About this time last year I was published in a major medical publication with my esteemed colleagues Dr. Harry Adelson, ND and Dr. Paul Anderson, ND. You may recall Dr. Harry from my Pain-Free & Strong Summit this past spring. He is a mentor and dear friend. Dr. Anderson is an all-around rockstar in our profession. I was honored to be included in this paper.
The three of us wrote an article in The Pain Practitioner, the publication of the American Academy of Pain Management. My portion of the article was, unfortunately, cut very short. I hear this is par for the course in the scientific literature world. I was in charge of, you guessed it,“Exercise, Hormones and Nutrition”.
Here is the published version:
Stem Cell Optimization
It turns out that we all have a naturally occurring, or endogenous, supply of stem cells circulating all throughout our bodies. They live in all of our organ systems, including our joints and circulate in our blood. One would assume that the younger the patient, the more stem cells they have floating around for use. This may not be the entire story, however.
I would argue that the HEALTHIER the patient, regardless of age, the better their stem cells will signal and respond, no matter how many you have. This means that we can directly affect our stem cells to work optimally in our favor! I find this to be true in practice every day. THIS is the ticket to true healing, pain relief and anti-aging!
Patients come back singing my praises for the excellent results they have after receiving Regenerative Injection Therapies like Prolotherapy or Platelet Rich Plasma (PRP) treatments. While the doctor performing the treatment has a lot to do with the outcomes in terms of diagnosis and technique, the real credit should go to the patient. Excellent outcomes have as much to do with the patient’s overall health as they do with my skills.
Nutrition & Stem Cells
As would be expected, a nutritionally optimized individual will undoubtedly benefit more from stem cell therapies than a poorly nourished one. Patients who eat a variety of whole foods, adequate protein, omega-3 [i] and other healthy fats, as well as nutrient dense vegetables and leafy greens increase a favorable outcome with stem cell therapies.
Dietary protein allows for increased amino acids as well as zinc in the body to aide in the efforts of collagen deposition [ii,iii] .
Vitamin C from food sources also improve collagen status [iv]. Dietary collagen ingestion from animal sources is highly encouraged for aiding in collagen and cartilage synthesis.
Diets high in refined carbohydrates and sugar hinder healing and the immune system [v].
Patients with impaired blood sugar handling do not respond as well to treatment. Impaired wound healing and increased infection risk are well known in diabetics [vi]. These patients do not do as well clinically with regenerative injection therapies as a whole.
As a good portion of Americans are dealing with some level of obesity and blood sugar dysregulation, nutritional intervention can go a long way in helping these patients not only manage their musculoskeletal pain but improve their outcomes with regenerative and stem cell therapies.
A varied diet of nutritionally dense whole foods, high in protein and healthy fats, and low in refined carbohydrates and other inflammatory grains will ensure that optimal tissue and blood status is achieved by supplying the body with necessary macro and micronutrients for best clinical outcomes.
Hormones & Stem Cells
Hormones affect nearly every cellular processes in the body and rightly have an impact on clinical outcomes in stem cell therapies. To clinically optimize a patient to receive regenerative injection and stem cell therapies, it is important to consider their hormonal status overall.
Tissue optimization by way of nutrition has been discussed and these strategies will assist in the balancing of the hormonal status overall. As this is a huge body of information, for the sake of regenerative injection therapies we will focus on the anabolic steroid testosterone and the metabolic steroid thyroid. Optimization of these hormones may lead to improved outcomes in stem cell therapies.
Testosterone is anabolic and as such promotes tissue deposition and growth. This is well accepted and has been shown in the literature. The very premise of its anabolic effects logically lends itself to being helpful in orthopedic regenerative practices.
Testosterone is being used as an injectate to stimulate tissues locally in prolotherapy treatments for ligamentous laxity with good results [xv]. Testosterone has been shown to increase circulating endothelial progenitor cell numbers in men with late onset hypogonadism as well as promotes angiogenesis by increasing stromal cell-derived factor 1a (SDF-1a) and vascular endothelial growth factor (VEGF) [xvi, xvii]. This is but one mechanism that impacts stem cell therapy outcomes.
Testosterone’s beneficial androgenic effects on wound healing, immune status and inflammatory responses during acute wound healing have all been well documented [xviii, xix].
Thyroid hormone is a metabolic hormone that is a known stimulator of growth and metabolic rate. When thyroid is subclinically or clinically low it leads to decreased wound healing in patients. Even topical use of the hormone has been shown to increase healing [xx].
It is logical to assume that without optimal thyroid hormone status that stem cell therapies will not be as effective. In mammals it has been shown that stem cell proliferation is decreased, as is mitosis, due to hypothyroidism [xxi].
There are other known critical hormones that impact stem cell development, viability and differentiation in the body. The hormonal milieu of a patient is critical and should be clinically addressed prior to administration of stem cell therapies for optimal outcomes in treatment.
Exercise and Stem Cells
Exercise may be the single most powerful tool that we mammals have for self preservation, health and longevity. There is no food source, supplement or medical treatment with such broad sweeping health benefits as exercise. Specifically, Strength/Resistance training to increase skeletal muscle mass indeed earns its title as the fountain of youth.
From increasing mitochondrial output as well as synthesis of new mitochondria, to improving blood sugar handling and insulin levels, strength training exercise is the all-around winner with the most broad reaching benefits of any medical intervention.
The effects of strength training on increasing Human Growth Hormone and testosterone levels are well known [vii, viii]. Mitochondrial synthesis happens in the face of a stressor on the body. Through stimulation of AMPK (amp-activated protein kinase) we see increases in mitochondrial biogenesis. AMPK is produced in the body as a response to a lack of cellular energy and an adaption to an applied stress such as fasting, ketosis and exercise [ix, x]. Exercise also reverses the inhibition of neural stem cells caused by alcohol consumption [xi].
Exercise also improves the structure and way mammalian collagen is laid down [xii] , which is beneficial following orthopedic regenerative injection therapies. Cartilage needs a certain amount of load for chondrocyte health as well as muscular integrity at the surrounding joint to thrive. Excess load on cartilage will impede its health, as will inactivity [xiii]. Obesity mixed with inactivity and low skeletal muscle mass, coupled with poor diet and impaired blood sugar handling is a recipe for arthritis. Collagen deposition and linear remodeling relies on forces across a joint in the proper vectors for optimal strength and integrity of ligaments and tendons [xiv]. Challenging a joint through normal range of motion in strength training puts a stressor on the enthesis, thereby promoting proper remodeling and integrity where these structures intermingle into bone.
These are all factors to be considered for tissue optimization in patients undergoing any stem cell procedure. One’s stem cells are only as good as one’s cellular milieu.
i. Hankenson, et al. Omega-3 Fatty Acids Enhance Ligament Fibroblast Collagen Formation in Association with Changes in Interleukin-6 Production. Proceedings of the Society for Experimental Biology and Medicine. Volume 223, Issue 1, pages 88-95, January 2000
ii. Oreffo, et al. Maternal protein deficiency affects mesenchymal stem cell activity in the developing offspring. Bone , Volume 33 , Issue 1, 100-107
iii. Benito-Ruiz, et al. International Journal of Food Sciences and Nutrition.Volume 60, Supplement 2, 2009
iv. B Peterkofsky. Ascorbate requirement for hydroxylation and secretion of procollagen: relationship to inhibition of collagen synthesis in scurvy. Am J Clin Nutr December 1991. vol. 54 no. 6 1135S-1140S
v. Geerlings, Hoepelman. Immune dysfunction in patients with diabetes mellitus (DM). FEMS Immunology and Medical Microbiology 26 (1999):259-265.
vi. Fadini, et al. Glucose tolerance is negatively associated with circulating progenitor cell levels. Diabetologia. October 2007, Volume 50, Issue 10, pp 2156-2163
vii. Craig, et al. Effects of progressive resistance training on growth hormone and testosterone levels in young and elderly subjects. Mech Ageing Dev. 1989 Aug;49(2):159-69.
viii. Hansen S, et al. The effect of short-term strength training on human skeletal muscle: the importance of physiologically elevated hormone levels. Scandinavian Journal of Medicine & Science in Sports, 2001; 11: 347-354.
ix. Balakrishnan VS, Rao M, Menon V, et al. Resistance Training Increases Muscle Mitochondrial Biogenesis in Patients with Chronic Kidney Disease.Clinical Journal of the American Society of Nephrology : CJASN. 2010;5(6):996-1002.
x. Hawke, Thomas J. Muscle Stem Cells and Exercise Training. Exercise & Sport Sciences.Reviews: April 2005 – Volume 33 – Issue 2 – pp 63-68.
xii. Fulton T. et al. Exercise reverses ethanol inhibition of neural stem cell proliferation. Alcohol. Volume 33, Issue 1, May 2004, Pages 63-71.
xiii. Isaksson, et al. Physical Exercise Improves Properties of Bone and Its Collagen Network in Growing and Maturing Mice. Calcif Tissue Int (2009) 85:247-256 DOI 10.1007/s00223-009-9273-3.
xiv. Fox, et al. The Basic Science of Articular Cartilage: Structure, Composition, and Function. Sports Health. 2009 Nov; 1(6): 461-468. doi: 10.1177/1941738109350438.
xv. Ravin. The Use of Testosterone and Growth Hormone for Prolotherapy. Journal of Prolotherapy. Vol 2, Issue 4, Nov 2010: 495-503
xvi. Liao, et al. Testosterone replacement therapy can increase circulating endothelial progenitor cell number in men with late onset hypogonadism. Andrology. 2013 Jul;1(4):563-9. doi: 10.1111/j.2047-2927.2013.00086.x. Epub 2013 May 8.
xvii. Chen, et al. Testosterone replacement therapy promotes angiogenesis after acute myocardial infarction by enhancing expression of cytokines HIF-1a, SDF-1a and VEGF. Eur J Pharmacol. 2012 Jun 5;684(1-3):116-24. doi: 10.1016/j.ejphar.2012.03.032. Epub 2012 Mar 30.
xviii. Fimmel S, et al. Influence of physiological androgen levels on wound healing and immune status in men. Aging Male. 2005;8:166-174.
xix. Gilliver SC, et al. Androgens modulate the inflammatory response during acute wound healing. J. Cell Sci. 2006;119:722- 732.
xx. Joshua D. Safer,Thyroid Hormone and Wound Healing. Journal of Thyroid Research, vol. 2013, Article ID 124538, 5 pages, 2013. doi:10.1155/2013/124538
xxi. G. F. Lemkine. Adult neural stem cell cycling in vivo requires thyroid hormone and its alpha receptor. The FASEB Journal. Vol. 19 no. 7 863-865. February 23, 2005, doi:10.1096/fj.04-2916fje.
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