Life Extension Magazine December 2006
As We See It
Stem Cell Therapy in a Pill?
By William Faloon
By William Faloon
In November 2001, Dr. Michael West made a startling announcement. Dr. West’s laboratory, Advanced Cell Technology, had just created the first human embryonic stem cells, and this breakthrough had been published in the Journal of Regenerative Medicine.
Dr. West’s announcement became instant headline news around the world. Scientists at Advanced Cell Technology made it clear that their intention was “not to create cloned human beings, but rather to make lifesaving therapies for a wide range of human disease conditions, including diabetes, strokes, cancer, AIDS, and neurodegenerative disorders such as Parkinson’s and Alzheimer’s disease.”1
Instead of heralding Dr. West’s discovery as a major scientific advance, the federal government tried to outlaw human embryonic stem cell research altogether. While the government failed to enact criminal penalties against stem cell scientists, it did manage to ban embryonic stem cell research in facilities that received government funding.2 The result of this prohibition is that very few stem cell therapies are available to the millions of Americans whose lives might otherwise be saved by them.
For the past five years, longevity enthusiasts have deluged Congress with letters seeking to lift the ban on embryonic stem cell research.
Nutrients Promote Stem Cell Proliferation
The tissue that scientists most associate with adult stem cell activity is the bone marrow. Each day, stem cells in the bone marrow evolve to produce red blood cells, white blood cells, and platelets. These mature cells are then released into the bloodstream where they perform their vital life-supporting functions.
When bone marrow stem cell activity is interfered with, diseases such as anemia (red blood cell deficit), neutropenia (specialized white blood cell deficit), or thrombocytopenia (platelet deficit) are often diagnosed. Any one of these conditions can cause death if not corrected.
Scientists have long known that folic acid, vitamin B12, and iron are required for bone marrow stem cells to differentiate into mature red blood cells.3-7 Vitamin D has been shown to be crucial in the formation of immune cells,8-11 whereas carnosine has demonstrated a remarkable ability to rejuvenate cells approaching senescence and extend cellular life span.12-28
Other studies of foods such as blueberries show this fruit can prevent and even reverse cell functions that decline as a result of normal aging.29-36 Blueberry extract has been shown to increase neurogenesis in the aged rat brain.37,38 Green tea compounds have been shown to inhibit the growth of tumor cells, while possibly providing protection against normal cellular aging.39,40
Based on these findings, scientists are now speculating that certain nutrients could play important roles in maintaining the healthy renewal of replacement stem cells in the brain, blood, and other tissues. It may be possible, according to these scientists, to use certain nutrient combinations in the treatment of conditions that warrant stem cell replacement.41-43
Theories Put to the Test
To test the hypothesis that nutrients may promote healthy stem cell proliferation, scientists screened a wide range of whole-food extracts, herbal extracts, and specific compounds.43 The objective was to promote hematopoietic stem cell proliferation. Hematopoietic stem cells are adult stem cells that are used routinely for bone marrow transplantation. They reside in bone marrow and are capable of generating all cell types of the blood and immune system.
In this study, spinach, spirulina, astragalus, and other plant compounds did not show a high activity for promoting human bone marrow cell proliferation. Blueberry, green tea, vitamin D3, and carnosine, however, were found to increase bone marrow cell activity in a dose-dependent manner.43
A common side effect of cancer chemotherapy drugs is bone marrow damage, leading to immune suppression and other blood disorders. Medical oncologists routinely prescribe expensive drugs such as granulocyte-macrophage colony-stimulating factor (GM-CSF)—which is also naturally produced by the bone marrow—to stimulate bone marrow stem cell activity. These drug treatments are not without risks of side effects.44
The scientists in this study used GM-CSF as a positive control from which to evaluate the stem cell-promoting effects of various nutrient combinations. As expected, GM-CSF increased bone marrow cell proliferation by around 46%, which was better than any single nutrient compound tested.43
When combinations of nutrients were tested, however, a greater percentage of bone marrow cell proliferation occurred compared to GM-CSF. For example, a combination of blueberry and vitamin D3 exhibited a 62% increase in proliferation of bone marrow cells.43 Blueberry and catechin (green tea extract) increased bone marrow cell proliferation by 70%. When carnosine and blueberry were combined, the growth promotion observed was 83% . . . an effect significantly greater than that of the expensive drug GM-CSF!43
The scientists next tested various nutrients on early stem cells, which can be identified and isolated by their surface antigen-receptor expressions (e.g., CD34 + and CD 133 +). The GM-CSF drug increased these early stem cells by 48%, as expected. A combination of blueberry, green tea, vitamin D3, and carnosine, however, increased these stem cells by an astounding 68%.43
These studies, published just this year, demonstrate for the first time that various natural compounds can promote the proliferation of human bone marrow cells and human stem cells. While these studies were done in vitro, they provide evidence that readily available nutrients may confer a protective effect against today’s epidemic of age-related bone marrow degeneration.
What These Studies Mean to Aging Adults
People afflicted with degenerative illnesses have endured daily suffering that could have been treated effectively had embryonic stem cell research not been stymied by our own government.
Elderly people endure defective immune function that makes them vulnerable to infectious disease, cancer, and chronic inflammatory conditions. Anemia is so prevalent among the elderly that doctors routinely overlook life-threatening red blood cell deficiencies in their older patients, which results in needless heart and brain damage.45
Embryonic stem cells are capable of generating all differentiated cell types in the body. If embryonic stem cell therapies were readily available today, the incidence of a number of age-related diseases would plummet. Regrettably, federal bureaucracies have stifled the advancement of human therapeutic embryonic stem cell research, and caused millions of Americans to suffer and die needlessly.
A few scientists have begun to experiment with the use of adult (bone marrow) stem cells to help treat a wide variety of diseases. Adult stem cells are often tissue-specific and can generate only the cell types comprising a particular tissue in the body; however, in some cases, they can trans-differentiate into cell types found in other tissues. Unfortunately, these therapies have not yet been fully developed and are largely unavailable to the vast majority of Americans.46
The encouraging news is that many of the nutrients that Life Extension members already use may serve to maintain youthful bone marrow stem cell production. It would be fascinating to see a clinical trial in aging humans to determine whether ingesting vitamin D3, blueberry, green tea, and carnosine can reverse anemia, immune deficiencies, and other bone marrow disorders.
For longer life,
1. Available at: http://archives.cnn.com/2001/TECH/science/11/25/human.embryo.clone. Accessed August 2, 2006.
2. Available at: http://www.hmnews.org/article2778.html. Accessed August 2, 2006.
3. Koury MJ, Ponka P. New insights into erythropoiesis: the roles of folate, vitamin B12, and iron. Annu Rev Nutr. 2004;24:105-31.
4. Fang TC, Alison MR, Cook HT, et al. Proliferation of bone marrow-derived cells contributes to regeneration after folic acid-induced acute tubular injury. J Am Soc Nephrol. 2005 Jun;16(6):1723-32.
5. Craciunescu CN, Brown EC, Mar MH, et al. Folic acid deficiency during late gestation decreases progenitor cell proliferation and increases apoptosis in fetal mouse brain. J Nutr. 2004 Jan;134(1):162-6.
6. Zittoun J. Anemias due to disorder of folate, vitamin B12 and transcobalamin metabolism. Rev Prat. 1993 Jun 1;43(11):1358-63.
7. Fishman SM, Christian P, West KP. The role of vitamins in the prevention and control of anaemia. Public Health Nutr. 2000 Jun;3(2):125-50.
8. Mathieu C, van EE, Decallonne B, et al. Vitamin D and 1,25-dihydroxyvitamin D3 as modulators in the immune system. J Steroid Biochem Mol Biol. 2004 May;89-90(1-5):449-52.
9. Hypponen E. Micronutrients and the risk of type 1 diabetes: vitamin D, vitamin E, and nicotinamide. Nutr Rev. 2004 Sep;62(9):340-7.
10. Gysemans CA, Cardozo AK, Callewaert H, et al. 1,25-Dihydroxyvitamin D3 modulates expression of chemokines and cytokines in pancreatic islets: implications for prevention of diabetes in nonobese diabetic mice. Endocrinology. 2005 Apr;146(4):1956-64.
11. Aslam SM, Garlich JD, Qureshi MA. Vitamin D deficiency alters the immune responses of broiler chicks. Poult Sci. 1998 Jun;77(6):842-9.
12. Wang AM, Ma C, Xie ZH, Shen F. Use of carnosine as a natural anti-senescence drug for human beings. Biochemistry (Mosc.). 2000 Jul;65(7):869-71.
13. Brownson C, Hipkiss AR. Carnosine reacts with a glycated protein. Free Radic Biol Med. 2000 May 15;28(10):1564-70.
14. McFarland GA, Holliday R. Retardation of the senescence of cultured human diploid fibroblasts by carnosine. Exp Cell Res. 1994 Jun;212(2):167-75.
15. McFarland GA, Holliday R. Further evidence for the rejuvenating effects of the dipeptide L-carnosine on cultured human diploid fibroblasts. Exp Gerontol. 1999 Jan;34(1):35-45.
16. Yuneva MO, Bulygina ER, Gallant SC, et al. Effect of carnosine on age-induced changes in senescence-accelerated mice. J Anti-Aging Med. 1999;2(4):337-42.
17. Hipkiss AR, Preston JE, Himsworth DT, et al. Pluripotent protective effects of carnosine, a naturally occurring dipeptide. Ann NY Acad Sci. 1998 Nov 20;854:37-53.
18. Holliday R, McFarland GA. A role for carnosine in cellular maintenance. Biochemistry (Mosc.). 2000 Jul;65(7):843-8.
19. Shao L, Li QH, Tan Z. L-carnosine reduces telomere damage and shortening rate in cultured normal fibroblasts. Biochem Biophys Res Commun. 2004 Nov 12;324(2):931-6.
20. Yuneva AO, Kramarenko GG, Vetreshchak TV, Gallant S, Boldyrev AA. Effect of carnosine on Drosophila melanogaster life span. Bull Exp Biol Med. 2002 Jun;133(6):559-61.
21. Hipkiss AR, Brownson C, Bertani MF, Ruiz E, Ferro A. Reaction of carnosine with aged proteins: another protective process? Ann NY Acad Sci. 2002 Apr;959:285-94.
22. Stuerenburg HJ. The roles of carnosine in aging of skeletal muscle and in neuromuscular diseases. Biochemistry (Mosc.). 2000 Jul;65(7):862-5.
23. Gallant S, Semyonova M, Yuneva M. Carnosine as a potential anti-senescence drug. Biochemistry (Mosc.). 2000 Jul;65(7):866-8.
24. Boldyrev A, Song R, Lawrence D, Carpenter DO. Carnosine protects against excitotoxic cell death independently of effects on reactive oxygen species. Neuroscience. 1999;94(2):571-7.
25. Boldyrev AA, Gallant SC, Sukhich GT. Carnosine, the protective, anti-aging peptide. Biosci Rep. 1999 Dec;19(6):581-7.
26. Preston JE, Hipkiss AR, Himsworth DT, Romero IA, Abbott JN. Toxic effects of beta-amyloid(25-35) on immortalised rat brain endothelial cell: protection by carnosine, homocarnosine and beta-alanine. Neurosci Lett. 1998 Feb 13;242(2):105-8.
27. Boldyrev AA, Stvolinsky SL, Tyulina OV, et al. Biochemical and physiological evidence that carnosine is an endogenous neuroprotector against free radicals. Cell Mol Neurobiol. 1997 Apr;17(2):259-71.
28. Horning MS, Blakemore LJ, Trombley PQ. Endogenous mechanisms of neuroprotection: role of zinc, copper, and carnosine. Brain Res. 2000 Jan 3;852(1):56-61.
29. Braser P. Blueberries may aid balance, memory. Associated Press. September 17, 1999.
30. Galli RL, Bielinski DF, Szprengiel A, Shukitt-Hale B, Joseph JA. Blueberry supplemented diet reverses age-related decline in hippocampal HSP70 neuroprotection. Neurobiol Aging. 2006 Feb;27(2):344-50.
31. Andres-Lacueva C, Shukitt-Hale B, Galli RL, et al. Anthocyanins in aged blueberry-fed rats are found centrally and may enhance memory. Nutr Neurosci. 2005 Apr;8(2):111-20.
32. Wang Y, Chang CF, Chou J et al. Dietary supplementation with blueberries, spinach, or spirulina reduces ischemic brain damage. Exp Neurol. 2005 May;193(1):75-84.
33. de RC, Shukitt-Hale B, Joseph JA, Mendelson JR. The effects of antioxidants in the senescent auditory cortex. Neurobiol Aging. 2006 Jul;27(7):1035-44.
34. Willis L, Bickford P, Zaman V, Moore A, Granholm AC. Blueberry extract enhances survival of intraocular hippocampal transplants. Cell Transplant. 2005;14(4):213-23.
35. Lau FC, Shukitt-Hale B, Joseph JA. The beneficial effects of fruit polyphenols on brain aging. Neurobiol Aging. 2005 Dec;26 Suppl 1:128-32.
36. Matchett MD, MacKinnon SL, Sweeney MI, Gottschall-Pass KT, Hurta RA. Blueberry flavonoids inhibit matrix metalloproteinase activity in DU145 human prostate cancer cells. Biochem Cell Biol. 2005 Oct;83(5):637-43.
37. Casadesus G, Shukitt-Hale B, Stellwagen HM, et al. Modulation of hippocampal plasticity and cognitive behavior by short-term blueberry supplementation in aged rats. Nutr Neurosci. 2004 Oct;7(5-6):309-16.
38. Joseph JA, Shukitt-Hale B, Denisova NA, et al. Reversals of age-related declines in neuronal signal transduction, cognitive, and motor behavioral deficits with blueberry, spinach, or strawberry dietary supplementation. J Neurosci. 1999 Sep 15;19(18):8114-21.
39. Chen ZP, Schell JB, Ho CT, Chen KY. Green tea epigallocatechin gallate shows a pronounced growth inhibitory effect on cancerous cells but not on their normal counterparts. Cancer Lett. 1998 Jul 17;129(2):173-9.
40. Wang YC, Bachrach U. The specific anti-cancer activity of green tea (-)-epigallocatechin-3-gallate (EGCG). Amino Acids. 2002;22(2):131-43.
41. Whetton AD, Spooncer E. Role of cytokines and extracellular matrix in the regulation of haemopoietic stem cells. Curr Opin Cell Biol. 1998 Dec;10(6):721-6.
42. Gemma C, Mesches MH, Sepesi B, et al. Diets enriched in foods with high antioxidant activity reverse age-induced decreases in cerebellar beta-adrenergic function and increases in proinflammatory cytokines. J Neurosci. 2002 Jul 15;22(14):6114-20.
43. Bickford PC, Tan J, Shytle RD, et al. Nutraceuticals synergistically promote proliferation of human stem cells. Stem Cells Dev. 2006 Feb;15(1):118-23.
44. Demetri GD, Griffin JD. Granulocyte colony-stimulating factor and its receptor. Blood. 1991 Dec 1;78(11):2791-808.
45. Available at: http://www.aafp.org/afp/20001001/1565.html. Accessed August 2, 2006.
46. Available at: http://www.cnn.com/2006/TECH/science/06/07/harvard.cloning.ap/index.html. Accessed August 2, 2006.