/ 17. Nutritional & Herbal Approaches

updated 22.5.2009

17. Nutritional & Herbal Approaches

3) Ginkgo Biloba's Neuroprotective Effect

There are many nutritional and herbal approaches that can enhance overall physical function after SCI, including for example the following:

CREATINE: SCI STRENGTH ENHANCER: Creatine is a common nutritional supplement used by athletes to build-up muscles and strength. Several scientific studies suggest that creatine can also enhance strength in individuals with physical disability, including SCI. Furthermore, animal studies indicate that creatine exerts a neuroprotective effect after injury.

- click to enlarge -

Our bodies contain more than 100 grams of creatine, mostly in our muscles, heart, brain, and testes. Physical activity stimulates primarily the liver to produce about two grams of creatine daily from three key amino acids: glycine, arginine, and methionine. The creatine is then sent through the blood and transported into muscle cells.

Creatine can also be provided by diet, especially one rich in meat and fish. Vegetarian diets, however, often lack not only creatine, but also the methionine precursor needed for internal production. For comparison’s sake, a pound of meat contains about 40-times more creatine than a pound of milk.

Creatine-Generated Energy: Most muscle creatine is converted into the energetically powerful creatine-phosphate. The high-energy molecular bond connecting the creatine to the phosphate group is an energy source that can quickly fuel muscle activity. This fueling, however, is mediated through the creation of yet another powerhouse molecule called adenosine triphosphate (ATP).

- click to enlarge -

ATP is extremely important because it is the body’s energy currency, expended to drive most biochemical processes. Like creatine-phosphate, ATP’s terminal phosphate group is connected by a high-energy bond that when severed provides energy needed for muscle contraction.

Under more constant or endurance working conditions, the body obtains ATP by metabolizing carbohydrates and fats, a relatively slow process that cannot generate immediately needed ATP energy.

When energy bursts are required, the body uses instead creatine-phosphate. Specifically, the phosphate group on this molecule is transferred to replenish spent ATP, transforming it into its energetically powerful form. During rest periods, creatine-phosphate is then replenished by the ATP generated by the slower metabolic processes.

If intracellular creatine-phosphate levels can be increased, for example, through supplementation, it will take longer before the short-term energy source is depleted and a switchover to slower carbohydrate or fat metabolism is needed.

Strength & Muscles: Creatine supplementation is most useful for physical activities that require intense bursts of energy - e.g., a bench press, a sprint, or games requiring energy bursts. It is less useful for endurance events, except when such events are enhanced by building-up muscle strength through creatine-stimulated weightlifting.

Creatine can build muscle mass by several mechanisms. For example, because weightlifting is exactly the sort of short-term, intense physical activity fostered by creatine, more repetitions and harder workouts can be achieved, building up muscle. In addition, however, creatine increases water uptake into the muscle, a process called cell volumizing that bulks up the muscles in a fashion that may not add much real strength.

Physical Disability & SCI: Studies suggest that creatine can enhance strength compromised by physical disability:

First, Dr. P. Jacobs and colleagues at the Miami Project have shown that creatine promotes upper-extremity work capacity in quadriplegics ((Arch Phys Med Rehabil 83, 2002). In this study, 16 male quadriplegics with complete cervical C5-7 injuries were randomly assigned to receive either 20 grams/day of creatine or placebo maltodextrin (a common food ingredient) for seven days. Treatment was then discontinued for a three-week washout period, after which the treatment groups were reversed for another seven days - i.e., the initial placebo group now received creatine, and the initial creatine group now was given maltodextrin.

Work capacity was assessed before and after each dosing period using arm ergometry, a common SCI-rehabilitation exercise. Specifically, subjects faced a series of two-minute, increasing-intensity work stages with one-minute, intervening recovery periods.

After creatine supplementation, improvements were noted in various respiratory measurements, including oxygen uptake, carbon dioxide production, tidal volume (amount of air that enters the lungs), and breathing rate. For example, 14 of the 16 subjects demonstrated increased oxygen uptake, averaging 19 %. Improvements were also noted in peak power output and increased time to fatigue.

Second, Dr. K. Adams et al (Dallas, Texas) carried out a creatine-loading study in 10 subjects with SCI (Arch Phys Med Rehabil 81, 2000). The subjects had their peak-power production tested on an upper extremity exercise machine before and after creatine supplementation. Most improved their peak-power production, with quadriplegics and paraplegics averaging 21and 13% improvement, respectively.

Third, Drs. Stephen Burns, R. Kendall and colleagues (USA) examined the effects of creatine supplementation on muscle strength in eight subjects with quadriplegia. Average age was 48, seven were men, and seven had C6-level injuries. In a double-blind crossover study (a study design in which subjects unknowingly become controls and vice versa during the study), subjects were randomized to receive either creatine supplementation or a placebo Wrist and grasping strength were evaluated before and after supplementation. Unlike the preceding studies, results suggested that no additional strength accrued from creatine supplementation.

Finally, Drs. M. Tarnopolsky and J. Martin (Hamilton, Ontario) have shown that creatine can increase handgrip, knee-extension, and ankle strength in individuals with various forms of neuromuscular disease (Neurology 52, 1999).

Neuroprotection: Animal studies indicate that creatine exerts a neuroprotective effect in traumatic brain and spinal cord injury. For example, Dr. O. Hausmann et al (Zurich, Switzerland) demonstrated that four-weeks of creatine supplementation before experimental spinal cord injury reduced glial scar formation and enhanced functional recovery in rats. In another example, Dr. A. Rabchevsky and colleagues (Lexington, Kentucky) showed that creatine supplementation spared spinal cord gray matter in injured rats (gray matter contains neuronal cell bodies and dendrites and glial cells; white matter consists mainly of axons).

VITAMIN D & BONE DENSITY: As summarized in two key articles, research carried out by Dr. William Bauman and colleagues, Bronx VA Medical Center indicates that individuals with SCI are often vitamin-D deficient (Metabolism 44(12), 1995; & J Spinal Cord Med 28, 2005).

Like astronauts who lose bone density from the lack of weight-bearing activities, paralysis causes osteoporosis. As much as 50% of lower-extremity bone mass is lost during the first several years after injury, people with complete injuries losing the most. Hence, a deficiency in bone-enhancing vitamin D further aggravates an already serious SCI problem, in turn increasing fracture risk.

Bauman believes SCI predisposes one to vitamin-D deficiency for several reasons. For example, he speculates that due to limited mobility, someone with SCI may not get as much vitamin-D-producing sunlight as the general population. Supporting this idea, other scientists have demonstrated that pressure-sore-afflicted patients with SCI, who have access to the least sunlight, have the greatest vitamin-D deficiency.

Bauman also suggests that a lack maybe be caused when health-care professionals recommend reduced consumption of vitamin-D-fortified dairy products under the mistaken belief that the calcium in such foods will aggravate kidney problems. And, he believes that many SCI-associated medicines reduce the body’s vitamin-D stores.

In his 1995 study, Bauman compared vitamin-D levels in control subjects and in 100 veterans with SCI who averaged 20 years post-injury. Subjects with SCI were twice as likely to have vitamin-D levels less than that considered normal.

- click to enlarge -

In his 2005 study, Bauman examined the effectiveness of several dosing regimens in elevating vitamin-D levels in people with chronic SCI. In one regimen, 40 subjects consumed 800 IU of vitamin-D per day for 12 months. Their mean age was 43; injury duration averaged 12 years; and 17 and 23 had quadriplegia and paraplegia, respectively. Before supplementation, 33 had below-normal vitamin-D levels; in contrast, after 12 months of supplementation, only 9 remained deficient.

Although average serum vitamin-D levels doubled in subjects, Bauman believes that even greater supplementation is needed to obtain nutrient serum levels needed for promoting optimal bone health in SCI.

GINKGO BILOBA’S NEUROPROTECTIVE EFFECTS:

Obtained from the leaves of a large deciduous tree originally from China, Ginkgo biloba is one of mankind’s most ancient medicines. Fossil records indicate the species has been around for over 200-million years, and some ginkgos at Chinese temples are more than 1,500-years old. Given the trees are highly disease and insect resistant and grow in urban environments where other trees can not, it is not surprising that they possess substances with medicinal properties.

In Europe, ginkgo is the most widely sold and prescribed plant-based medicine; in the U.S., it is one of the top ten best-selling herbal remedies. Supported by varying degrees of animal research and clinical studies, ginkgo may provide benefits for a variety of disorders, including:

	Cerebral vascular insufficiency and impaired mental performance (e.g., senility);
	Alzheimer’s disease (AD);
	Cochlear deafness;
	Senile macular degeneration;
	Peripheral arterial insufficiency;
	Erectile dysfunction;
	Depression and anxiety;
	Multiple sclerosis (MS);
	Traumatic brain injury;
	SCI.

Ginkgo operates through several potential physiological mechanisms especially relevant for neuronal health. For example, it is an antioxidant, maintains cell-membrane integrity, enhances oxygen use and metabolism, augments neurotransmission, and inhibits a form of programmed cell death called apoptosis.

Using a rat model of acute injury, Turkish investigators showed that ginkgo extract inhibits post-injury lipid peroxidation, a biochemical process that mediates secondary damage to the injured cord (Koc et al. Res Exp Med 195, 1995). Ginkgo’s inhibition was even greater than methylprednisolone (MP), a glucocorticoid-steroid drug which is now routinely administered after injury to minimize neurological damage.

More recently, Chinese investigators demonstrated that ginkgo extract is neuroprotective in rats with experimental SCI (Ao et al. Spinal Cord, 44, 2006). Specifically, after cutting the spinal cord in half at the thoracic T-9 level, rats were given either ginkgo or saline. The ginkgo-treated rats had smaller injury-related cavities, less conduction-inhibiting demyelination, and less apoptotic neuronal cell death.

FASTING: Recent paradigm-expanding research carried out by Drs. Ward Plunet and Wolfram Tetzlaff and colleagues at the University of British Columbia (Canada) suggests that fasting enhances nervous-system regeneration after SCI. Specifically, rats with experimental cervical injuries were randomized into two groups. The control animals had free access to food and water, while the experimental animals received food only every other day starting immediately after injury.

Compared to controls, fasted rats had improved gait and forelimb function. Fasting also preserved neuronal integrity, reduced the size of the injury-site lesion by more than 50%, and increased sprouting of axons. Finally, the blood level of a neuroprotective agent (called beta-hydroxybutyrate) increased 2-3 times on the fasting days. A similar neuroprotective effect has also been observed by other scientists for traumatic brain injury.

The investigators concluded that because every-other-day-fasting “is a safe, non-invasive, and low-cost treatment, it can readily be translated into the clinical setting of spinal cord injury and possibly other insults.”

Buyang Huanwu Decoction (BYHWD):

BYHWD is a Chinese herbal medicine that has been used for centuries to treat a variety of disorders, including paralysis. From a Traditional Chinese Medicine viewpoint, it’s used to “invigorate the body, promote blood circulation, and activate meridians (energetic channels).” The decoction is composed of extracts of a number of Chinese herbs or remedies, including astragalus, dong quai, red peony root, Rhizoma Chuanxiong (Lingusticum), earthworm, peach seed, and safflower.

Demonstrating that ancient wisdom often has much contemporary validity, studies indicate that BYHWD, indeed, exerts some neuroprotective and regenerative effects. For example, animal research suggests that this herbal decoction can promote nerve regeneration after stroke and both peripheral-nerve and spinal-cord injuries.

In the case of SCI, Dr. An Chen et al (China) have evaluated BYHWD in a rat model of injury in which one side of the cord was transected at the cervical level. After transection, the rats were administered either the BYHWD or a distilled-water control for eight weeks via gastrogavage (i.e., through a stomach tube). After this time period, the number of surviving neurons on the cord’s injured side for both BYHWD- and water-treated groups were compared to the neuron level on the non-injured side (i.e., a baseline comparison). Compared to the uninjured side, 78% of the neurons remained with the BYHWD-treated rats compared to only 58% of the water-treated rats. In other words, the BYHWD decoction reduced injury-related neuronal loss from 42 to 22%.

In addition, cell bodies of surviving neurons atrophied by 64% in the water-treated controls compared with 35% in the BYHWD-treated rats. In other words, BYHWD enhanced the apparent robustness of the surviving neurons.

Especially significantly, only in the BYHWD-treated rats did axons regenerate through the injury site. And, as would be expected with such regeneration, these rats recovered more forelimb function, the physical area affected by the experimental transection injury.

In another study, Dr. Lihong Fan and colleagues (China) evaluated the effects of BYHWD in a rabbit model of SCI. In this model, injury was generated by temporarily shutting off blood flow to the spinal cord’s lumbar region (i.e., ischemia), affecting hind-limb function. The rabbits were treated with either BYHWD or saline starting seven days before injury and continuing two days after injury. Hind-limb function was then measured using a scale ranging from 0 (complete paralysis) to 5 (normal function). Forty-eight hours after injury, the BYHWD-treated rabbits averaged 3.4 on this scale compared to 2.6 for the saline-treated controls.

With respect to peripheral nerve injuries, Dr. Yueh-Sheng Chen et al (Taiwan) demonstrated that BYHWD stimulates growth in regenerating nerves. In this study, a 10-millimeter gap was created in the rat sciatic nerve (a nerve that runs down the leg from the back) and then bridged by a silicon-rubber tube. Regeneration across the gap was compared in BYHWD-treated rats and control animals who received no BYHWD. Nerves regenerated across the gap in 89% percent of the BYHWD-treated rats compared to only 70% of controls.

Although these BYHWD-related improvements may appear modest, it is important to underscore that studies have shown that substantial physical function can be retained even if only a relatively small percentage of neurons survive the injury.

BYHWD may mediate its neuroprotective effects through several physiological mechanisms. For example, scientists have shown that BYHWD 1) stimulates the outgrowth and differentiation of neurites on neuronal stem cells (neurites are processes budding out from immature neurons, such as developing dendrites and axons); 2) inhibits apoptosis – a post-injury, programmed cell death of spinal-cord cells; and 3) decreases free radical generation and associated lipid peroxidation, biochemical processes that mediates secondary damage to the injured cord.

MELATONIN:

Readily available from vitamin stores and other sources, melatonin is a key hormone produced by the pineal gland. Its production is closely correlated to our sleep-wake cycle and is specifically inhibited by light and stimulated by darkness. The pineal gland converts the amino acid tryptophan into serotonin (a neurotransmitter) and, in turn, melatonin. The melatonin then is released into the bloodstream and cerebrospinal fluid, where it can interact with cells throughout the body.

Through complicated neuroanatomical wiring, photosensitive cells in the retina detect light and send signals to structures that regulate our 24-hour circadian rhythms. These signals then go out of the head to the cervical spinal cord, where are they are routed back to the pineal gland. Hence, cervical, but not lower-level, injuries will compromise the pineal gland and its melatonin production.

Called the sleep hormone, melatonin is used as a sleep-aid for insomniacs, shift workers, and jet-lagged travelers. Because it has been extensively consumed, it is presumably reasonably safe. This is important because animal studies suggest that melatonin is neuroprotective after acute injury. Although we need to be cautious in extrapolating the results of animal studies to humans, its extensive use makes it a better therapeutic candidate for acute injury in humans.

In addition to its hormonal action, melatonin is a powerful antioxidant that protects cells from damaging oxidation. Specifically, it is a highly efficient scavenger of free radicals, which, because they possess an unpaired electron, seek out another electron to achieve a more stable energetic state. Melatonin’s lipophilic structure (i.e., affinity for fat or lipid) allows it to diffuse through the membranes surrounding cells and scavenge free radicals inside the cell.

After the initial mechanical injury in SCI, a complicated physiological chain reaction generates free-radicals, which steal electrons from the lipids in cell membranes. Called lipid peroxidation, this process impairs neuronal and axonal membranes, resulting in further cell death.

Like the frequently administered methylprednisolone, animal studies indicate that melatonin inhibits lipid peroxidation and various injury-aggravating inflammatory processes. Sample studies include:

Dr. Toru Fujimoto and colleagues (Japan) examined melatonin’s neuroprotective effects in rats with experimental SCI. The spinal cords were injured at the T12 level by the pressure of a weight placed on the exposed cord. Melatonin was injected into the body cavity (i.e., intraperitoneally) at 5 minutes, and 1, 2, 3, and 4 hours after injury. Saline was injected into control rats. Because the amount of injected melatonin was much higher than endogenously (i.e., produced from within) generated levels, background levels were not considered experimentally relevant (albeit, see Ates, et al below). Compared to controls, the melatonin-treated rats had less lipid peroxidation, smaller injury-site cavities, and retained more hind-limb function.

Dr. S. F. Erten et al (Turkey) assessed melatonin’s effects in rabbits with spinal-cord ischemia produced by clamping down on blood vessels leading to the cord. Melatonin was intraperitoneally introduced either 10 minutes before or after clamping. The melatonin-treated rabbits had less lipid peroxidation.

Dr. Jin-bo Liu and associates (China) examined melatonin’s neuroprotective effects in rats with injuries produced by dropping a weight on the exposed spinal cord and dosing them intraperitoneally with melatonin. The investigators concluded that “melatonin can prevent oxidative damage, reduce neurological deficit, and facilitate the recovery from spinal cord injury.”

Drs. Tiziana Genovese and colleagues (Italy) provided further evidence of melatonin’s neuroprotective effects. In their experiments, injury was produced in rats by clipping the exposed spinal cord. Melatonin was administered once before clipping and several times afterwards. The investigators concluded “that melatonin can exert potent anti-inflammatory effects” and enhanced hind-limb functional recovery.

Dr. Suleyman Cayli et al (Turkey) compared the effectiveness of 1) melatonin, 2) the commonly used methylprednisolone, and 3) a combination of the two drugs. After injury was produced in rats by dropping a weight on the exposed cord, the drugs were injected intraperitoneally, and various assessments carried out over time. Compared to controls, improvements were noted in all three treatment groups, including enhanced neuronal conduction, recovery of motor function, decreased injury-promoting lipid peroxidation, and improved injury-site structural integrity. The combination treatment of melatonin and methylprednisolone was best at inhibiting lipid peroxidation.

Earlier, it was implied that the endogenous levels of melatonin produced by the body did not play a significant neuroprotective role after SCI. However, research by Dr. O. Ates and colleagues (Turkey) suggest that physiological background levels may, indeed, be quite important. In addition to looking at the neuroprotective properties of externally administered melatonin, the investigators assessed the effect of removing the rat’s pineal gland and, hence, the body’s melatonin source before injury. Such pinealectomy increased the amount of lipid peroxidation after injury. The investigators concluded: “These findings suggest that reduction in endogenous melatonin after [pinealectomy] makes the rats more vulnerable to trauma…”

These findings actually have considerable relevance to humans. Specifically, for a variety of reasons, including environmental, pineal functioning tends to diminish over time. In adults, melatonin-compromising calcification of the pineal gland is not uncommon, a process in which gritty deposits called brain sand accumulate in the gland. It suggests that individuals with such calcification will have more neurological damage after injury.