Our bodies are made up of tens of trillions of cells.1 They are the fundamental building blocks of our tissues, organs and virtually everything that makes us a living organism. Naturally, it is vital that our cells stay healthy so they can function optimally, including the ability to replicate and make new cells as needed.

Despite the importance of maintaining optimal cellular function, most of us never think about what we can do to help support cellular health. Rather, we think in more macro terms like what we can do to improve the health of our joints or cardiovascular system. However, if we pay some attention improving cellular health, it is more likely that everything will function better. This article will discuss a few nutraceuticals that can play a key role in supporting cellular health. But first, let’s take a brief look at the biology of the cell so that you can better appreciate how the nutraceuticals perform their valuable tasks.

Biology of a Cell 

In general, our cells are comprised of a cell membrane, a nucleus, cytoplasm and various organelles. To understand the role that these components play, it helps to use a chicken egg as an analogy:

• the shell is like the cell membrane, protecting the cell and keeping it everything on the inside that’s supposed to be there

• the yolk is like the nucleus, containing all of the genetic information necessary to reproduce the cell

• the egg white is like the cytoplasm, a gel-like substance that provides internal structure to the cell.

This is not a perfect analogy since there are significant differences between a chicken egg and a cell. For example, eggshells are designed to keep foreign substances out of the egg. Cell membranes, however, are made of phospholipid bilayer with certain proteins embedded in it with pores that allow nutrients to enter and waste material to leave the cell. The membrane also receives and transmits certain biochemical signals. Another example is the various organelles within the cytoplasm are not really analogous to anything within the egg white, yet each of the organelles has important roles to play.

One such organelle is the mitochondrion. Mitochondria can be considered as cellular power plants because they generates adenosine triphosphate (ATP) which cells use as a source of energy.

Phosphatidylserine for Cellular Membrane Support 

Phosphatidylserine (PS) is the most abundant phospholipid in our cell membranes, comprising much of the structure of the phospholipid bilayer.2 Furthermore, PS is not just a passive component of the membrane, but rather plays an important role in the cell's internal environment, signal transduction (activating a specific receptor located on the cell surface or inside the cell), secretory vesicle release (transport of hormones, neurotransmitters or other cargo from an organelle to specific sites at the cell membrane), cell-to-cell communication and cell growth regulation.3,4,5 PS is also a component of the mitochondrial membrane, where it might function as a metabolic reservoir for other phospholipids. 6 Although the body obtains most of its PS from dietary sources, PS is only present in small quantities in most foods.7 Consequently, supplementation provides a viable source of PS, and has been shown in research to affect neuronal membranes, cell metabolism, and specific neurotransmitter systems.8 Given the role of PS in cellular health, it is not surprising that human clinical studies have demonstrated that supplementation has been able to improve:

• age-related memory impairment9-12

• Alzheimer’s and other dementias13-16

• attention-deficit hyperactivity disorder (ADHD) in children17-19

• cognitive function and learning in students20

• depression in geriatric patients21

• muscle soreness associated with exercise and overtraining22-24 

Doses of 100-300 mg PS have been most commonly used in human research.

PQQ and CoQ10 for Mitochondrial Support 

Pyrroloquinoline quinone (PQQ), a natural substance made by the body, is an essential cofactor in important, enzymecatalyzed reduction–oxidation (redox) reactions, including the production of ATP.25 Furthermore, PQQ has been shown to stimulate mitochondrial activity, including the production of new mitochondria (mitochondrial biogenesis). 26 Research in mice demonstrated that those supplemented with PQQ had 20-30 percent more mitochondria than PQQ deficient mice.27 This ability to stimulate the production of new mitochondria has significant ramifications for increasing ATP production (i.e. more mitochondria to make ATP). In addition, PQQ was found to be an effective antioxidant protecting mitochondria against oxidative stress-induced lipid peroxidation, protein carbonyl formation and inactivation of the mitochondrial respiratory chain. In human clinical research, supplementation with PQQ was shown to:

• promote cognitive function29,30

• reduce markers of inflammation31 Doses of 20 mg PQQ have been most commonly used in human research.

Coenzyme Q10 (CoQ10) is found in virtually all cells in the body. Within the cell, 25 to 30 percent of total CoQ10 is found in the nucleus, 40 to 50 percent in mitochondria, 15 to 20 percent in the microsomes and 5 to 10 percent in the cytosol (a major component of cytoplasm). 32,33 CoQ10 acts as an antioxidant, a membrane stabilizer and as a cofactor in many metabolic pathways, particularly in the production of adenosine ATP in mitochondria by functioning as an electron carrier.34-38 In addition, CoQ10 provides a source of needed protons to special digestive enzymes (from lysosomes) that clean up cellular debris within cells,39 and acts as a powerful, fat-soluble antioxidant in cells, inhibiting lipid peroxidation in cell membranes, DNA and low-density lipoproteins (LDL).40 The human clinical research on CoQ10 is far too extensive to summarize in this article.

While a range of CoQ10 doses have been used in human research, supplementation with at least 100 mg of CoQ10 daily is capable of significantly reducing oxidative damage41-43 and promoting energy/physical performance.44,45

Conclusion 

In addition to those presented here, there are many more nutraceuticals that support cellular health. However, given space restrictions, I’ve limited my discussion to the contributing roles of PS, PQQ and CoQ10. Nevertheless, supplementation of these three nutraceuticals has great potential to promote healthy cellular function, especially with regard to mitochondria and ATP production. VR 

Gene Bruno, MS, MHS, the dean of academics for Huntington College of Health Sciences, is a nutritionist, herbalist, writer and educator. For more than 30 years he has educated and trained natural product retailers and health care professionals, has researched and formulated natural products for dozens of dietary supplement companies, and has written articles on nutrition, herbal medicine, nutraceuticals and integrative health issues for trade, consumer magazines and peerreviewed publications.

References:

1. Eveleth R. There are 37.2 Trillion Cells in Your Body. SmartNews Keeping you current. October 24, 2013. Retrieved October 23, 2014 from http://www.smithsonianmag.com/smart-news/there-are-372-trillion-cells-in-your-body-4941473/?no-ist.
2. Leventis PA, Grinstein S. The distribution and function of phosphatidylserine in cellular membranes. Annu Rev Biophys. 2010;39:407-27.
3. Crook T, Petrie W, Wells C, Massari DC. Effects of phosphatidylserine in Alzheimer's disease. Psychopharmacol Bull 1992;28:61-6.
4. Blokland A, Honig W, Brouns F, Jolles J. Cognition-enhancing properties of subchronic phosphatidylserine (PS) treatment in middle-aged rats: comparison of bovine cortex PS with egg PS and soybean PS. Nutrition 1999;15:778-83.
5. Kay JG, Grinstein S. Phosphatidylserine-mediated cellular signaling. Adv Exp Med Biol. 2013;991:177-93.
6. Kidd PM. Phosphatidylserine; Membrane nutrient for memory. A clinical and mechanistic assessment. Altern Med Rev 1996;1:70-84.
7. Pepping J. Phosphatidylserine. Am J Health-Syst Pharm 1999;56:2038,2043-4.
8. Phosphatidylserine. Monograph. Altern Med Rev. 2008 Sep;13(3):245-7.
9. Kato-Kataoka, A., Sakai, M., Ebina, R., Nonaka, C., Asano, T. & Miyamori, T. 2010, ‘Soybean-Derived Phosphatidylserine Improves Memory Function of the Elderly Japanese Subjects with Memory Complaints’, J. Clin. Biochem. Nutr., vol. 47, pp. 246–255.
10. Gindin, J., Novikov, M., Dedar, D., Walter- Ginzburg, A., Naor, S., Levi, S. 2009, ‘The effect of plant phosphtidylserine on age-associated memory impairment and mood in the functioning elderly’, The Geriatric Institute for Education and Research, and Department of Geriatrics, Kaplan Hospital, Rehovot, Israel. Unpublished report.
11. Crook TH. Treatment of Age-Related Cognitive Decline: Effects of Phosphatidylserine. In Klatz RM (Ed.). Anti-Aging Medical Therapeutics, Vol II. Health Quest Publications, Chicago; 1998:20-29.
12. Cenacchi, T., Bertoldin, T., Farina, C., Fiori, M.G., Crepaldi, G., and participating investigators. 1993, ‘Cognitive decline in the elderly: A double-blind, placebo-controlled multicenter study on efficacy of phosphatidyiserine administration’, Aging Clin. Exp. Res., vol. 5, pp. 123-133.
13. Engel, R.R., Satzger, W., Gunther, W., Kathmann N; Bove, D., Gerke, S., Munch, U. & Hippius, H. 1992, ‘Double-blind cross-over study of phosphatidylserine vs. placebo in patients with early dementia of the Alzheimer type’European Neuropsychopharmacology, vol. 2, no. 2, pp. 149-55.
14. Delwaide, P.J., Gyselynck-Mambourg, A.M., Hurlet, A. & Ylieff, M. 1986, ‘Double-blind randomized controlled study of phosphatidylserine in senile demented patients’, Acta Neurologica Scandinavica, vol. 73, no. 2, pp. 136-40.
15. Funfgeld, E.W., Baggen, M., Nedwidek, P., Richstein, B. & Mistlberger, G. 1989, ‘Double-blind  study with phosphatidylserine (PS) in parkinsonian patients with senile dementia of Alzheimer's type (SDAT)’,  Progress in Clinical and Biological Research, vol. 317, pp. 1235-46.
16. Rabboni, M., Maggioni, F.S., Giannelli, A. & Beinat, L. 1990, ‘Neuroendocrine and behavioural effects of phosphatidylserine in elderly patients with abiotrophic or vascular dementia or mild depression. A preliminary trial’, Clin Trials J, vol. 27, no. 3, pp. 230-240.
17. Hirayama S, Masuda Y, Rabeler R. Effect of phosphatidylserine administration on symptoms of attention-deficit/hyperactivity disorder in children. AgroFOOD. 2006; 17(5):16-20.
18. Hirayama S, Terasawa K, Rabeler R, Hirayama T, Inoue T, Tatsumi Y, Purpura M, Jäger R. The effect of phosphatidylserine administration on memory and symptoms of attention-deficit hyperactivity disorder: a randomised, double-blind, placebo-controlled clinical trial. J Hum Nutr Diet. 2014 Apr;27 Suppl 2:284-91.
19. Kidd P. Attention Deficit/Hyperactivity Disorder (ADHD) in Children: Rationale for Its Integrative Management. Altern Med Rev 2000; 5(5):402-428.
20. Yong T, Qianyong Z, Mantian M, Gang H, Jing W. Research on human memory enhancement by phosphatidylserine fortified milk. Chongqing Medicine. 2011;30.003. doi: 10.3969.
21. Maggioni M, Picotti GB, Bondiolotti GP, et al. Effects of phosphatidylserine therapy in geriatric patients with depressive disorders. Acta Psychiatr Scand 1990;81:265-70.
22. Fahey TD, Pearl MS. The hormonal and perceptive effects of phosphatidylserine administration during two weeks of resistive exercise-induced overtraining. Biol Sport 1998;15:135-44.
23. Monteleone P, Beinat L, Tanzillo C, et al. Effects of phosphatidylserine on the neuroendocrine response to physical stress in humans. Neuroendocrinology 1990;52:243-8.
24. Monteleone P, Maj M, Beinat L, et al. Blunting by chronic phosphatidylserine administration of the stress-induced activation of the hypothalamo-pituitary-adrenal axis in healthy men. Eur J Clin Pharmacol 1992;42:385-8.
25. Kasahara T, Kato T. Nutritional biochemistry: A new redox-cofactor vitamin for mammals. Nature. 2003 April 24;422(6934):832.
26. Chowanadisai W, Bauerly KA, Tchaparian E, Wong A, Cortopassi GA, Rucker RB. Pyrroloquinoline quinone stimulates mitochondrial biogenesis through cAMP response element-binding protein phosphorylation and increased PGC-1alpha expression. J Biol Chem. 2010 Jan 1;285(1):142-52.
27. Stites T, Storms D, Bauerly K, et al. Pyrroloquinoline quinone modulates mitochondrial quantity and function in mice. J Nutr. 2006 Feb;136(2):390-6.
28. He K, Nukada H, Urakami T, Murphy MP. Antioxidant and pro-oxidant properties of pyrroloquinoline quinone (PQQ): implications for its function in biological systems. Biochem Pharmacol. 2003 Jan 1;65(1):67-74.
29. Nakano M, et al. Effect of pyrroloquinoline quinone (PQQ) on mental status of middle-aged and elderly persons. [Japanese] Food Style 21. 2009;13(7):50-3.
30. Koikeda T, NereNo M, and Masuda K. Pyrroloquinoline quinone disodium salt improves higher brain function. Medical Consultation and New Remedies. 2011. 48(5):519.
31. Harris CB1, Chowanadisai W, Mishchuk DO, Satre MA, Slupsky CM, Rucker RB. Dietary pyrroloquinoline quinone (PQQ) alters indicators of inflammation and mitochondrial-related metabolism in human subjects. J Nutr Biochem. 2013 Dec;24(12):2076-84.
32. Greenberg S, Frishman WH. Co-enzyme Q10: a new drug for cardiovascular disease. J Clin Pharmacol 1990;30:596-608
33. Turunen M, Olsson J, Dallner G. Metabolism and function of coenzyme Q. Biochim Biophys Acta 2004;1660:171-99.
34. Greenberg S, Frishman WH. Co-enzyme Q10: a new drug for cardiovascular disease. J Clin Pharmacol 1990;30:596-608.
35. Watson PS, Scalia GM, Galbraith A, et al. Lack of effect of coenzyme Q on left ventricular function in patients with congestive heart failure. J Am Coll Cardiol 1999;33:1549-52.
36. Heck AM, DeWitt BA, Lukes AL. Potential interactions between alternative therapies and warfarin. Am J Health Syst Pharm 2000;57:1221-7.
37. Pizzorno JE, Murray MT, eds. Textbook of Natural Medicine. 2nd ed. New York: Churchill Livingston, 1999.
38. Turunen M, Olsson J, Dallner G. Metabolism and function of coenzyme Q. Biochim Biophys Acta 2004;1660:171-99.
39. Nohl H, Gille L. The role of coenzyme Q in lysosomes. In: Kagan VEQ, P. J. (ed). Coenzyme Q: Molecular Mechanisms in Health and Disease. Boca Raton: CRC Press; 2001:99-106.
40. Ernster L, Dallner G. Biochemical, physiological and medical aspects of ubiquinone function. Biochim Biophys Acta. 1995;1271(1):195-204.
41. Gül I, Gökbel H, Belviranli M, Okudan N, Büyükbaş S, Başarali K. Oxidative stress and antioxidant defense in plasma after repeated bouts of supramaximal exercise: the effect of coenzyme Q10. J Sports Med Phys Fitness. 2011 Jun;51(2):305-12.
42. Sakata T, Furuya R, Shimazu T, Odamaki M, Ohkawa S, Kumagai H. Coenzyme Q10 administration suppresses both oxidative and antioxidative markers in hemodialysis patients. Blood Purif. 2008;26(4):371-8.
43. Lee BJ, Huang YC, Chen SJ, Lin PT. Coenzyme Q10 supplementation reduces oxidative stress and increases antioxidant enzyme activity in patients with coronary artery disease.Nutrition. 2012 Mar;28(3):250-5.
44. Ylikoski T, Piirainen J, Hanninen O, Penttinen J. The effect of coenzyme Q10 on the exercise performance of cross-country skiers. Mol Aspects Med. 1997;18 Suppl:S283-90.
45. Gökbel H, Gül I, Belviranl M, Okudan N. The effects of coenzyme Q10 supplementation on performance during repeated bouts of supramximal exercise in sedentary men. Journal of Strength and Conditioning Research; Jan 2010; 24(1):97-102.