Stem Cell Activation: Supplement Cocktail and Photobiomodulation

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After watching a video explaining stem cell activation (for more information on stem cells, check out this post) through oral supplementation on December 2016, I proceeded to get all the relevant ingredients listed in the commercialized product. I got blueberry extract powder, green tea capsules, leucine powder, L-carnosine tablets, and vitamin D3 capsules. I started taking those every day, noticing a higher attention span and increased energy levels in days of high stress.

Prior to that, I was taking vitamin C powder for adrenal support and stress relief, glycine powder for tissue regeneration and glyphosate protection (it is also a very convenient sweetener) and spirulina powder for general heavy metal relief. To make things simpler, I decided to mix all the powders of the stem cell activation with my vitamin C, glycine and spirulina powders in one single cocktail. To my surprise, the spirulina tasted much better that way. I took the cocktail with the green tea capsules and the L-carnosine. I didn’t do the vitamin D3 since my levels were okay.

After reading Cracking the Stem Cell Code: What’s New, What’s Real & What’s next in Stem Cell Science, I decided to include some capsules of Aphanizomenon Flos aquae(AFA) extract into the cocktail of supplements. Then, after learning the details of photobiomodulation and its potential to active stem cells, I included that into the protocol.

Let’s have a closer look to the preliminary research behind this stem cell activation protocol.

Spirulina Promotes Stem Cell Genesis and Protects against LPS Induced Declines in Neural Stem Cell Proliferation

Adult stem cells are present in many tissues including, skin, muscle, adipose, bone marrow, and in the brain. Neuroinflammation has been shown to be a potent negative regulator of stem cell and progenitor cell proliferation in the neurogenic regions of the brain. Recently we demonstrated that decreasing a key neuroinflammatory cytokine IL-1b in the hippocampus of aged rats reversed the age-related cognitive decline and increased neurogenesis in the age rats. We also have found that nutraceuticals have the potential to reduce neuroinflammation, and decrease oxidative stress. The objectives of this study were to determine if spirulina could protect the proliferative potential of hippocampal neural progenitor cells from an acute systemic inflammatory insult of lipopolysaccharide (LPS). To this end, young rats were fed for 30 days a control diet or a diet supplemented with 0.1% spirulina. On day 28 the rats were given a single i.p. injection of LPS (1 mg/kg). The following day the rats were injected with BrdU (50 mg/kg b.i.d. i.p.) and were sacrificed 24 hours after the first injection of BrdU. Quantification of the BrdU positive cells in the subgranular zone of the dentate gyrus demonstrated a decrease in proliferationof the stem/progenitor cells in the hippocampus as a result of the LPS insult. Furthermore, the diet supplemented with spirulina was able to negate the LPS induced decrease in stem/progenitor cell proliferation. In a second set of studies weexamined the effects of spirulina either alone or in combination with a proprietary formulation (NT-020) of blueberry, green tea, vitamin D3 and carnosine on the function of bone marrow and CD34+ cells in vitro. Spirulina had small effects on its own and more than additive effects in combination with NT-020 to promote mitochondrial respiration and/or proliferation of these cells in culture. When examined on neural stem cells in culture spirulina increased proliferation at baseline and protected against the negative influence of TNFa to reduce neural stemcell proliferation. These results support the hypothesis that a diet enriched with spirulina and other nutraceuticals may help protect the stem/progenitor cells from insults.

They discuss how inflammation in the brain acts negatively on its stem cells. They studied several nutraceuticals including spirulina, blueberry extract, green tea, vitamin D3 and carnosine. They noticed that spirulina had a positive effect in protecting stem cells, but in combination with green tea, vitamin D3 and carnosine, it worked much better.

Nutraceuticals Synergistically Promote Proliferation of Human Stem Cells

A viable alternative to stem cell transplantation is to design approaches that stimulate endogenous stem cells to promote healing and regenerative medicine. Many natural compounds have been shown to promote healing; however, the effects of these compounds on stem cells have not been investigated. We report here the effects of several natural compounds on the proliferation of human bone marrow and human CD34 and CD133 cells. A dose-related effect of blueberry, green tea, catechin, carnosine, and vitamin D3 was observed on proliferation with human bone marrow as compared with human granulocyte-macrophage colony-stimulating factor (hGM-CSF). We further show that combinations of nutrients produce a synergistic effect to promote proliferation of human hematopoietic progenitors. This demonstrates that nutrients can act to promote healing via an interaction with stem cell populations.

This research is focused on enhancing the body’s own production of stem cells to promote healing. They studied the components of the stem cell cocktail that we are concerned with.  Let’s see what the authors have to say about the relevant ingredients:

Recent laboratory studies demonstrate that vitamin D3 has a dramatic effect on stimulating the proliferation of various forms of multipotent progenitor cells, particularly those involved with the immune system (14). Research on cellular senescence (the end of the life cycle of dividing cells) suggests that the dietary nutrient carnosine, found in muscle and brain of mammals, has the remarkable ability to rejuvenate cells approaching senescence, restoring normal appearance and extending cellular life span (15,16). Still other studies suggest dietary supplementation with foods high in antioxidants, such as blueberries, can prevent and even reverse cellular and behavioral parameters that decline as a function of aging (17,18). For example, dietary supplementation with 2% blueberry extract has produced both neuroprotective and neurorestorative effects in aged animals, perhaps as a result of modulation of cell signaling cascades (19). Furthermore, blueberry extract has been shown to increase neurogenesis in the aged rat brain (20). Green tea is a drink made from the steamed and dried leaves of the Camellia sinensis plant, a shrub native to Asia. Green tea has been widely consumed in Japan, China, and other Asian nations to promote good health for at least 3,000 years. Recently, scientists have begun to study its health effects in animal, laboratory, and observational human studies. Although active compounds within green tea extract have been shown to inhibit the growth of a number of tumor cell lines, they do not affect the growth of normal cells at similar concentrations (21,22) and actually may provide cellular protection from aging (23).

 Now let’s see what research has to say about one of my favorite supplements.

Leukaemia: Vitamin C regulates stem cells and cancer

It emerges that high levels of vitamin C in blood-forming stem cells influence the number and function of the cells and affect the development of leukaemia, through binding to a tumour-suppressor protein, Tet2.

The substrates, intermediates and products of cellular metabolism have the potential to influence cellular identity and transformation to cancer1,2. Two papers (one by Agathocleous et al.3 online in Nature and the other by Cimmino et al.4 in Cell) now find a previously unknown role for one such metabolite, vitamin C, in stem-cell biology. They show that levels of vitamin C, also known as ascorbate, regulate the number and function of blood-forming haematopoietic stem cells, largely through effects on the Tet2 protein. This change, in turn, alters the progression of leukaemia.

Researchers’ ability to profile metabolites in stem cells has previously been limited by the fact that such analyses typically require millions of cells. Mouse blood cells, for instance, consist of less than 0.01% haematopoietic stem cells (HSCs)5, making it difficult to obtain sufficient numbers for study. Agatho­cleous et al. overcame this problem by develop­ing a method for analysing metabolites in as few as 10,000 cells. Using this technique, they found clear differences between the metabolic profiles of mouse blood cells at various stages of differentiation.

The authors discovered that levels of vitamin C are between 2 and 20 times higher in populations of immature stem cells and progenitor cells than in more-differenti­ated cell types. Consistent with this finding, they showed that expression of the gene Slc23a2, which encodes a protein that imports vitamin C, was higher in HSCs than in more-differentiated cells. Importantly, the researchers confirmed their observations in human blood cells.

Transcription factors and signaling molecules are well-known regulators of stem cell identity and behavior; however, increasing evidence indicates that environmental cues contribute to this complex network of stimuli, acting as crucial determinants of stem cell fate. l-Ascorbic acid (vitamin C (VitC)) has gained growing interest for its multiple functions and mechanisms of action, contributing to the homeostasis of normal tissues and organs as well as to tissue regeneration. Here, we review the main functions of VitC and its effects on stem cells, focusing on its activity as cofactor of Fe+2/αKG dioxygenases, which regulate the epigenetic signatures, the redox status, and the extracellular matrix (ECM) composition, depending on the enzymes’ subcellular localization. Acting as cofactor of collagen prolyl hydroxylases in the endoplasmic reticulum, VitC regulates ECM/collagen homeostasis and plays a key role in the differentiation of mesenchymal stem cells towards osteoblasts, chondrocytes, and tendons. In the nucleus, VitC enhances the activity of DNA and histone demethylases, improving somatic cell reprogramming and pushing embryonic stem cell towards the naive pluripotent state. The broad spectrum of actions of VitC highlights its relevance for stem cell biology in both physiology and disease.

I mentioned above the book Cracking the Stem Cell Code by Christian Drapeau where he also talks about some of the nutrients in our stem cell activation cocktail. Drapeau reports in his book:

It was reported that antioxidants exracted from berries and other sources can support the proliferation of stem cells in vitro. In brief, a blend of blueberry, green tea, catechin, carnosine, and vitamin D3 increased by 70% the proliferation of bone marrow stem cells in vitro, as measured by a mitochondrial assay. In biology, many effects seen in a test tube do not mean anything in the body. Furthermore, given the ability of stem cells to proliferate through up to 20-50 generations after migrating in a tissue, which means that one stem cell will divide and lead to the formation of several thousand new cells, an increase of 70% may be of little physiological relevance. Nevertheless, these observations bring further support to the idea that diet and lifestyle are bound to affect stem cell physiology.

Probably the most interesting discovery in this field of stem cell nutrition, which has given rise to the concept of stem cell enhancers, pertains to the effect of an aquatic botanical called Aphanizomenon flos-aquae (AFA) on stem cell mobilization. AFA is a cyanophyta (blue-green algae, also referred to a cyanobacteria) that was recently shown to contain an L-selectin ligand that acts as a mild mobilizer of bone marrow stem cells.  Consumption of 1 gram of a patented AFA extract was shown to increase the number of circulating stem cells by an average of 25%, which is the equivalent of approximately 3 million new stem cells in the blood-stream.

 Which is why I decided to include AFA in the cocktail of supplements. The following study hints to its benefits:

Consequences of AphanizomenonFlos-aquae(AFA) extract (StemtechTM) on metabolic profile of patients with type 2 diabetes

Blue- green algae is one of the most nutrient dense foods which is rich in substances that have useful effects on human health. The purpose of this study was to evaluate the effectiveness of a water- soluble extract of the cyanophyta Aphanizomenon Flos-aquae (StemtechTM) as a functional supplement on CD markers, lipid profile, glucose levels as well as its side effects in Iranian patients with type 2 diabetes.

During this randomized, double-blind, placebo-controlled trial 49 type 2 diabetic patients, aged between 20 and 60 years with a HbA1C ≥ 7.5 %, were allocated. Patients were divided into two groups of placebo and treated with an equal ratio 1:1. The subjects in StemtechTM group received one capsule of StemFlo (508 mg) before breakfast and two capsules of StemEnhance (500 mg) after each meal for a period of 12 weeks, and placebo group was instructed to take placebo with the same pattern. During the intervention period, subjects were asked to keep usual diet and prohibited to take any functional foods or dietary supplements. Metabolic panel has been measured as the primary outcome of study at the beginning and end of the intervention period via blood sampling.
StemtechTM supplementation for 12 weeks decreased fasting blood glucose (FBG) and Glycated hemoglobin (HbA1c)

Not to bad for an off-the-counter green supplement.

As for glycine, the research is still open on that one. There is preliminary research to suggest that is positive:

Scientists reverse aging in human cell lines and give theory of aging a new lease of life

…the aging process in the mitochondrion is controlled by epigenetic regulation, not by mutations.

The researchers then looked for genes that might be controlled epigenetically resulting in these age-associated mitochondrial defects. Two genes that regulate glycine production in mitochondria, CGAT and SHMT2, were found. The researchers showed that by changing the regulation of these genes, they could induce defects or restore mitochondrial function in the fibroblast cell lines. In a compelling finding, the addition of glycine for 10 days to the culture medium of the 97 year old fibroblast cell line restored its respiratory function. This suggests that glycine treatment can reverse the age-associated respiration defects in the elderly human fibroblasts.

These findings reveal that, contrary to the mitochondrial theory of aging, epigenetic regulation controls age-associated respiration defects in human fibroblast cell lines. Can epigenetic regulation also control aging in humans? That theory remains to be tested, and if proven, could result in glycine supplements giving our older population a new lease of life.

 

In regards to leucine, it seems it is used because it promotes the proliferation and differentiation of stem cells in muscles. By activating protein synthesis in skeletal muscle, leucine promotes lean body mass which in itself is correlated with longevity and metabolic health. Here is more information about it:

Leucine Promotes Proliferation and Differentiation of Primary Preterm Rat Satellite Cells in Part through mTORC1 Signaling Pathway

As I mentioned above, it is preliminary research. I use the cocktail on challenging situations to promote healing. It doesn’t taste bad, more like a green blueberry lemonade if that makes any sense. The recipe is open for improvement according to experience and research.
 

 

As for the photobiomodulation part, I’ll make a brief summary afterwards. There is simply too much information on the subject, but there are basic principles to highlight before embarking on the magic of light therapy.

Update (October 8, 2017): The post is now available – Photobiomodulation and Stem Cell Activation

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Comments

  1. Jurian  September 26, 2017

    “A dose-related effect of blueberry, green tea, catechin, carnosine, and vitamin D3 was observed on proliferation with human bone marrow”

    Catechins and green tea extract are the same, right ?

    reply
  2. Ashu  September 27, 2017

    Thanks for the great article Gaby! Can this work with chlorella instead of spirulina? As I have loads of it!

    reply
    • Gabriela Segura, MD  September 27, 2017

      Don’t waste anything!;)

      reply
      • Richard  October 2, 2017

        Amazing empirical studies!
        A pharmacist consults with me regularly at VA…
        What she finds to be amazing is the the molecular relationship with glucose and vitamin C.
        I megadose irregularly with 5G (5000 mg) of vitamin C, and my blood glucose readings will be high, although I’m doing some healing a some level, and maybe even fasting.
        Ascorbate molecules and glucose are so similar that cells mistake one for the other…good news!
        This phenomena accelerates healing at the cellular level, and enhances introduction of other healing substances.

      • Gabriela Segura, MD  October 2, 2017

        I love vitamin C!

  3. Bahar  September 27, 2017

    Many thanks, I’m gonna try this out! I have two questions:

    – What is the reason behind adding Leucine powder to the mix? From the description of the supplement, I’ve read it may be handy for people who exercise and it also helps using fat for energy. I’d like to add that as well.
    – Since one of the papers above mention that participants took AFA after their meal, would you recommend to drink the cocktail on a full stomach or do you think it won’t matter that much?

    Thanks again!

    reply
    • Gabriela Segura, MD  September 28, 2017

      Good catch! Leucine was part of the original commercialized formula. I think it is used because leucine promotes the proliferation and differentiation of stem cells in muscles. By activating protein synthesis in skeletal muscle, it promotes lean body mass which in itself is correlated with longevity and metabolic health. Here is more information about it (will incorporate it to the article):

      Leucine Promotes Proliferation and Differentiation of Primary Preterm Rat Satellite Cells in Part through mTORC1 Signaling Pathway

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4446757/

      I usually take the cocktail after a meal, although I don’t think it matters much.

      Hope you like it!

      reply

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