The Science

Introduction

The processes leading to neurodegeneration include: a) misfolding of alpha-synuclein that fails to be cleared from the brain, which in turn stimulates neuroimmune responses; b) elevations of intracellular calcium levels, affecting mitochondria and resulting in cellular energy depletion; c) iron overaccumulation causing oxidative stress, d) impacted mitochondrial function, and e) hyperinflammatory state, all of which ultimately impacts the health of neurons, which could contribute to neurodegeneration as shown in Figure 1.

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Fig. 1 Multiple processes contributing  to neurodegeneration.

All of these processes take place in the body at different times and different rates. Therefore, it is difficult to believe that a single supplement aimed to support the body in addressing just one of these processes would be enough. Therefore, we have specially curated a blend of nutritional supplements grounded in research aimed at optimizing the body's ability to protect the health of neurons and microglial cells*.

Research studies on certain ingredients reported significant positive neuroprotective outcomes in pre-clinical models. Therefore, we've specifically chosen TUDCA, creatine and COQ10 as key premium ingredients to support healthy mitochondrial function, antioxidant activity to quench free radicals and to support a healthier inflammatory response against the natural stressors within the neurons and microglia*. We tested these three ingredients together to see if there is a combined effect in a Laboratory.

Methods:

We used stem cell-derived human dopaminergic neurons and microglial cells to evaluate for an additive or synergistic effect of these combinations on several neuronal biomarkers such as neurofilament heavy chain (NFH), tubulin, MAP2 and pro-inflammatory biomarkers IL-6 and TNF-α.

Results(1):

In-vitro experimental conditions demonstrated an additive effect of ingredients found in Versamil Brain Dopamine Health.*

Neurodegenerative dopaminergic cell lines were treated with the combination of TUDCA/Creatine/CoQ10 for 14 days and showed a 24% increase in a neuronal biomarker NFH compared to the untreated cells (Fig. 2A). Another neuronal biomarker Tubulin filament area was also increased by 16% compared to the untreated cells (Fig. 2B). None of the three individual supplements alone or in other combinations showed an increase in these measures.

NFH, Tubulin and MAP2 are involved in interactions with cytoskeletal elements, communication with other cells, and regulation of protein folding and transport. Neuron loss, regardless of cause, is accompanied by corresponding decrease of these biomarkers. Therefore, their increase suggests enhancement of well-being of neurons.

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A. Neurofilament heavy chain

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B. Tubulin filament.* P<0.05; ** P<0.001

Fig. 2 Effect of experimental conditions on neurodegenerative cell line in vitro.

Interestingly, even in the healthy control cell line treated with the combination of TUDCA/Creatine/CoQ10 for 28 days a biomarker MAP2 was increased by 10% compared to the untreated cells (Fig. 3).

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Fig. 3 Effect of experimental conditions on a healthy control cell line in vitro. MAP2. * P<0.05

Effect of experimental conditions on Human Microglia (inflammatory) cell line in vitro

The combination of TUDCA/Creatine/CoQ10 reduced levels of proinflammatory biomarker IL-6 demonstrating statistical significance. Whereas,
the individual ingredients tested separately did not show statistically significant reduction (Fig. 4A).

Neither creatine, nor CoQ10 alone showed any substantial reduction in another pro-inflammatory biomarker TNF-alpha. While TUDCA alone reduced TNF-alpha, the triple combination of TUDCA/Creatine/CoQ10 showed much more significant decrease in that biomarker  suggesting synergistic combined effect (Fig. 4B) of that combination in vitro.

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A. IL-6.

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B. TNF-alpha. * P<0.05; ** P<0.001.

Fig. 4 Effect of experimental conditions on pro-inflammatory biomarkers in vitro.

  • Conclusion

    The collective findings on TUDCA, CoQ10 and Creatine highlight their additive potential in supporting neuronal health. Their diverse mechanisms of action address various aspects of brain pathology, specifically oxidative stress, mitochondrial dysfunction and hyperinflammatory state.

    We used cellular Lab experiments  to illustrate the unique advantage of combining these ingredients to achieve better results. Certainly, clinical trials confirming these findings in humans are needed.

    Versamil Brain Dopamine Health is a combination of three dietary ingredients TUDCA, CoQ10 and Creatine that was specially designed by an Expert Neurologist to help support the health of dopamine neurons and microglia.

    (1): Combination of tauroursodeoxycholic acid, co-enzyme Q10 and creatine demonstrates additive neuroprotective effects in in-vitromodels of Parkinson’s disease