Stem Cell Supplements

By Chris Centeno, MD /

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stem cell supplements

If you search online for stem cell supplements, you’re bound to find a long list. Figuring out what to make of all of these supplements can be pretty daunting, as each claims to be the best and greatest. Hence, I thought I would perform a deep dive into how various supplements and plant extracts impact stem cells.

The Supplement Game

You need to be careful with supplements and health claims and especially stem cell supplements. Why? Generally, the process of creating a new supplement is pretty simple. You go online, find some studies that seem to fit what you’re looking for, create a master file, choose your ingredients, and you’re off. Meaning, no original lab or clinical research is performed.

For example, to create a stem cell supplement, you could focus on the different ways that stem cells get impacted by supplement ingredients, like proliferation. This means that the substance helps stem cells make more of themselves. You then choose from some the ingredients below and you’ve got a new supplement. However, is this really what’s desired? Do you want more stem cells? Is that a good thing or a bad thing? What other impacts do these supplements have on stem cells? All of this is largely unknown.

Specific Supplements

Here I’ll start with a few common supplements you might see on the grocery store shelf, to see what the research says about how they impact stem cells. Realize that many of the research studies that can be found on this topic may use a different stem cell type. Hence, I tried to focus mostly on mesenchymal stem cells.

There are Different Stem Cell Types?

You’ve probably heard about embryonic stem cells (ESCs). These are derived from an embryo and controversial. None of the research on stem cell supplements reviewed here used ESCs. Then there are adult stem cells that live in your body and act as the repairmen. These come in many flavors, but the type I have focused on in this review are called mesenchymal stem cells (MSCs), the triathlete of adult stem cells. They can both direct tissue repair like a general contractor and also differentiate (turn into) many different cell types like bone, cartilage, muscles, tendon, etc… These cells also have subtypes that come from various tissues like bone marrow, fat, or elsewhere. While similar, these different MSC types are not the same.

Glucosamine/Chondroitin

These two supplements are commonly used in arthritis treatments and are often derived from shellfish. Hence it makes sense that glucosamine can promote MSCs to become cartilage and inhibit the breakdown of cartilage. Chondroitin can also enhance the ability of MSCs to turn into cartilage (26, 27).

Chondroitin also has real measurable effects on knee cartilage in actual patients. In one study, it reduced cartilage volume loss on MRI after 6 months (28). Glucosamine also seemed to help cartilage quality when measured on a specialized MRI (29). In another study, glucosamine reduced cartilage breakdown products (30). Finally, when compared to prescription Celebrex, the combination of glucosamine and chondroitin were better at improving function and reducing cartilage breakdown in the knee (31).

Curcumin/Turmeric

The most commonly promoted anti-inflammatory supplements right now are curcumin and turmeric. Turmeric and curcumin are derived from the turmeric root with turmeric being the spice you know from Indian cooking, and curcumin one of  the chemical compounds known as curcuminoids, which are believed to be biologically active. In addition, in order for curcumin to be absorbed in the gut, a black pepper extract is commonly required.

In one study that used adipose MSCs to treat heart attacks, curcumin improved the viability of the cells, reduced scarring in the heart muscle being repaired, and promoted new blood vessel formation (1). In another involving bone marrow MSCs, curcumin improved bone formation (2).

The curcuminoids also impact arthritis through anti-inflammatory pathways, down-regulating enzymes such as phospholipase A2, cyclooxygenase-2, and lipoxygenases, and reducing inflammatory cytokines like TNF-alpha-and interleukin-1β (IL-1β), IL-6, and IL-8 (19). All of these effects have translated into real measurable impacts on patients with knee arthritis (20, 23,24). In other studies, Curcumin has been shown to be as effective as common NSAID anti-inflammatories such as Diclofenac and Ibuprofen (21,22).

A Look at Many Supplements and How They Influence Stem Cell Differentiation

supplements for stem cells

The image to the left is from a review article that looked at how many different supplements and plant extracts changed how stem cells turned into other cell types (differentiation) (3). For example, curcumin pushed stem cells towards making more stem cells (proliferation) and toward muscle cells. Quercetin pushed stem cells toward making bone. Flavinoids like quercitin and others found in teas, cocoa, grapes, apples, etc… helped stem cells become cartilage. The traditional Chinese herb Shen-Nong (Fructus Ligustri Lucidi) also helped stem cell turn into bone across several studies (17,18).

More on Stem Cell Proliferation

Proliferation means getting cells to make more of themselves or promoting MSC growth. If you want stem cells to repair something, then this could be good. On the other hand, if you have cancer, then this is one mechanism by which stem cells can make tumors bigger, so proliferation can be a two-edged sword.

Licorice root increased proliferation in bone marrow stem cells (4). Other supplements and natural plant-based extracts that increased stem cell proliferation include Ginko BilobaFerula gummosa (a Persian plant that produces an aromatic gum resin), apple extract, Cissus quadrangularis (Veld Grape-an Ayurvedic medicine), fennel (Foeniculum vulgare), Gu Sui Bu (Chinese medicine herb aka Rhizoma drynariae), spiked thyme (Thymbra spicata), Guarana, basil (Ocimum basilicum), soy, and Barrenwort (Epimedium pubescens) (5-16).

Making Sense of All of this Research

The problem with looking at these studies and throwing a bunch of ingredients into a supplement is that you have no idea of how these ingredients will interact. In addition, many of these studies are performed with different stem cell subtypes in differing conditions. For example, some used a 3D culture environment and some more traditional culture. Some added other things into the petri dish in addition to the supplement or plant extract. Hence, if you want a real stem cell supplement, you really need to do the lab research yourself.

Making a Stem Cell Supplement by Spending a Year in the Lab

When we sat down to try to create a stem cell supplement, I had looked at all of the above research at the time (many of these studies didn’t exist back then) and picked out candidate ingredients. However, for our purposes, we wanted a supplement mix with the following properties:

  • Anti-inflammatory
  • Chondrogenic
  • Proliferative
  • Protective against inflammatory bad guys

Meaning, we wanted a stem cell supplement that by itself had ingredients that could fight inflammation. Why? Inflammation can cause cartilage breakdown and arthritis and produces abnormal cartilage cells. In addition, the average American is loaded with way too much inflammation, so tamping that down will also make patients feel better.

Chondrogenic means cartilage producing. We wanted a stem cell supplement that could promote MSCs to turn into cartilage cells as most of our patients had arthritis. However, doing that required lab testing of various supplements in culture with bone marrow MSCs. This required weeks to months for each lab test, carefully measuring the amounts of cartilage produced using fluorescent microscopy.

We wanted a supplement that would cause stem cells to grow in culture, as many of our patients were older and we wanted to give their stem cells a boost. This again meant testing these supplements with human bone marrow MSCs in culture.

Finally, we wanted stem cell supplement ingredients that could protect the cells against bad inflammatory chemicals. Why? These live inside the joints of our patients with arthritis. So blocking the impact of those bad guys on the cells we injected was critical.

Watch my video below for more information:

stem cell support formulaSo what did all of this testing produce? The world’s first stem cell support formula that was actually lab-tested on the cells we were using and in the conditions we wanted to replicate. There is simply nothing else like it out there. Click here for more information.

The upshot? There’s quite a bit of research now on how various supplements and plant extracts impact stem cells. However, as you can see, it’s a bit all over the map. Hence, if you want stem cell supplements that do certain things, you really need to do the lab testing yourself!

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References:

(1) Liu J, Zhu P, Song P, Xiong W, Chen H, Peng W, Wang S, Li S, Fu Z, Wang Y, Wang H. Pretreatment of adipose derived stem cells with curcumin facilitates myocardial recovery via antiapoptosis and angiogenesis. Stem Cells Int. 2015;2015:638153. doi: 10.1155/2015/638153

(2) Gu Q, Cai Y, Huang C, Shi Q, Yang H. Curcumin increases rat mesenchymal stem cell osteoblast differentiation but inhibits adipocyte differentiation. Pharmacogn Mag. 2012;8:202–208. doi: 10.4103/0973-1296.99285.

(3) Saud B, Malla R, Shrestha K. A Review on the Effect of Plant Extract on Mesenchymal Stem Cell Proliferation and Differentiation. Stem Cells Int. 2019;2019:7513404. Published 2019 Jul 24. doi:10.1155/2019/7513404

(4) Azizsoltani A., Piri K., Behzad S., et al. Ethyl acetate extract of licorice root (Glycyrrhiza glabra) enhances proliferation and osteogenic differentiation of human bone marrow mesenchymal stem cells. Iranian Journal of Pharmaceutical Research: IJPR2018;17(3):1057–1067. https://www.ncbi.nlm.nih.gov/pubmed/30127828

(5) Gu Q., Chen C., Zhang Z., et al. Ginkgo biloba extract promotes osteogenic differentiation of human bone marrow mesenchymal stem cells in a pathway involving Wnt/β-catenin signaling. Pharmacol. Res2015;97:70–78. doi: 10.1016/j.phrs.2015.04.004.

(6) Mahmoudi Z., Soleimani M., Saidi A., Iranshahi M., Azizsoltanli A. Effect of Ferula gummosa ethanolic extract on osteogenesis in human mesenchymal stem cells. Journal of Medicinal Plants2013;2(46):50–59. 

(7) Lee J., Shin M. S., Kim M. O., et al. Apple ethanol extract promotes proliferation of human adult stem cells, which involves the regenerative potential of stem cells. Nutrition Research. 2016;36(9):925–936. doi: 10.1016/j.nutres.2016.06.010.

(8) Potu B. K., Bhat K. M. R., Rao M. S., et al. Petroleum ether extract of Cissus quadrangularis (Linn.) enhances bone marrow mesenchymal stem cell proliferation and facilitates osteoblastogenesis. Clinics2009;64(10):993–998. doi: 10.1590/S1807-59322009001000010.

(9) Mahmoudi Z., Soleimani M., Saidi A., Khamisipour G., Azizsoltani A. Effects of Foeniculum vulgare ethanol extract on osteogenesis in human mecenchymal stem cells. Avicenna Journal of Phytomedicine2013;3(2):135–142. https://www.ncbi.nlm.nih.gov/pubmed/25050267

(10) Peng-Zhang, Dai K.-r., Yan S.-g., et al. Effects of naringin on the proliferation and osteogenic differentiation of human bone mesenchymal stem cell. European Journal of Pharmacology2009;607(1-3):1–5. doi: 10.1016/j.ejphar.2009.01.035.

(11) Mendi A., Yağcı B. G., Kızıloğlu M., et al. Thymbra spicata var. intricata induces mesenchymal stem cell proliferation and osteogenic differentiation. Brazilian Archives of Biology and Technology2017;60 doi: 10.1590/1678-4324-2017160391.

(12) Machado A. K., Cadoná F. C., Azzolin V. F., et al. Guaraná (Paullinia cupana) improves the proliferation and oxidative metabolism of senescent adipocyte stem cells derived from human lipoaspirates. Food Research International. 2015;67:426–433. doi: 10.1016/j.foodres.2014.11.056.

(13) Mendi A. H., Gökçınar Yağcı B., Sarac N., Kızıloğlu M., Yılmaz D., Uçkan D. Effect of Ocimum basilicum on mesenchymal stem cell proliferation and differentiation: does the effect change according to niches? International Journal of Secondary Metabolite2017;4(3):1–10. doi: 10.21448/ijsm.356244.

(15) Lee J., Roh K. B., Kim S. C., Lee J., Park D. Soy peptide-induced stem cell proliferation: involvement of ERK and TGF-β1. The Journal of Nutritional Biochemistry2012;23(10):1341–1351. doi: 10.1016/j.jnutbio.2011.08.003.

(16) Yin X.-x., Chen Z.-q., Liu Z.-j., Ma Q.-j., Dang G.-t. Icariine stimulates proliferation and differentiation of human osteoblasts by increasing production of bone morphogenetic protein 2. Chinese Medical Journal2007;120(3):204–210. doi: 10.1097/00029330-200702010-00006.

(17) Li G., Zhang X. A., Zhang J. F., et al. Ethanol extract of Fructus Ligustri Lucidi promotes osteogenesis of mesenchymal stem cells. Phytotherapy Research. 2009;24(4):571–576. doi: 10.1002/ptr.2987.

(18) Ko C., Siu W., Lau C., Lau C. B., Fung K., Leung P. Osteoprotective effects of Fructus Ligustri Lucidi aqueous extract in aged ovariectomized rats. Chinese Medicine2010;5(1):p. 39. doi: 10.1186/1749-8546-5-39.

(19) Akuri MC, Barbalho SM, Val RM, Guiguer EL. Reflections about Osteoarthritis and Curcuma longaPharmacogn Rev. 2017;11(21):8–12. doi:10.4103/phrev.phrev_54_16

(20) Henrotin Y, Malaise M, Wittoek R, et al. Bio-optimized Curcuma longa extract is efficient on knee osteoarthritis pain: a double-blind multicenter randomized placebo controlled three-arm study. Arthritis Res Ther. 2019;21(1):179. Published 2019 Jul 27. doi:10.1186/s13075-019-1960-5

(21) Shep D, Khanwelkar C, Gade P, Karad S. Safety and efficacy of curcumin versus diclofenac in knee osteoarthritis: a randomized open-label parallel-arm study. Trials. 2019;20(1):214. Published 2019 Apr 11. doi:10.1186/s13063-019-3327-2

(22) Kuptniratsaikul V, Dajpratham P, Taechaarpornkul W, et al. Efficacy and safety of Curcuma domestica extracts compared with ibuprofen in patients with knee osteoarthritis: a multicenter study. Clin Interv Aging. 2014;9:451–458. Published 2014 Mar 20. doi:10.2147/CIA.S58535

(23) Panahi Y, Rahimnia AR, Sharafi M, Alishiri G, Saburi A, Sahebkar A. Curcuminoid treatment for knee osteoarthritis: a randomized double-blind placebo-controlled trial. Phytother Res. 2014 Nov;28(11):1625-31. doi: 10.1002/ptr.5174.

(24) Rahimnia AR, Panahi Y, Alishiri G, Sharafi M, Sahebkar A. Impact of Supplementation with Curcuminoids on Systemic Inflammation in Patients with Knee Osteoarthritis: Findings from a Randomized Double-Blind Placebo-Controlled Trial. Drug Res (Stuttg). 2015 Oct;65(10):521-5. doi: 10.1055/s-0034-1384536.

(25) Derfoul A, Miyoshi AD, Freeman DE, Tuan RS. Glucosamine promotes chondrogenic phenotype in both chondrocytes and mesenchymal stem cells and inhibits MMP-13 expression and matrix degradation. Osteoarthritis Cartilage. 2007 Jun;15(6):646-55. https://www.ncbi.nlm.nih.gov/pubmed/17337215

(26) Wang T, Yang F. A comparative study of chondroitin sulfate and heparan sulfate for directing three-dimensional chondrogenesis of mesenchymal stem cells. Stem Cell Res Ther. 2017;8(1):284. Published 2017 Dec 19. doi:10.1186/s13287-017-0728-6

(27) Goude MC, McDevitt TC, Temenoff JS. Chondroitin sulfate microparticles modulate transforming growth factor-β1-induced chondrogenesis of human mesenchymal stem cell spheroids. Cells Tissues Organs. 2014;199(2-3):117–130. doi:10.1159/000365966

(28) Wildi LM, Raynauld JP, Martel-Pelletier J, et al. Chondroitin sulphate reduces both cartilage volume loss and bone marrow lesions in knee osteoarthritis patients starting as early as 6 months after initiation of therapy: a randomised, double-blind, placebo-controlled pilot study using MRI. Ann Rheum Dis. 2011;70(6):982–989. doi:10.1136/ard.2010.140848

(29) Martí-Bonmatí L, Sanz-Requena R, Rodrigo JL, Alberich-Bayarri A, Carot JM. Glucosamine sulfate effect on the degenerated patellar cartilage: preliminary findings by pharmacokinetic magnetic resonance modeling. Eur Radiol. 2009 Jun;19(6):1512-8. doi: 10.1007/s00330-008-1286-1.

(30) Petersen SG, Saxne T, Heinegard D, Hansen M, Holm L, Koskinen S, Stordal C, Christensen H, Aagaard P, Kjaer M. Glucosamine but not ibuprofen alters cartilage turnover in osteoarthritis patients in response to physical training. Osteoarthritis Cartilage. 2010 Jan;18(1):34-40. doi: 10.1016/j.joca.2009.07.004.

(31) Zeng C, Wei J, Li H, et al. Effectiveness and safety of Glucosamine, chondroitin, the two in combination, or celecoxib in the treatment of osteoarthritis of the knee. Sci Rep. 2015;5:16827. Published 2015 Nov 18. doi:10.1038/srep16827

Category: Supplements

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2 thoughts on “Stem Cell Supplements

  1. Stanley G.

    Thanks Dr. Centeno. Question: do these supplements (Glucosamine/chondroiten, curcumin/tumeric) also help with and combat arthritis and cartilage breakdown in areas other than just the knees? It seems like a lot of this research is focused on knees and I’d like to know if these help in other areas too.

    1. Regenexx Team

      Hi Stanley,
      Because supplements are taken orally, the effects they produce in the body would not be specific to one particular joint.

Chris Centeno, MD

Regenexx Founder

Chris Centeno, MD is a specialist in regenerative medicine and the new field of Interventional Orthopedics. Centeno pioneered orthopedic stem cell procedures in 2005 and is responsible for a large amount of the published research on stem cell use for orthopedic applications.
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