Brain Regeneration Key Nutrients Support The Growth of Brain Cell Neurites and Dendrites
There are two basic cell populations in the human body—the dividing (or mitotic) cell populations and the non-dividing (or post-mitotic) cell types. Brain cells, or neurons, for a long time were considered non-dividing post-mitotic cells that formed during embryogenesis and never replaced themselves.
We now know that brain cells can, under certain conditions, replace themselves and regrow their neural communications networks. What is especially true is that neurites and dendrites, the long filament or root-like terminal branches that are extensions of the brain cells themselves, can regrow and elongate when given the proper nutrients. Neurites and dendrites comprise the wiring communications network that allows brain cells to communicate with each other. Loss of brain cells with age is a normal process, but the loss of neurites and dendrites disrupts the neural communications network severely, preventing brain cell “cross-talk” and is a far more serious matter. Senescence of the central nervous system is characterized by a loss of neurons, neurites and dendrites and results in physiological and behavioral impairments. It is believed that reductions in the levels of growth factors, like nerve growth factor and other trophic growth factors leads to major declines in brain cell performance and degenerative diseases.1 The good news is that certain supplements act as growth factors or stimulate the brain to produce growth factors to maintain and rebuild the neural communications network.
In 1991, it was discovered that the presence of acetyl carnitine increased the effects of nerve growth factor on the outgrowth of neurites from brain cells 100 times greater than when just nerve growth factor itself was present. This was an interesting observation at the time but nerve growth factor is an internally produced protein in the brain and it was not really known how to stimulate or regulate its production.2
In 1995 it was discovered that the supplement acetyl carnitine arginate mimicked the effect of nerve growth factor and caused neurite outgrowth of PC12 cells “in a manner similar to that elicited to by nerve growth factor (itself).”3 Synergy between acetyl carnitine arginate and acetyl carnitine had earlier been demonstrated when both were tested separately and together on brain cells and found to be highly synergistic in the production of the neurotransmitters GABA, glutamate, somatostatin and other brain peptides.4
Synergistic Action on Brain Cell Regrowth
The reason the two carnitines work synergistically on brain cell regrowth came from the observation that acetyl carnitine creates nerve growth factor receptors for nerve growth factor or its mimic acetyl carnitine arginate to act on.2 So, the one carnitine grew the receptors that NGF acted on, thereby regrowing neurites, and the other compound mimicked the effects of nerve growth factor itself. The two pieces of the puzzle were finally put into place.2-3
Acetyl carnitine and acetyl carnitine arginate are two synergists that regrow brain cell neurites and dendrites so powerfully that the average length of neurites produced by the mixture of the two resulted in a 19.5 percent increase in neurite outgrowth with the mixture compared to neurite outgrowth of 5.6 percent using acetyl carnitine alone in brain cell cultures.3
In addition, acetyl carnitine arginate protects neurons against the toxicity caused by the presence of beta amyloid plaque found in old brain cells.5 Beta amyloid production is strongly implicated in the development of Alzheimer’s disease and is found in great abundance in Alzheimer’s brains. When beta amyloid was added to healthy human brain cell cultures, neurotoxicity took place in 5 days and cell death occurred within 8 days. Acetyl carnitine arginate added at the same time completely prevented or “reverted” beta amyloid toxicity by preventing its disrupting effect on the normal brain cell’s calcium balance, or homeostasis.5
Since 1988, it was known that the buildup of lipofuscin, another oxidized protein found in all older cells, was reduced in brain cells when acetyl carnitine was fed to rats as they aged.6-7 Acetyl carnitine also prevented emotional changes that occur in older rats, like increased rearing behavior and decreased locomotor activity and even in advanced age kept this behavior to the levels seen in younger rats.8
Other studies have demonstrated that acetyl carnitine prevents a variety of structural changes to the aging brain from the hippocampus, prevents decreases in receptor site sensitivity, and prevents loss of receptors in various areas over the brain. Within seven days, treatment with acetyl carnitine increases serotonin and dopamine output in rat brains. Acetyl carnitine also protects rats against the emotional effects of a chronic stress reaction called escape behavior.9
In several human trials, acetyl carnitine improved pain, nerve regeneration and sensory perceptions in patients with diabetic neuropathy.10 A meta-analysis, or a summary of all the studies to date using acetyl carnitine in mild cognitive impairment and mild Alzheimer’s disease showed significant improvements in these conditions.11 Acetyl carnitine in randomized studies was successfully used for chronic fatigue syndrome12 and fatigue in multiple sclerosis.13 It also was used successfully in depressed patients, for cognitive defects in alcoholism, and in patients with organic brain syndrome and cerebrovascular insufficiency.14-17
In many early studies, acetyl carnitine has been proposed to prevent brain aging,8, 18 and given its successful clinical history in the brain since these proposals, it is a shining star in the field of prevention of the progression of already-existing brain diseases in intervention studies. It also has proven itself in brain regeneration in animal and human brain cell studies. Together with the proven synergy between acetyl carnitine arginate and acetyl carnitine in regrowing neurites and dendrites, it is a vitally important dietary supplement for the brain.
Other Brain-Regenerating Nutrients
Uridine, or its most common salt, uridine-5-monophosphate, UMP, is a building block of RNA and DNA and, like acetyl carnitine arginate and acetyl carnitine, it is important to brain health. Uridine-5-monophosphate is the usual dietary source of uridine, found in the milk of mammals. Recent research is increasingly showing that uridine is essential for growth and development throughout life.19 It was once thought that only infants needed uridine during early developmental stages since mature mammals are capable of synthesizing their own uridine. Uridine monophosphate is still routinely added to all infant and most parenteral formulas. Uridine monophosphate has the phosphate group removed in the body by the phosphatases and when uridine is transported into the brain, the body again adds the phosphate group to cross the blood-brain barrier.20
In the 1960s, it was discovered that uridine is an essential ingredient for adult brain functioning. In 1968, one researcher found that uridine is the real dietary source of cytidine, a building block of the cell membrane component and signaling agent, phosphatidylcholine, which is necessary for memory and is a major component of cell membranes.22 Phosphatidylcholine levels decline with age in all mammals and these declining levels appear to play a major role in memory loss.
A great deal of brain research, especially when it comes to memory and cognition, is conducted with gerbils and rats because they have close similarities to human brain structure. Gerbils, in particular, lose cognition in a manner strikingly similar to humans.23
Research into the 1970s showed that rats that watched visual stimuli and then were required to perform training tasks took up more uridine into their brains than rats not required to perform tasks. It was also shown that rats that were exposed to visual stimuli had increased uptake of uridine into the visual areas of the brain and needed uridine for memory in responding to the visual stimuli. It was becoming apparent that uridine plays an important role in memory retention.24
In 2000 it was shown that human brain cells when exposed to uridine for 4 days had increased neurite outgrowth and neurofilament expression. A variety of chemicals that prevented incorporation of nucleotides into brain cells all prevented the neurite outgrowth in the brain cells caused by uridine, showing that uridine was responsible for the neural regeneration.25
In 2005, a study confirmed that uridine added to brain cell cultures stimulated neurite outgrowth branching and increased the number of new neurites per cell. The researchers found that uridine stimulated neurite outgrowth and branching by two different pathways—it enhanced phosphatidylcholine synthesis, as was previously shown in the earlier studies, but it also blocked receptors that stopped neurites from growing.26
In the same year, a study showed that orally administered uridine-5-monphosphate given to aged rats increased the release of dopamine in the right striatum of their brains to a level of 341 compared to a control group level of 221, a 35 percent increase. Biomarkers of neurite outgrowth, neurofilament-70 and neurofilament-M protein levels increased to 182 percent and 221 percent higher than in the control rats. The study demonstrated that even in old rats, oral uridine intake increases neurotransmitter release and neurite outgrowth in vivo.27
Gotu kola (Centella asiatica)
Gotu kola is a perennial plant native to India and has been used in Ayurvedic traditional medicine for thousands of years. It is mentioned in the ancient Chinese Shennong Herbal during the Tang dynasty 2,000 years ago. Gotu kola and its extracts have been incorporated into the Indian pharmacopeia in the early 1800s and officially registered as a drug in France in the 1880s.
Traditionally, Gotu kola has been used for nervous disorders such as senility and epilepsy and a brain tonic to improve memory. It has been called a “brain food” and has been recommended for overstressed people, depression, to improve reflexes and to prevent nervous breakdown. Gotu kola has also been well-known for improving circulation in patients with phlebitis and peripheral neuropathy.28
Scientific research into Gotu kola extracts and its effects on the brain really only began in earnest in the past decade. In 2002, Gotu kola water extracts were administered to rats where it improved their cognitive function in terms of learning and memory in a standard shuttle box avoidance and step through test. Brain levels of malondialdehyde (MDA), the most prominent final breakdown product of cell membrane damage was reduced and brain levels of the endogenous antioxidant glutathione were increased.29
In 2003, the same researchers again showed improved cognitive function in rats in two well-accepted tests for improved intelligence. They confirmed the reduced MDA brain levels and increased brain glutathione levels.30
A breakthrough year occurred in 2005 regarding the number of studies published using Gotu kola extracts on brain function and structural changes. In one study, where Gotu kola was given to mice during postnatal development stage “(the) extract caused brain cell dendrite outgrowth and branching of dendrites in the hippocampal area of the brain.” This showed the extract “can influence the neuronal morphology and promote the higher brain function of juvenile and young adult mice.” In other words, permanent structural out branching of the neural network of the brain was observed and this resulted in higher brain functioning.31-32
In the same year, Gotu kola alcohol extract stimulated a marked increase in neurite outgrowth in human brain cells. It was shown than many different fractions of Gotu kola extracts produced neurite branching and outgrowth from the human cells, proving that there are several active principles in Gotu kola causing this growth. These active principals were identified as asiaticosides and asiatic acid. When the alcohol extract was added to the drinking water of old rats “(they) demonstrated more functional recovery and increased axonal regeneration (of neurites and dendrites), larger calibers of axons and greater numbers of myelinated (sheath-covered) axons.” The authors concluded “taken together, our findings indicate that components in Centella ethanolic [Gotu kola] extract may be useful for accelerating repair of damaged neurons.”33
The most desirable Gotu kola extract to use is a hydro-alcoholic extract standardized to a much higher percentage of active asiaticoside principles than the vast majority of Gotu kola extracts.
Acetyl carnitine increases the effects of nerve growth factor 100 times when in NGF’s presence. It increases the expression of nerve growth factor receptor sites, which nerve growth factor acts on to regrow neurites and dendrites. Acetyl carnitine arginate mimics the effects of nerve growth factor itself. The two supplements act synergistically.
Uridine is another supplement that has been shown to regrow neurites and dendrites during growth and development stages in vivo orally. It has been shown to stimulate neurite-dendrite outgrowth in older animals, too, while improving their mental abilities.
Gotu kola improves cognition in older animals while stimulating neurite-dendrite growth and out branching in key areas of the brain because of the presence of several active principals called asiaticosides. It improves cognition and outgrowth in both older animals and also during the growth and development stages of younger animals.
Combining these four brain-regeneration nutrients can have a dramatic effect on cognitive health.
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