How Does It Work?:
Background
The Krebs cycle, also known as the citric acid cycle or the tricarboxylic acid (TCA) cycle, was first identified by Hans Adolf Krebs in 1937. The Krebs cycle consists of a series of enzymatic reactions, which use oxygen to convert carbohydrates, proteins, and fats into carbon dioxide and water. The cycle is also responsible for the generation of cellular energy in the form of adenosine triphosphate (ATP). ATP is a nucleotide utilized to transport energy for cell metabolism. Each turn of the cycle generates one molecule of ATP and two molecules of carbon dioxide (CO2). The Krebs cycle takes place within the mitochondria, distinct organelles found inside every cell and commonly referred to as the “energy powerhouse”.¹

The Krebs cycle consists of 8 critical steps involving the creation of 5 intermediate compounds:

1. Acetyl coenzyme A (acetyl CoA), a product of glycolysis (the first step in the breakdown of glucose), is one of the starting components of the Krebs cycle. The acetic acid subunit of acetyl CoA is combined with oxaloacetate to form citrate. The coenzyme subunit of acetyl CoA is released by hydrolysis (a reaction with water) to combine with another acetic acid molecule and begin the Krebs cycle again. ¹
   
    
2. Citrate is converted into its isomer isocitrate. Isomers are molecules possessing the same chemical formula, but different structural configurations.¹
   
    
3. Isocitrate is oxidized to form the second intermediate, alpha-ketoglutarate. During this reaction, carbon dioxide (CO2) is released and nicotinamide adenine dinucleotide (NAD+), an important coenzyme and carrier of electrons in the electron transport chain, is reduced to NADH. This transfer of electrons is critical to the generation of cellular energy.¹
   
    
4. Alpha-ketoglutarate is oxidized to succinyl coenzyme A (succinyl CoA). A second molecule of CO2 is released and another molecule of NADH is formed.¹
   
    
5. A water (H2O) molecule donates its hydrogen atoms to the coenzyme A subunit of succinyl CoA. Then, a free-floating phosphate group (-PO4) displaces coenzyme A and forms a bond with the succinyl complex. The phosphate is then transferred to a molecule of adenosine diphosphate (ADP) to produce an energy molecule of adenosine triphosphate (ATP). It leaves behind one molecule of succinate.¹
   
    
6. Succinate is oxidized by a molecule of flavin adenine dinucleotide (FAD), another compound necessary for the transfer or electrons and generation of energy within the cell. The intermediate fumarate is formed and FADH, the reduced form of FAD, is released.1
   
    
7. Fumarate is hydrolyzed (by water) to form the final intermediate, malate.¹
   
    
8. Malate is oxidized by NAD+ to regenerate the Krebs cycle starting component, oxaloacetate. Another molecule of NADH is formed. Oxaloacetate is then free to combine with acetyl CoA and begin the Krebs cycle again.¹

The Krebs cycle intermediates include the five organic acids: citrate, alpha ketoglutarate, succinate, fumarate, and malate. Research suggests that minerals chelated (bound) to these intermediates, like those found in Krebs Cycle Chelates, have several advantages over other mineral forms.

Krebs cycle intermediates are readily absorbed and utilized by the body. These complexes are more easily ionized than other mineral forms. This ability to dissociate (break apart into positive cations and negative anions) increases the amount of ionized minerals available for uptake by the body. Krebs cycle intermediates are also very stable over the broad pH range found in the gastrointestinal tract. As a result, the net absorption of mineral cations is far greater with Krebs cycle intermediates than with other mineral complexes.¹

Supplementation with Krebs cycle chelated-minerals is often used to enhance the mitochondrial production of cellular energy.^†2 Sustainable energy is especially important in tissues requiring high levels of energy, such as the heart, arteries, and veins.^†3

The following table details the benefits of each ingredient found in Krebs Cycle Chelates:

 

References:
 

1. Lehninger AL, Nelson DL, Cox MM. The Citric Acid Cycle. In: Principles of Biochemistry, 2nd ed. New York City, NY: Worth Publishers; 1993:446-74.
2. Marconi C Sassi G The effect of an alpha-ketoglutarate-pyridoxine complex on human maximal aerobic and anaerobic performance. Eur J Appli Phys. 1982;49(3):307-17.
3. Wiesner RJ et al The anaerobic heart: succinate formation and mechanical performance. Exp Biol. 1986;45(1):55-64.
4. Wan B, LaNoue KF, Cheung JY, Scaduto RC Jr. Regulation of citric acid cycle by calcium. J Biol Chem. 1989 Aug 15;264(23):13430-9.
5. Schaffer SW, Tan BH. Effect of calcium depletion and calcium paradox on myocardial energy metabolism. Can J Physiol Pharmacol. 1985 Nov;63(11):1384-91.
6. Tortora GJ, Grabowski SR. Principles of Anatomy and Physiology. 8th ed. New York, NY. Harper and Row. 1996:837-838.
7. Ece A, Yigitoglu MR, Vurgun N, Guven H, Iscan A. Serum lipid and lipoprotein profile in children with iron deficiency anemia. Pediatr Int. 1999 Apr;41(2):168-73.
8. Beck-da-Silva L, Rohde LE, Pereira-Barretto AC, de Albuquerque D, Bocchi E, Vilas-Boas F, Moura LZ, Montera MW, Rassi S, Clausell N. Rationale and design of the IRON-HF study: a randomized trial to assess the effects of iron supplementation in heart failure patients with anemia. J Card Fail. 2007 Feb;13(1):14-7.
9. Galloe AM, Rolff M, Nordin H, Ladefoged SD, Mogensen NB. Cardiac performance and thyroid function. The correlation between systolic time intervals, heart rate and thyroid hormone levels. Dan Med Bull. 1993 Sep;40(4):492-5.
10. Michailova AP, Belik ME, McCulloch AD. Effects of magnesium on cardiac excitation-contraction coupling. J Am Coll Nutr. 2004 Oct;23(5):514S-517S.
11. Pansin P, Wathanavaha A, Tosukhowong P, et al. Magnesium and zinc status in survivors of sudden unexplained death syndrome in northeast Thailand. Southest Asian J Trop Med Public Health. 2002;1:172-9.
12. Tohno S, Tohno Y, Moriwake Y, et al. Compositional changes of the aortic valve similar to the artery with aging. Biol Trace Elem Res. 2002;1-3:83-93.
13. Bhaskar M, Madhuri E, Abdul Latheef SA, Subramanyam G. Influence of zinc on cardiac and serum biochemical parameters in rabbits. Indian J Exp Biol. 2001;11:1170-2.
14. Alissa EM, Bahijri SM, Ferns GA. The controversy surrounding selenium and cardiovascular disease: a review of the evidence. Med Sci Monit. 2003;1:RA9-18.
15. Elsherif L, Ortines RV, Saari JT, Kang YJ. Congestive heart failure in copper deficient mice. Exp Biol Med (Maywood). 2003;7:811-17.
16. Medeiros DM, Wildman RE. Newer findings on a unified perspective of copper restriction and cardiomyopathy. Exp Biol Med. 1997;215:299-313.
17. Heller LJ, Mohrman DE, Prohaska JR. Decreased passive stiffness of cardiac myocytes and cardiac tissue from copper deficient rat hearts. Am J Physiol Heart Physiol.2000;8:H1840-H1847.
18. Fleming T., ed. Manganese In: PDRฎ for Nutritional Supplements. Montvale, NJ: Medical Economics Company; 2001: 296-298.
19. Naya FJ, Black BL, Wu H, et al. Mitochondrial deficiency and cardiac sudden death in mice lacking the MEF2A transcription factor. Natur Med. 2002;11:1303-09.
20. Fleming T., ed. Molybdenum In: PDRฎ for Nutritional Supplements. Montvale, NJ: Medical Economics Company; 2001: 308-311.
21. Mendel RR. The role of the molybdenum cofactor in humans. BioFactors. 2000;11:147-148.
22. Liu DL, Yan M, Chua YL, Chen C, Lim YL. Effects of molybdenum, silicon and nickel on alpha1-adrenoceptor induced constriction of rat isolated aorta. Clin Exp Pharmacol Physiol. 2002;5-6:395-98.
23. Rowland E, Krikler DM. Potassium supplementation in the treatment of ventricular arrhythmias. Acta Med Scand Suppl. 1981;647:95-100.
24. Samman S, Naghii MR, Lyons Wall PM, Verus AP. The nutritional and metabolic effects of boron in humans and animals. Biol Trace Elem Res. 1998 Winter;66(1-3):227-35.
25. Noda C, Masuda T, Sato K, Ikeda K, Shimohama T, Matsuyama N, Izumi T. Vanadate improves cardiac function and myocardial energy metabolism in diabetic rat hearts. Jpn Heart J. 2003 Sep;44(5):745-57.
26. Barceloux DG. Vanadium. J Toxicol Clin Toxicol. 1999;2:265-78.
27. Carmignani M, Volpe AR, Masci O, et al. Vanadate as factor of cardiovascular regulation by interactions with the catecholamine and nitric oxide systems. Biol Trace Elem Res. 1996;1:1-12.