Stem Cell Nutritional Research

Stem Cell Nutritional Research


One of the most exciting scientific frontiers is the study of human stem cells. Stem cells are found in various organs throughout the body including bone marrow, blood, the brain and the umbilical cord. They can differentiate into other cells, and they act as a repair system for the damaged cells in our body. Without adequate healthy stem cells our body cannot repair other cells as needed and this can lead to various conditions or diseases. Given their unique regenerative abilities, stem cells offer new potentials for treating health concerns.

Currently stem cells are being transplanted via bone marrow to help those with leukemia and other blood borne cancers. But, more simple solutions are being sought after and therefore natural compounds, like those discussed below, are being studied for their effects on the proliferation and protection of adult stem cells.

1. Nutraceuticals Synergistically Promote Proliferation of Human Stem Cells

Bickford P.C., Tan J., Shytle R.D., Sanberg C.D., El-Badri N., and Sanberg P.R. Stem Cells and Development. 2006; 15:118-123.

Conclusion: A positive dose dependent result on the proliferation of stem cells was found when blueberry, green tea, catechin, carnosine or vitamin D3 was added to the cells in vitro. The combination of these powders offered a synergistic effect and had even greater results on the stem cell proliferation.

Summary: Stem cells are currently under investigation because they are thought to have the ability to help promote healing and aid in the treatment of various diseases such as cancer, diabetes and Parkinson’s disease. They are currently used like transplanted tissue to treat these conditions. However, little has been done to enhance endogenous stem cells to promote healing.

Blueberry, green tea, catechin, carnosine and vitamin D3 are all natural substances that are thought to aid in the proliferation (“reproduction”) of stem cells. By enhancing the proliferation of stem cells a person could potentially live a healthier life by avoiding disease or improving existing conditions. In this study the substance previously described were tested in vitro with bone marrow, CD34+ and CD133+ cells (all of which are different types of stem cells). After the initial individual testing of each substance, they were each combined with the blueberry powder and tested. A combination of all of the powders was also examined. The results were compared to a positive control, meaning that the control was already known to aid in the proliferation of stem cells.

All of the individual substance had a dose dependent impact on the proliferation of the cells, meaning that the higher the dose was, the more the substance promoted cell proliferation. When the substances were combined with blueberry they all had even greater results. When tested with the CD34+ and CD133+ the combination of all of the substances had the greatest impact on cell proliferation. From this, the study was able to conclude that the natural compounds tested can promote the proliferation of stem cells in vitro and the combination of all of the substances had a synergistic effect.

2. Oxidative Stress of Neural, Hematopoietic, and Stem Cells: Protection by Natural Compounds

Shytle R.D., Ehrhart J., Tan J., et al. Rejuvenation Research. 2007; 10 (2): 173-178.

Conclusion: The blend of natural ingredients known as the base formula supplement was found to reduce oxidative stress-induced apoptosis both in vitro and in vivo.

Summary: The base formula blend has already been studied for its ability to proliferate stem cells, and now it is being tested for its ability to reduce oxidative stress-induced apoptosis (cell death). The previous study indicated that oxidative stress limits the stem cells ability to regenerate. As a person ages and their stem cells become more prone to oxidative stress their bodies don’t have the ability to heal itself as well anymore.

The base formula is a blend of blueberry extract, green tea extract, carnosine and vitamin D3. In the previous study these powders had a synergistic effect when promoting the proliferation of stem cells. In this study they tested the supplement powder in vitro and in vivo. In vitro, the supplement was found to reduce oxidative stress and lower total cell death. Each individual component of the neutraceutical formula was tested and showed a decrease in cell death, but the synergistic effect of the base formula combination showed a much greater decrease in cell death. This synergistic effect was also observed in vivo.

The in vivo study was done on mice and they were given either a “low” or “high” dose of the supplement. The results showed a dose-dependent decrease in cell death however, both doses were able to reduce oxidative stress on the cells. With these results the study was able to conclude that the base supplement blend has been shown to be able to defend against oxidative stress in vivo.

Doctors Note: Oxidative stress can be very harmful to the body. Oxidation occurs when electrons are stolen from cells, turning those cells into free radicals that then cause damage to other cells. This turns into a snowball effect, because the free radicals keep stealing electrons from cells to stabilize themselves but also creating more radicals in the process. When enough damage has been done, this chain of events can eventually lead to apoptosis or cell death. This damage may be linked to neurodegenerative and cardiovascular diseases.

Antioxidants are typically the first line of defense against oxidative stress. The antioxidants will donate one of their extra electrons to stop the long chain of destruction. However, sometimes the antioxidants are not naturally plentiful and must be supplemented. The supplement blend has been shown to be able to defend against oxidative stress.

3. Dietary Supplementation Exerts Neuroprotective Effects in Ischemic Stroke Model

Yasuhara T., Hara K., Maki M., et al. Rejuvenation Research. 2008; 11 (1): 201-214.

Conclusion: Supplementation with a natural ingredient blend, the supplement formula has been shown to have a neuroprotective effect when given prior to a stroke in an animal model.

Summary: Stroke is one of the leading causes of death, with a few expensive therapies for treatment. This lack of therapies for such a large population has warranted the research for finding new ways of alleviating the suffering of stroke victims. Currently caloric restriction or fasting has been shown to help alleviate symptoms related to stroke by increasing neurogenesis. Neurogenesis is the “birth of neurons” which more simply means the repair and growth of the brain. In this study it was assumed that the counterpart of caloric restriction, increasing the nutritive diet, could also be therapeutic and initiate neurogenesis. How a nutritive diet supplement could promote neurogenesis and benefit those who have suffered from a stroke was examined in this study.

Rats were given a supplement blend of blueberry, green tea, vitamin D3 and carnosine, together the blend is known as the base formula. The animals were supplemented with the base formula for two weeks, then underwent stroke surgery (inducing a stroke), and then given the supplement for two additional weeks after the stroke. Both the control and the treated groups suffered from neurological damage after the stroke. However, the group receiving the supplement formula had significantly less damage in both neurologic and motor tests as compared to the control group. The base formula treated rats also showed less damage done to the brain.

Oxidative stress can also cause damage to the brain. The substances found in the supplement formula blend are all known to have antioxidant capabilities. Overall the study found that the antioxidant power of the blend along with its ability for neurogenesis makes it very appealing as a neuroprotective agent.

Doctors Note: A stroke occurs when there is a lack of blood flow or blockage of blood flow to the brain. The lack of blood causes the brain to rapidly lose function. This can lead to neurological damage, complications and death. A stroke can end up being very debilitating, making a person go through intense therapies during rehabilitation, sometimes never fully recovering. High blood pressure, high cholesterol, diabetes, anticoagulation drugs, and nutrition are a few of the leading causes of a stroke.

Due to the severity of strokes, prevention and adequate rehabilitation is extremely important. Sometimes clearing up the clot or blockage can be as simple as taking certain medications and other times a person will have to get surgery to get rid of the clot. Since a person can lose brain function from a stroke, proper protection is very important. Currently the blend has shown to have neuroprotective effects if taken before a stroke. This is due to its neurogenesis abilities and the antioxidant properties of all of the components of the blend.

4. A Natural Therapeutic Approach to Optimize Spatial Memory Performance and Increase Neural Progenitor Cell Proliferation and Decrease Inflammation in the Aged Rat

Acosta S., Jernberg J., Sanberg C.D., et al. Rejuvenation Research. 2010; 13 (5): 581-588.

Conclusion: The base formula dietary supplement improved the proliferation of the progenitor cells and helps improve cognitive function in aging adults.

Summary: There is a large amount of evidence that demonstrates that as adults age, they lose cognitive function. The stem cells located in the brain, known as progenitor cells, cannot proliferate (reproduce) as well as they used to when one ages. This can impact a person’s stem cell environment in the brain and has a negative influence on the function of these cells.

Stem cells can differentiate into other cells and function as a repair system for the body. In turn, when the function of these cells becomes compromised there can potentially be negative side effects possibly resulting in a neurodegenerative disease. Also contributing to this effect is oxidative stress, pro-inflammatory cytokines (proteins that cause inflammation), and microglial (immune cells in the brain) activation, since these can increase as a person ages.

This study examined the effect that a blend of blueberry, green tea, vitamin D3 and carnosine powders, called the base formula, would have on the progenitor cells in aged rats. Aged rats were given the supplement for 3 weeks and were compared to control aged and young rats. The rat’s behavior and memory was tested via a Morris water maze (MWM). Along with this test the rats were also examined on a cellular level to determine the changes that occurred while being supplemented with the base formula.

It was found that the aged rats given the base formula had better result in the MWM, demonstrating that these rats had significantly decreased their loss of cognitive function as compared to the control aged rats. Three different markers were studied on the cellular level. The changes in these makers demonstrated that the supplement formula was able to increase proliferation of the stem cells, decrease inflammation and increase neurogenesis (growth of neurons in the brain). Overall, supplementation with the base formula showed very positive results by demonstrating an improvement in cognitive function in aged rats.

Doctors Note: If we can keep our brains healthy by protecting against oxidative stress and other foreign invaders we could possibly be able to maintain our cognitive health as we age. The results of this study demonstrate that supplementation with the nutraceutical formula in humans could be beneficial to cognitive health and prevent of neurodegenerative diseases.

5. Effects of Blue-green Algae Extracts on the Proliferation of Human Adult Stem Cells in Vitro: A preliminary study

Shytle RD, Tan J, Ehrhart J, et al. Med Sci Monit. 2010; 16(1): BR1-5.

Conclusion: When Aphanizomenon flos-aquae (AFA) algae is combined with other natural ingredients, proliferation and increased health of stem cells occur.

Summary: As a person ages their stems cells aren’t as healthy and do not regenerate as well and they also become much more susceptible to oxidative stress. Stem cells are cells that can differentiate into different specialized cells. They are found all over the body in many organs including bone marrow, peripheral blood, umbilical cord blood, spleen and more. Stem cells serve as a repair system for the body, so the death of and damage to the stem cells can result in a reduction in the body’s ability to heal itself.

The base formula is a formulation that has previously been tested for its ability to proliferate adult stem cells. The base formula is made up of blueberry extract, green tea extract, carnosine and vitamin D3. AFA research indicates that it may also have the ability to proliferate adult stem cells. Water and ethanol extracts of whole or cellular AFA was used studied in vitro, AFA’s effect on adult stem cells. Various doses of AFA (0.0625 – 0.5 mg/mL) were tested alone and in combination with the supplement base formula.

AFA, in high doses, alone had moderate results on the proliferation of adult stem cells. However, when a high dose of AFA was combined with the base formula it increased the proliferation. The ethanol extract of cellular AFA had the best results. These results suggest that the formula combined with a high dose (0.5mg/mL) of ethanol extract of AFA may increase proliferation of stem cells.

Doctors Note: Stem cells are cells that can differentiate (can develop into many different types of cells) into different specialized cells, within the organ or location they originated. This allows them to act as a repair system in various tissues in which they are located. There are two types of stem cells, embryonic and adult stem cells. Embryonic stems cells are just that, stem cells from an embryo and adult stems cells are from both children and adults.

As a person ages, these stem cells do not regenerate as well and become more susceptible to oxidation. Oxidation is when a free radical steals an electron, stabilizing itself but in turn making the other cell an unstable free radical. If a stem cell is oxidized it is damaged and can no longer do its job of repairing tissues.

Stem cells treatments are currently a hot topic in research. In stem cell treatment healthy stem cells are used and introduced to damaged tissue, diseased areas or injury. This treatment has the potential to treat cancer, Parkinson’s disease, type II diabetes, Celiac disease, cardiac failure and more.

Stem cells are very important to our health and to the future of medicine. AFA extract blended with other natural ingredients have been shown to have the ability to increase stems cell proliferation and prevent oxidation of the cells. Supplementing with the nutraceutical formula can be beneficial to those who are aging and losing the ability to regenerate and maintain the health of their stem cells.

6. Review: Nutraceutical Intervention Improves Older Adults’ Cognitive Functioning 2015

Brent J. Small, Kerri S. Rawson, Christina Martin, Sarah L. Eisel, Cyndy D. Sanberg, Cathy L. Mc Evoy. Paul R. Sanberg, R. Douglass Shytle, Jun Tan, and Paula C. Bickford

Conclusion: Older, cognitively intact adults between the ages of 65-85 who participated in a 2-month study where the supplement-based nutraceutical was consumed on a daily basis improved significantly on two measures of processing speed. The participants in the placebo group did not experience a change in performance. The results of the study suggest the potential for similar interventions in order to improve the cognitive health of older adults.

Summary: It is estimated that 87% of the population of the United States will experience normal age-related declines in cognitive function. This is in contrast to the extreme losses experienced by those with dementia-type disorders. A substantial amount of research has been conducted in recent years, searching for interventions that may help lessen, or delay, normal age-related declines in function. Potential interventions have included physical exercise, cognitive training, and cognitive stimulation. Great interest has also been given to diet, and dietary supplements.

In this study, focus was placed on the role of oral supplements—non-vitamin polyphenols–on the cognitive performance of older adults, not impaired by cognitive disease. The study was a short-term (2 months), randomized clinical trial, examining the cognitive performance of older adults after consumption of the supplement. Various cognitive tasks were performed at baseline, and then again after being randomized to either a supplement or a matched placebo. The study was double-blinded, and participants either received a placebo, or the supplement plus BioVin (see “Notes” below). It was suggested that participants take the supplement with food.

Parameters tested included episodic memory, processing speed, verbal ability, working memory, executive functioning, and complex speed. Tests were performed at baseline, and two months later.

The pill-base supplement contained a proprietary formulas of ingredients: Blueberry; green tea extract (95% polyphenols); carnosine; VitaBlue (40% polyphenolics, 12.5%anthocyanins from blueberries); Vitamin D3 (2000 IU per serving); and grape polyphenolics, including 5% resveratrol.

Several studies have reported the benefits of non-vitamin polyphenols on the cognitive health of older adults. Greater intake of blueberries and strawberries were also associated with slower rates of cognitive decline.

Participants in the study were required to meet certain criteria: They must be between 65-85 years; native English speaking; able to understand/sign the consent form; and no evidence of dementia. Exclusion criteria: history of known allergies to components of the study supplements; use of high-dose antioxidant supplements (other than those provided in the trial); depressed mood. The participants were “very high functioning” according to MMSE (Mini-Mental State Examination) scores, and also possessed high levels of educational attainment. Other comparative studies have used subjects who were already experiencing memory deficits.

Cognitive tests included: episodic memory; processing speed; verbal ability; working memory; executive functioning; and complex speed. Specific known tests were used to assess these criteria. Immediate recall, and delayed recall were assessed by these tests.

Limiting factors: The participants were all very high functioning to begin with, therefore, including participants who are already experiencing cognitive declines may lead to more vigorous results. Also, the length of the study, 2 months, may have been too short. Increasing the length of time for the study may lead to maximal results. Finally, the mechanism of action is not conclusive. Including other parameters in the study may allow researchers to identify the manner in which the supplement impacts cognitive function.

Results show that when the formula was consumed on a daily basis by older adults, they demonstrated a significant improvement in two measures of processing speed. This study suggests that the use of non-vitamin supplements may improve cognitive function in older, aging adults.

Notes: The base formula is the designation assigned to a combination of ingredients that were used to promote stem cell generation in research studies. This formula included blueberries, amino acids (carnosine), vitamin D, and green tea.

The ingredients in the supplement are rich with antioxidants, therefore they have antioxidative, as well as anti-inflammatory properties.

Carnosine is an amino acid that is concentrated in brain and muscle tissue. It has been shown to reduce the rate at which the telomeres on our chromosomes become shortened. These structures are located at the end of chromasomes, which after repeated cell division, over time, become shorter.

Carnosine is also associated with reduced glycolysis—the process, it is thought, in which aging is accelerated. Glycolysis is the breakdown of glucose. Advanced glycation is associated with several degenerative diseases, among them, Alzheimer’s disease.

BioVin is a registered product produced by Cyvex Nutrition. BioVin is a grape extract–a super-antioxidant–and is one of the highest sources of naturally occurring resveratrol.

Polyphenols are antioxidant phytochemicals that help combat free radical damage.

VitaBlue is a registered product, a line of blueberry powders/extracts that are rich in polyphenols (anthocyanins).



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