmenopausal osteoporosis (29). This may be due to the fact that magnesium deficiency alters calcium metabolism and the hormone that regulates calcium (35). Several studies have suggested that magnesium supplementation may improve bone mineral density (29).

Concerning diabetes, magnesium is important to carbohydrate metabolism. It may influence the release and activity of insulin, the hormone that helps control blood glucose levels (37). Elevated blood glucose levels increase the loss of magnesium in the urine, which in turn lowers blood levels of magnesium [(36). This explains why low blood levels of magnesium (hypomagnesemia) are seen in poorly controlled type 1 and type 2 diabetes.
In 1992, the American Diabetes Association issued a consensus statement that concluded: “Adequate dietary magnesium intake can generally be achieved by a nutritionally balanced meal plan as recommended by the American Diabetes Association.” It recommended that “... only diabetic patients at high risk of hypomagnesemia should have total serum (blood) magnesium assessed, and such levels should be repleted (replaced) only if hypomagnesemia can be demonstrated” (40).

Medication that may have beneficial or harmful interactions with L-carnitine:

• Allupurinol (Zyloprim) - might improve muscle strength in people with Duchenne muscular dystrophy. (Digiesi V, etal 1989)
• Anticonvulsants – Carbemazepine (Tegretol®); Ethosuxamide (Zarontin®);  Phenytoin (Epinutan®); Phenobarbital (Gardenal®); Lamotrigine (Lamictin®); Toprimate (Topamax®); Gabapentin (Neurotin®); Valproic acid (Convulex®; Epilim®) – Multiple drug therapies for seizures result in dramatic reductions in blood carnitine levels. (Murry TM, 1996; Columbani P, etal, 1996; Dal Negro R, etal, 1986 & 1988; Beers MH, etal, 1999; Dipalma JR, etal, 1988; Kendler BS, 1986; Del Favero A. 1988; Kobayashi A, etal, 1992)
• AZT (Retrovir®) – depletion or interference of L-carnitne in muscles resulting in muscle damage sometimes cause by its use. (Mancini M, etal, 1992)
• Doxorubicin (Adriblastina®) – L-carnitine may prevent doxorubicin toxicity. (Giovanni M, etal, 1991)

Some references:

Rude RK. Magnesium deficiency: A cause of heterogeneous disease in humans. J Bone Miner Res 1998;13:749-58.

Wester PO. Magnesium. Am J Clin Nutr 1987;45:1305-12.

U.S. Department of Agriculture Agricultural Research Service. Nutrient Database for Standard Reference.

Institute of Medicine. Food and Nutrition Board. Dietary Reference Intakes: Calcium, Phosphorus, Magnesium, Vitamin D and Fluoride. National Academy Press. Washington, DC, 1999.

Kelepouris E and Agus ZS. Hypomagnesemia: Renal magnesium handling. Semin Nephrol 1998;18:58-73.

Ramsay LE, Yeo WW, Jackson PR. Metabolic effects of diuretics. Cardiology 1994;84 Suppl 2:48-56.

Lajer H and Daugaard G. Cisplatin and hypomagnesemia. Ca Treat Rev 1999;25:47-58.

Elisaf M, Bairaktari E, Kalaitzidis R, Siamopoulos K. Hypomagnesemia in alcoholic patients. Alcohol Clin Exp Res 1998;22:244-246.

Abbott L, Nadler J, Rude RK. Magnesium deficiency in alcoholism: Possible contribution to osteoporosis and cardiovascular disease in alcoholics. Alcohol Clin Exp Res 1994;18:1076-82.

Rude RK and Olerich M. Magnesium deficiency: Possible role in osteoporosis associated with gluten-sensitive enteropathy. Osteoporos Int 1996;6:453-61.

Tosiello L. Hypomagnesemia and diabetes mellitus. A review of clinical implications. Arch Intern Med 1996;156:1143-8.

Paolisso G, Scheen A, D'Onofrio F, Lefebvre P. Magnesium and glucose homeostasis. Diabetologia 1990;33:511-4.

Elisaf M, Milionis H, Siamopoulos K. Hypomagnesemic hypokalemia and hypocalcemia: Clinical and laboratory characteristics. Mineral Electrolyte Metab 1997;23:105-112.

Paolisso G, Sgambato S, Gambardella A, Pizza G, Tesauro P, Varricchio H, D'Onofrio F. Daily magnesium supplements improve glucose handling in elderly subjects. Am J Clin Nutr 1992;55:1161-7.

18. American Diabetes Association. Magnesium supplementation in the treatment of diabetes. Diabetes Care 1992:1065-1067.

Appel LJ. Nonpharmacologic therapies thatreduce blood presure: A fresh perspective. Clin Cardiol 1999;22:1111-5.

Simopoulos AP. The nutritional aspects of hypertension. Compr Ther 1999;25:95-100.

Appel LJ, Moore TJ, Obarzanek E, Vollmer WM, Svetkey LP, Sacks FM, Bray GA, Vogt

TM, Cutler JA, Windhauser MM, Lin PH, Karanja N. A clinical trial of the effects of dietary patterns on blood pressure. N Engl J Med 1997;336:1117-24.

Sacks FM, Obarzanek E, Windhauser MM, Svetkey LP, Vommer WM, McCullough M, Karanja N, Lin PH, Steele P, Praschen MA, Evans M, Appel LJ, Bray GA, Vogt T, Moore MD for the DASH investigators. Rationale and design of the Dietary Approaches to Stop Hypertension trial (DASH). A multicenter controlled-feeding study of dietary patterns to lower blood pressure. Ann Epidemiol 1995;5:108-18.

Reusser ME and McCarron DA. Micronutrient effects on blood pressure regulation. Nutr Rev 1994;52:367-75.

Ascherio A, Rimm EB, Giovannucci EL, Colditz GA, Rosner B, Willett WC, Sacks FM, Stampfer MJ. A prospective study of nutritional factors and hypertension among US men. Circulation 1992;86:1475-84.

National Heart, Lung, and Blood Institute. Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. The sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Arch Intern Med 1997;157:2413-46.

Schwartz GL and Sheps SG. A review of the sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Curr Opin Cardiol 1999;14:161-8.

Kaplan NM. Treatment of hypertension: Insights from the JNC-VI report. Am Fam Physician 1998;58:1323-30

Altura BM and Altura BT. Magnesium and cardiovascular biology: An important link between cardiovascular risk factors and atherogenesis. Cell Mol Biol Res 1995;41:347-59.

Caspi J, Rudis E, Bar I, Safadi T, Saute M. Effects of magnesium on myocardial function after coronary artery bypass grafting. Ann Thorac Surg 1995;59:942-7.

Ravn HB, Vissinger H, Kristensen SD, Wennmalm A, Thygesen K, Husted SE. Magnesium inhibits platelet activity--an infusion study in healthy volunteers. Thromb Haemot 1996;75:939-44.

Ford ES. Serum magnesium and ischaemic heart disease: Findings from a national sample of US adults. Intl J of Epidem 1999;28:645-651. 35. Liao F, Folsom A, Brancati F. Is low magnesium concentration a risk factor for coronary heart disease? The Atherosclerosis Risk in Communities (ARIC) Study. Am Heart J 1998;136:480-90.

Gartside P and Glueck C. The important role of modifiable dietary and behavioral characteristics in the causation and prevention of coronary heart disease hospitalization and mortality: The prospective NHANES I follow-up study. J Am Coll Nutr 1995;14:71-79.


Additional reading:

• Uhlenbruck G. L-carnitine and the immune system: from the mode of metabolism to the modulation of membranes. Carnitine – Path Bas and Clin Applic, Ponte press Bochum 1996 page 47-61
• Giovanni M. Agostoni C., Salari PC., Is carnitine essential in children? J Int Med Res 1991;19:88-102.
• Mancini M, Rengo F, Lingetti M, et al. Controlled study on the therapeutic efficacy of propionyl-L-carnitine in patients with congestive heart failure. Arzneimittelforschung 1992;42:1101-4.
• Digiesi V, Palchetti R, Cabtini F. The benefits of L-carnitine in essential arterial hypertension. Minerva Med 1989;80:227-31.
• Murry MT. The any benfits of carnitine. Am J Natural Med 1996;3:6-14 [review].
• Columbani P, Wenk C, Kunz I, etal. Effect of L-carnitine supple mentation on physical performamnce and energy metabolism of endurance-trained athletes: a double blind crossover field study. Eur J Appl Physiol 1996;73:434-9.
• Dal Negro R, Turco P, Pomari C, De Conti F. Effects of L-carnitine on physical performance in chronic respiratory insufficiency. Int J Clin Pharmacol Ther Toxicol 1988;26:269-72.
• Beers MH, Berkow R (eds). The Merck Manual of Diagnosis and Therapy, 17th ed. Whitehouse Station, NJ: Merck and Co., Inc, 1999, 881-3.
• Dipalma JR. Carnitine deficiency. Am Fam Physician 1988;38:243-51.
• Kendler BS. Carnitine: an overview of its role in preventive medicine. Prev Med 1986;15:373-90.
• Tamamogullari N, Silig Y, Icagasioglu S, Atalay A. Carnitine deficiency in diabetes mellitus complications. J Diabetes Complications 1999;13:251-3.
• Del Favero A. Carnitine and gangliosides. Lancet 1988;2:337 [letter].
• Kobayashi A, Masumura Y, Yamazaki N. L-carnitine treatment for congestive heart failure-experimental and clinical study. Jpn Circ J 1992;56:86-94.