Thursday, June 13, 2013
Monday, May 9, 2011
Wednesday, April 20, 2011
Department of Dermatology, University Hospital Schleswig-Holstein, University of Lübeck, Ratzeburger Allee 160, D-23538 Lübeck, Germany.
CONTEXT: Both insufficient and excess levels of thyroid hormones (T3 and T4) can result in altered hair/skin structure and function (e.g. effluvium). However, it is still unclear whether T3 and T4 exert any direct effects on human hair follicles (HFs), and if so, how exactly human HFs respond to T3/T4 stimulation.
OBJECTIVE: Our objective was to asses the impact of T3/T4 on human HF in vitro.
METHODS: Human anagen HFs were isolated from skin obtained from females undergoing facelift surgery. HFs from euthyroid females between 40 and 69 yr (average, 56 yr) were cultured and treated with T3/T4.
RESULTS: Studying microdissected, organ-cultured normal human scalp HFs, we show here that T4 up-regulates the proliferation of hair matrix keratinocytes, whereas their apoptosis is down-regulated by T3 and T4. T4 also prolongs the duration of the hair growth phase (anagen) in vitro, possibly due to the down-regulation of TGF-beta2, the key anagen-inhibitory growth factor. Because we show here that human HFs transcribe deiodinase genes (D2 and D3), they may be capable of converting T4 to T3. Intrafollicular immunoreactivity for the recognized thyroid hormone-responsive keratins cytokeratin (CK) 6 and CK14 is significantly modulated by T3 and T4 (CK6 is enhanced, CK14 down-regulated). Both T3 and T4 also significantly stimulate intrafollicular melanin synthesis.
CONCLUSIONS: Thus, we present the first evidence that human HFs are direct targets of thyroid hormones and demonstrate that T3 and/or T4 modulate multiple hair biology parameters, ranging from HF cycling to pigmentation.
FULL ARTICLE IN PDF
Pharmacological Evaluation Laboratory, Taisho Pharmaceutical Co., Ltd., 403, Yoshino-cho 1-chome, Saitama-shi, Saitama 330-8530, Japan.
The length and size of hair are depend on the anagen term in its hair cycle. It has been reported that the some cell growth factors, such as VEGF, FGF-5S, IGF-1 and KGF, induce the proliferation of cells in the matrix, dermal papilla and dermal papillary vascular system and increase the amount of extra cellular matrix in dermal papilla and then maintain follicles in the anagen phase. On the other hand, negative factors, like FGF-5, thrombospondin, or still unknown ones, terminate the anagen phase. If the negative factors become dominant against cell proliferation factors according to fulfilling some time set by the biological clock for hair follicles, TGF beta induced in the matrix tissues evokes apoptosis of matrix cells and shifts the follicles from anagen to catagen. Androgenetic alopecia is caused by miniaturizing of hair follicles located in the frontal or crown part of scalp and are hereditarily more sensitive to androgen. In their hair cycles, the androgen shortens the anagen phase of follicles and shifts them to the catagen phase earlier than usual. The mode of action of hair growth effect of minoxidil is not completely elucidated, but the most plausible explanation proposed here is that minoxidil works as a sulfonylurea receptor (SUR) activator and prolongs the anagen phase of hair follicles in the following manner: minoxidil (1) induces cell growth factors such as VEGF, HGF, IGF-1 and potentiates HGF and IGF-1 actions by the activation of uncoupled SUR on the plasma membrane of dermal papilla cells, (2) inhibits of TGF beta induced apoptosis of hair matrix cells by opening the Kir 6.0 channel pore coupled with SUR on the mitochondrial inner membrane, and (3) dilates hair follicle arteries and increases blood flow in dermal papilla by opening the Kir 6.0 channel pore coupled with SUR on the plasma membrane of vascular smooth muscle cells.
PMID: 11915519 [PubMed - indexed for MEDLINE]
L-carnitine-L-tartrate promotes human hair growth in vitro
The trimethylated amino acid l-carnitine plays a key role in the intramitochondrial transport of fatty acids for beta-oxidation and thus serves important functions in energy metabolism. Here, we have tested the hypothesis that l-carnitine, a frequently employed dietary supplement, may also stimulate hair growth by increasing energy supply to the massively proliferating and energy-consuming anagen hair matrix. Hair follicles (HFs) in the anagen VI stage of the hair cycle were cultured in the presence of 0.5-50 microm of l-carnitine-l-tartrate (CT) for 9 days. At day 9, HFs treated with 5 microm or 0.5 microm of CT showed a moderate, but significant stimulation of hair shaft elongation compared with vehicle-treated controls (P < 0.05). Also, CT prolonged the duration of anagen VI, down regulated apoptosis (as measured by TUNEL assay) and up regulated proliferation (as measured by Ki67 immunohistology) of hair matrix keratinocytes (P < 0.5). By immunohistology, intrafollicular immunoreactivity for TGFbeta2, a key catagen-promoting growth factor, in the dermal papilla and TGF-beta II receptor protein in the outer root sheath and dermal papilla was down regulated. As shown by caspase activity assay, caspase 3 and 7, which are known to initiate apoptosis, are down regulated at day 2 and day 4 after treatment of HFs with CT compared with vehicle-treated control indicating that CT has an immediate protective effect on HFs to undergo programmed cell death. Our findings suggest that l-carnitine stimulates human scalp hair growth by up regulation of proliferation and down regulation of apoptosis in follicular keratinocytes in vitro. They further encourage one to explore topical and nutraceutical administration of l-carnitine as a well-tolerated, relatively safe adjuvant treatment in the management of androgenetic alopecia and other forms of hair loss.
PMID: 17927577 [PubMed - indexed for MEDLINE]
Tuesday, April 19, 2011
PMID: 18078443 [PubMed - indexed for MEDLINE]
Monday, April 18, 2011
Actovegin� is a Deproteinized Hemoderivative of Calf Blood that is obtained by ultra-filtration. The Deproteinized Hemoderivative of Calf Blood contains only physiological components, anorganic substances socle as electrolytes and essential trace elements and 30% of organic components as amino acids, oligopeptides, nucleosides, intermediary products of the carbohydrate and of the fat metabolism, and components of the cellular membranes as glycosphingolipids. One of the physiologic components of Actovegin is inositol phospho-oligosaccharides ( IPOs ). These compounds are thought to possess central and peripheral insulin effects, suggesting that a therapeutic benefit could be obtained in disorders of impaired glucose utilization. The molecular weight of the organic components is below 6000 Dalton.
The active components in Actovegin promote glucose uptake by cerebral and skeletal muscle and other cells and stimulate intrinsic glucose transport by regulating glucose carrier GluT1; Actovegin activates piruvate-dehydrogenase (PDH) and thereby leads to increased utilization of glucose by cells and formation of energy-rich substances ("insulin-like effect). (Oberermaier-Kusser et al. 1989 Actovegin also increases uptake and utilization of oxygen by hypoxic tissues and cells (which can be proven by Warburg's test) via promoting mitochondrial respiratory function and decreases formation of lactate, as a result, it protects hypoxic tissue. (Machicao, 1993; Kununaka et al. 1991)
Acute toxicity: Acute toxicity tests in mice (NMRI mice, male and female mixed) showed that the fifty percent lethal doses (LD50, calculated as dry weight) were as follows:
-intravenous administration: 2.31 g/kg;
-intraperitoneal administration: 2.97 g/kg;
-sucutaneous administration: 5.57 g/kg;
-oral administration: 7.93 g/kg
Subchronic toxicity: Experiments performed in rabbits (Deutsche Riesenschecken rabbits, female) demonstrated that there was no evidence of either macroscopic or microscopic organic pathological changes as compared to normal control animals after infusing 20% Actovegin intravenously once a day at a dose of 7.0 ml/kg, 7 days a week, for 3 months. Actovegin has no toxicity on fertility, embryo and fetus; it has no teratogenic, mutagenic, or carcinogenic effects.
Actovegin� is a calf-blood derived hemodialysate. Since it is not a single-component drug, conducting a pharmacokinetic study is impossible. However, for its bioavailability, certain pharmacological studies in animals may provide some reference: glucose tolerance studies in rats showed that blood glucose level started to decline as early as at 5 minutes after intravenous administration of Actovegin , and the effect reached its peak at 180 minutes after administration. (Bachmann et al. 1968) improved at 15 minutes after parenteral administration of Actovegin . (Quadbeck et al. 1964)
Disturbances in the cerebral circulation and nutrition (ischemic insultus, cranio-cerebral traumas).
Disturbances of peripheral (arterial, venous) blood flow and sequels resulting from these disturbances (arterial angiopathy, ulcus cruris).
Burns, scalds, erosions.
Wound-healing impairment: torpid wounds, decubitus;
Radiation-induced skin and mucous membrane lesions (prophylaxis and therapy).
Mode of action
Actovegin produces an organ-unrelated increase of the cellular energy metabolism. The activity is confirmed by measurement of the increased uptake and of the elevated utilization of glucose and oxygen. These two effects are coupled and they result in a rise of the ATP-turnover and thus in a greater provision of energy in the cell. In deficiency states with impairment of the normal functions of the energy metabolism (hypoxia, substrate deficiency) and in states of increased energy requirement (reparation, regeneration) Actovegin promotes the energy-dependent processes of the functional metabolism and of the conservation metabolism. An increase of the blood supply is seen as a secondary effect
Effects related to therapeutic indication:
Effects related to glucose transport
-The IPO fraction of Actovegin demonstrated a positive effect on glucose carrier activity( GLUT1) in the plasma membrane
-Actovegin stimulated glucose uptake in cerebral tissues, as well as other isolated animal tissues
Effects related to glucose utillization
-The IPO fraction of Actovegin activated glucose oxidation as well as the PHD complex
-The IPO fraction of Actovegin acts indirectly on the citric acid cycle by causing increased formation of acetyl COA
Effects related to oxygen uptake on energy metabolism
-Actovegin increased the respiratory capacity of mitochondria
-Actovegin improved oxygen uptake in Anesthetized dogs
-Actovegin demonstrated a positive effect on cerebral metabolism of rats under conditions of Hypoxia
Safety of Actovegin
The manufacturer Nycomed Austria GmbH confirms that all measures are in place to guarantee the TSE safety of Actovegin. According to the actual guideline EMEA/410/01 final (issued in February 2001, replacing CPMP/BWP/1230 REV.1) and the Final Opinion of the Scientific Steering Committee on the geographical BSE risk (issued in July 200) the safety of a medicinal product is determined by several important factors:
1. Animals as source of material: the most satisfactory source of materials is from countries which are free of BSE and have appropriate surveillance systems. Materials may be used from countries with a low BSE incidence. The calf blood used as raw material for Actovegin derives from calves born, raised and slaughtered in Australia. Australia is officially categorised as BSE � and Scrapie free country by the OIE (World Organization for Animal Health) and the SSC (Scientific Steering Committee of the European Union). Surveillance systems are in place.
2. Parts of animal bodies and body fluids used as starting materials: tissues and body fluids are categorised in four categories (from category I = high infectivity like brain to category IV= safest category, no detectable infectivity like blood and milk). Actovegin is manufactured from calf blood, blood is in the safest tissue category IV.
3. Age of animals: the sourcing from young animals is seen as very important safety factor. The blood used as raw material for Actovegin production derives from calves below six months of age. The calves were never fed animal carcasses fodder and are declared fit for human consumption, as all proven by veterinary certificates. Moreover the traceability of every Actovegin batch back to the individual calves as blood donors is ensured. The mother cows (dams) of the calves are also known.
4. A production process should be designed which is thought to remove or inactivate TSE agents. Validation studies are currently not generally required. The manufacturing process of Actovegin is BSE validated, thus proven to be capable of removing hypothetically present TSE agents.
5. A risk analysis was performed according to the PhPMA system showing that Actovegin is absolutely BSE safe. Moreover Actovegin is a natural drug with proven efficacy and also a general favourable safety profile over decades. These benefits cannot be substituted by a chemical drug. In conclusion, Actovegin is BSE safe and fullfills even more safety measures than required by actual guidelines
Actovegin-Ergogenic Aid or Not results in beneficial effects in several pathophysiological clinical settings including malfunction of the blood circulation and trophic disturbances in the brain, impairment of peripheral blood circulation and associated diseases, dermal transplants and acute and chronic wounds. Here, we give an overview of the pharmacodynamic actions of calf-blood hemidialysate and its beneficial effects in a variety of clinical settings.
By Chad Robertson B.Sc (KIN), B.Sc (PHARM)
There has been a great deal of hype in the media of late regarding the drug Actovegin after reports that a world renown physician who treated Tiger Woods is under investigation for apparently using it. My intentions of this article is to educate the public on the pharmacological properties of Actovegin and how to derive the same clinical applications using natural nutrients. As reported, Actovegin is a protein free blood derived extract from calf used for treating dementia, cerebrovascular insufficiency, and periperal vascular resistance. It is manufactured by a European based pharmaceutical company, Nycomed Austria
Properties of Actovegin
An extensive Medline literature search revealed older German and Russian studies focusing on Actovegin's physiologic effects on glucose metabolism and cerebral circulation. There are no reports on its use in improving athletic performance and scant reviews for it's treatment of sports related injuries. Nevertheless, since its introduction, the athletic community has realized the potential of Actovegin to increase mitochondrial ATP energy production through increased glucose and oxygen utilization.
Improvement of glucose metabolism
Jacob S et. al. (1996) was one of the first to show that Actovegin stimulated the uptake of glucose into adipocytes by inositol-phosphate-oligosaccharides (IPO), a key component of Actovegin. IPO is thought to possess insulin-mimicking effects by regulating glucose carrier activity 1, 2. Improvements in glucose tolerance occurs without affecting endogenous serum insulin levels and this effect was seen in diabetics rather than those with normal carbohydrate metabolism 3.
Increase peripheral blood flow
Restrictions in peripheral blood flow due to arterial occlusive disease results in muscle pain during rest and exercise. A study was undertaken to determine the effects of intravenous (IV), intraarterial (IA) Actovegin administration and physical exercise on peripheral arterial occlusive disease 4.
Over a four week period, patients who received IA injections achieved a pain free walking distance of 44.9% compared to 37.8% in the IV group. However, physical exercise showed improvements in pain free walking distance of 66.9% although the results were not considered significant compared to IA Actovegin.
Hypoxic states and dementia
The parietal cortex is responsible for processing visual information and spatial directed attention and shrinkage to the area leads to dementia. It appears Actovegin improves the cognitive processing in the parietal cortex in age associated memory impairment 5. Kanowski S et. al. 1995 showed improvements in organic brain syndrome patients in social behavior and mental performance with injections of Actovegin compared to placebo 6.
Actovegin improves energy metabolism in hypoxia by increasing uptake of glucose and oxygen 7.
Rapid recovery times from sports related injuries are important for athletes. Local injections of Actovegin has been shown to significantly shorten recovery time in muscle injury compared to placebo 8.
How does Actovegin compare to ACS
Autologous Conditioned Serum (ACS) is produced by physical and chemical stimulation of whole blood to increase the concentration of specific growth factors such as FGF-2, TGF-beta1 and HGF. During muscle regeneration, a host of growth factor are involved in the repair process but FGF-2, TGF-beta 1, and HGF are key regulators of muscle satellite cell activation. Wright-Carpenter et.al. 2004 compared the effects of ACS against Actovegin/Traumeel (control) for muscle strains. Local injections of ACS shortened recovery time to healing (as shown on MRI scans) and showed an almost complete regression of edema and bleeding after 14 days compared to the control group which only possessed mild effects 9.
Comparison to alternative products
It is interesting to note how Actovegin's biochemical and physiological properties compares to other products currently used in similiar disease states.
Actovegin has been proposed to increase glucose utilization by regulating glucose transporter protein (GLUT-1). Lipoic acid mimics insulin action by affecting GLUT-1 and GLUT-4 10. Glut-1 involves glucose transport into red blood cells and the brain whereas Glut-4 transports glucose into fat and muscle cells and has a greater impact on blood sugar levels than Glut-1.
Skeletal muscle depends on insulin to transport glucose into myocytes where it is used to produce energy. During exercise, muscle contractions upregulate expression of GLUT-4 thereby reducing blood sugar levels and overcoming insulin resistant skeletal muscle 11. Another important property of Lipoic acid is it's ability to strengthen antioxidant defenses by increasing glutathione and protect against exercise induced oxidative stress 12.
The hypoglycemic properties of taurine appear to be much greater after glucose supplementation rather than administration before a glucose challenge 13. Taurine acts by stimulating the secretion of insulin from pancreatic beta cells in addition to protecting it from lipid peroxidation through it's antioxidant action. Taurine's antioxidant property also extends to skeletal muscles where it may enhance exercise performance by attenuating damage to muscle tissues induced by exercise 14.
Vinpocetine, a derivative from the periwinkle plant, has been used as a nootropic to enhance mental function and as a drug to treat cerebral ischemia. Like Actovegin, vinpocetine can increase cerebral blood flow in ischemic stroke patients especially in areas which concentrated the drug the most 15. However, it's effect on the metabolic rate of glucose in the brain is minimal and the clinical use of vinpocetine in dementia is not conclusive 16.
Similiarities exists between Actovegin and the natural products lipoic acid, taurine and vinpocetine to improve blood flow and increase glucose disposal. Current well designed studies on it's use in sport injuries and enhancement of performance has yet to be conducted.
Thursday, April 14, 2011
Wednesday, April 13, 2011
Well, truth be told, statins to the big pharmaceutical companies, are like the major blockbuster movies that Hollywood create - filled with hype and special effects to wow the audience. And just like these blockbuster movies, there are major flops too. Statins are definitely one of those, that flop big time.
But the difference between a bad movie and a bad drug is that you still live after watching a bad movie. You however, slowly die if you get prescribed a bad drug. Because what the doctor doesn't know about nutritional medicine may be killing you.
Let me share with you why this is so.
What is Coenzyme Q10 (CoQ10)?
First, you need to know what coenzyme Q10 (CoQ10) is. CoQ10 is needed for the functioning of mitochondria, which is the microscopic power stations found in every cell. They generate ATP, which is the form of energy all forms of life need. Cells with the highest energy demands, contain the highest levels of CoQ10, and CoQ10 is needed for good muscle function. The most important dietary sources of CoQ10 are meats and fish.
The Danger of Synthetic Statins
Now, both CoQ10 and cholesterol are synthesized from the same substance, mevalonate. And statin drugs such as Lipitor, Zocor, etc, inhibit the body's synthesis of CoQ10 because statin drugs are supposed to inhibit cholesterol. Please note that this is not a "side effect," of statins, but a direct, inherent function of the drugs. In fact, the use of statins can decrease the body's synthesis of CoQ10 by as much as 40%!
The depletion of CoQ10 can lead to muscle pain and damage. And-Muscle tissue damaged by a statin drug is certainly contrary to maintaining good health, especially when the damaged muscle tissue is part of the heart muscle-the very organ you are taking the drug to protect!
So, can you imagine that the drug, your doctor prescribed to save you, was actually preventing your body from recovering? Of course, many doctors deny the occurrence of any side effects, and tend to dismiss them. This is mainly due to the fact that pharmaceutical manufacturers producing statin drugs rarely publicize their side effects, and when they do, they are buried in the small print or minimized to a very small percentage of total users.
After all, if you had spent billions of dollars in the researching and developing a drug, you would need to recover the cost, wouldn't you?
Are There Natural Statins?
Of course there are natural Statins such as Red Yeast Rice, Garlic and Hawthorn and Policasanol. Red Yeast Rice contains a naturally occurring statin called Mevastatin. And as with most herbal products, it contains many other natural substances, some of which act synergistically to reduce negative effects. On the other hand, synthetic statin drugs contain only one isolated synthetic chemical. However the problem with natural statins is that they are seldom produced in accordance to pharmaceutical standards, or strict quality control.
Something even better than Natural Statins: Great Synergy between CoQ10 and Alpha Lipoic Acid
It is important to note that if you take any item containing a statin, even a natural one like that in Red Yeast Rice, you should supplement with at least 120 mg of CoQ10 daily to replace that which the statin depletes. Some quality CoQ10 supplements however need a lesser amount than 120mg because they are paired with Alpha lipoic acid (DHLA). Alpha lipoic acid is involved in mitochondrial energy metabolism and recycling oxidised CoQ10. In other words, the alpha lipoic acid would allow the CoQ10 to be absorbed deeper into the blood plasma, and most of the CoQ10 can be directed to the cells that need it most. Hence, even if you find that you have a bottle of CoQ10 supplements that contains more than 100mg of CoQ10, and no alpha lipoic acid with it, chances are, much of these CoQ10 would not be absorbed well into the cells.
So while waiting for the CoQ10 issue to be settled in future statin studies, which will probably never see the light of the day, you may wish to maintain your cholesterol level by keeping a better diet and to supplement yourself with quality vitamins and minerals before your cholesterol levels start rising. Take natural statins as the second resort. In most cases ensure that your bottle of CoQ10 has alpha lipoic in it so that your healthy cholesterol goals would be met, and you would never ever need to take synthetic statin drugs.
Arginine alpha ketoglutarate or AAKG is a chemical compound made from combining the salt of arginine and alpha ketoglutaric acid, two important chemical compounds necessary to produce the compound nitric oxide. It is a well known compound because it is widely sold in the market as a dietary supplement that builds muscle mass.
Arginine alpha ketoglutarate supplement is sold in the market for body building purposes. It is administered to patients who have just undergone surgery to promote hormone production and release of insulin for the purpose of healing wounds in a speedy manner. AAKG has the ability to speed up recovery after a serious injury and is also used to treat severe burns and other traumatic damage to the body.
Previous laboratory experiments show that AAKG supplementation dramatically increased collagen production deposited in a wound as evidenced by the presence of the substance hydroxyproline in the wound.
Wound healing is greatly enhanced by the arginine content in AAKG and increases the producttion of hydroxyproline levels in the wound area when tested among the diabetic laboratory animals. AAKG supplementation also significantly increased the amount of fluid nitrate and nitrite levels in the site of the injury.
It is also believed that this substance can reduce blood pressure. Nitric oxide, which is produced from arginine has the ability to dilate blood vessels resulting to the relaxation of muscles in the arteries, arterioles and veins. It is believed that the nitric oxide content in AAKG is responsible for the production of muscle proteins in the body and further enhances muscular strength and endurance, however further research is needed to confirm this claim. It ensures a regular supply of healthy blood to the muscles and other parts of the body.
During great stress and traumatic injury, the glutamine and arginine content found in our skeletal muscles are significantly increased with arginine alpha ketoglutarate supplementation.
It is also believed to increase the amount of growth hormones especially in children where a study showed that the AAKG supplementation indeed increased the levels of growth hormones and amino acids in the body.
The benefits from arginine alpha ketoglutarate are almost the same as those derived from arginine. It is used to speed up the healing of wounds especially after surgery and repair of cells and tissues of the body after severe wounds and body injury. It also treats headaches caused by severe migraine and treats impotence among the male population.
Monday, April 11, 2011
L-Arginine as a Potential Ergogenic Aid in Healthy Subjects
Authors: Álvares, Thiago S.; Meirelles, Cláudia M.; Bhambhani, Yaagesh N.; Paschoalin, Vânia M.F.; Gomes, Paulo S.C.
Friday, April 8, 2011
Kiichiro Yano, Lawrence F. Brown,2 and Michael Detmar
Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA2Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA
Received September 12, 2000; Accepted January 11, 2001.
The murine hair follicle undergoes pronounced cyclic expansion and regression, leading to rapidly changing demands for its vascular support. Our study aimed to quantify the cyclic changes of perifollicular vascularization and to characterize the biological role of VEGF for hair growth, angiogenesis, and follicle cycling. We found a significant increase in perifollicular vascularization during the growth phase (anagen) of the hair cycle, followed by regression of angiogenic blood vessels during the involution (catagen) and the resting (telogen) phase. Perifollicular angiogenesis was temporally and spatially correlated with upregulation of VEGF mRNA expression by follicular keratinocytes of the outer root sheath, but not by dermal papilla cells. Transgenic overexpression of VEGF in outer root sheath keratinocytes of hair follicles strongly induced perifollicular vascularization, resulting in accelerated hair regrowth after depilation and in increased size of hair follicles and hair shafts. Conversely, systemic treatment with a neutralizing anti-VEGF antibody led to hair growth retardation and reduced hair follicle size. No effects of VEGF treatment or VEGF blockade were observed in mouse vibrissa organ cultures, which lack a functional vascular system. These results identify VEGF as a major mediator of hair follicle growth and cycling and provide the first direct evidence that improved follicle vascularization promotes hair growth and increases hair follicle and hair size.
Full text PDF:
Antiaging treatments have been legally prescribed for approximately thirty years
Ukraintseva SV, Arbeev KG, Michalsky AI, Yashin AI.
Max Planck Institute for Demographic Research, 18057 Rostock, Germany. email@example.com
There is an interesting divergence between the achievements of geriatrics and gerontology. On the one hand, during the last 30 years physicians in many developed countries have successfully prescribed several medicines to cure various symptoms of senescence. On the other hand, the influence of such medicines on human life span practically has not been studied. The most common of the relevant medicines are nootropic piracetam, gamma-aminobutyric acid (GABA), selegiline, Ginkgo biloba, pentoxifylline, cerebrolysin, solcoseryl, ergoloid, vinpocetin, sertraline, and estrogens, among others. Available data from human clinical practices and experimental animal studies indicate that treatments with these drugs improve learning, memory, brain metabolism, and capacity. Some of these drugs increase tolerance to various stresses such as oxygen deficit and exercise, stimulate the regeneration of neurons in the old brain, and speed up the performance of mental and physical tasks. This means that modern medicine already has "antiaging" treatments at its disposal. However, the influence of such treatments on the mean and maximal life span of humans, and on the age trajectory of a human survival curve has been poorly studied. The increase in human life expectancy at birth in the second half of the last century was mostly caused by the better survival at the old and oldest old rather than at the young ages. In parallel, the consumption of brain protective and regenerative drugs has been expanding in the elderly population. We provide evidence in support of the idea that the consumption of medicines exerting antiaging properties may contribute to the increase in human longevity.
PMID: 15246996 [PubMed - indexed for MEDLINE]
Tuesday, April 5, 2011
Madalina Ionescu and Lawrence A. Frohman
Objective: Our objective was to assess GH pulsatility after a single injection of CJC-1295 and determine which GH secretion parameters correlated to the increase in IGF-I production.
Results: GH secretion was increased after CJC-1295 administration with preserved pulsatility. The frequency and magnitude of GH secretory pulses were unaltered. However, basal (trough) GH levels were markedly increased (7.5-fold; P < 0.0001) and contributed to an overall increase in GH secretion (mean GH levels, 46%; P < 0.01) and IGF-I levels (45%; P < 0.001). No significant differences were observed between the responses to the two drug doses. The IGF-I increases did not correlate with any parameters of GH secretion.
READ THE FULL ARTICLE: http://jcem.endojournals.org/cgi/content/full/91/12/4792
Tuesday, October 19, 2010
Maximum heart rate declines at high altitude, presumably due to hypoxic depression of the heart. Pentoxifylline, a Theologically active drug, increases maximum heart rate at high altitude. We tested the hypothesis that pentoxifylline increases oxygen saturation of arterial blood, which for coronary arterial blood could explain the chronotropic effect. The study was conducted in Sikkim. Twelve subjects were tested at 2100 m, 2730 m, and 4600 m altitude. In a double blind protocol, 6 subjects took pentoxifylline (1200 mg per day) each day for five weeks before and during the study. Control subjects (n=6) took a placebo. The most important finding was a significantly higher resting arterial saturation at 4600 m in the subjects taking pentoxifylline (80.7% versus 75.4% in the control group). Possible mechanisms of this action of pentoxifylline include improved pulmonary gas exchange.
Monday, October 18, 2010
Sunday, October 17, 2010
Cellulite Treatment with Mesotherapy is ideal for anyone looking to fight against dimply fat deposits and cellulite with a fast, relatively painless, non-surgical procedure. During the Mesotherapy treatment we inject a special solution (containing among other things hyaluronic acid) into the fat cells by tiny injections. After 3-4 Mesotherapy treatments the results are clear: the skin becomes flexible, tight and silky smooth; cellulite disappears.
Cellulite Treatment with Mesotherapy
Most women at some point in their lives face the problem of minor weight gain and cellulite on different parts of the body. You do not have to be overweight for cellulite to form on the thighs, buttocks, abdomen or arms; slim people are just as prone to it. Treating cellulite with mesotherapy is ideal for anyone looking to fight effectively against dimply fat deposits and cellulite with a fast, relatively painless, non-surgical procedure. During the Mesotherapy treatment we inject a special solution into the fat cells (the solution contains, among other things, hyaluronic acid). After anaesthetising the skin, we treat it in different depths depending on the problem. After 3-4 Mesotherapy treatments the results are clear: the skin becomes flexible, tight and silky smooth, cellulite disappears.
Cellulite is now considered endemic. Not only are we responsible for this, it is genetics too. There is not much we can change about this, but neither do we have to despair! Cellulite can be corrected to some degree, and with the right care and treatment it can be totally removed.
Aside from genetics, many other things are responsible for the evolution of cellulite. Fat deposits under the skin come to the surface because of water retention and other metabolic disorders, and also due to improper drainage of the lymphatic system. These deposits are left in the skin tissues, causing the skin to become spongy and take on an orange peel-like appearance. A sedentary lifestyle, an unhealthy diet, unsatisfactory liver and kidney function and disorders in the nervous and hormone system can all contribute to the development of cellulite as well.
Cellulite Treatment with Mesotherapy: Consultation
During the first consultation with your consultant, you will discuss what results you wish to achieve with the Mesotherapy treatment. Naturally your consultant will check your cellulite to see what stage it is at, and will advise as to whether Mesotherapy is the appropriate treatment for you. Your consultant can recommend various lifestyle changes, such as our OPTIMA MEDICAL DIET or liposuction, if your desired results are difficult to achieve with Mesotherapy sessions alone.
During the consultation you will talk about your current lifestyle, what you have to ensure during the treatment, and how to maintain results after the treatment. Before the Mesotherapy treatment we also give you some ‘vacuum therapy’, which stimulates blood circulation and the lymphatic system, which in turn speeds up the destruction of the loose fat cells, thereby increasing absorption of the special solution removing cellulite.
Cellulite Treatment with Mesotherapy: The Solution and How It Works
The purpose of Mesotherapy is to regenerate skin tissue, to make it more flexible and to remove cellulite. We use a special solution for Mesotherapy; its main components are hyaluronic acid, caffeine and other trace elements. Hyaluronic acid can be found in the human body as a connective tissue: it retains water and fights effectively against free radicals. Caffeine breaks down fat molecules and helps triglycerides to dissolve fatty acids. Zinc, cobalt and manganese are three examples of the trace elements: these add to cell regeneration and speed up the metabolism.
Cellulite treatment with Mesotherapy is effective due to the fact that we inject the solution directly into the relevant area. Conventional creams cannot reach these depths. The components of the Mesotherapy solution activate fat decomposition, speed up the metabolism, and improve cell regeneration so cellulite can be removed.
Cellulite Treatment with Mesotherapy: The Technique
The treatment is carried out using a special Mesotherapy gun, which contains a tiny sterile needle that injects the solution into the skin.
We choose an appropriate solution for the skin and inject it approx. 6-10mm into the skin. Injections are made 1 - 1.5cm apart.
Cellulite Treatment with Mesotherapy: The treatment
If after your consultation you are found to be suitable for the Mesotherapy treatment and want to start, you can make an appointment immediately.
Cellulite is treated with Mesotherapy over a course of eight sessions. One session lasts approx. 1 hour, and you can have the Mesotherapy treatment weekly. We always begin a session by sterilizing and, if necessary, anaesthetizing the chosen area.
The solution is injected into the fat tissue using a tiny needle. The solution fights against the root causes of cellulite: residual decomposition products and swollen fat cells. You will only feel minimal discomfort after the Mesotherapy treatment. The skin can go red, but this will pass in 2-3 days. At the end of the treatment we apply a vitamin K cream onto the skin. We advise you to moisturise and massage your skin daily. Avoid sunlight and solariums while having the Mesotherapy treatment.
Cellulite Treatment with Mesotherapy: Aftercare
The course of treatment takes 2 months, and visible results can be seen after 4-6 sessions: the surface of the skin is firmer, bulges are less apparent. The final results appear at the end of the treatment - our clients lose up to 3-4 centimetres in diameter (e.g. on thighs). The treatment can be repeated annually even before cellulite appears again.
Friday, October 15, 2010
Besides being a skin conditioning active ingredient it is also well known for its anti-cellulite properties, as well as a fat combustion booster. L - Carnitine is like a fat (fatty acids) transporter since it helps to pass the Acyl-CoA into the mitochondrial matrix, which is supposed to be impermeable to Acyl-CoA. The process would be the next: 1. The enzyme carnitine palmitoyltransferase I (CPTI) from the external mitochondrial membrane eliminates the coenzyme A from the Acyl-CoA while attaches it to the L- Carnitine placed within the intermembrane space, producing Acyl Carnitine; the CoA remains free within the cellular cytoplasm in order to activate another fatty acid. 2. Then, a transporter protein know as translocase of the inner membrane, transfers the Acyl Carnitine to the z while the carnitine palmitoyltransferase II (CPTII) joints a CoA molecule from the fatty acid matrix, and therefore regenerating the Acyl-CoA. 3. L- Carnitine returns to the place between the membranes trough the transporter protein and reacts with the other Acyl-CoA, repeating the whole cycle. L -Carnitine helps the degradation of the triglycerides within the mitochondrias and cellular organelles responsible of that trough the cellular transport. This way the metabolism is boosted and the fat combustion generating heat over the area treated.
Apply this cosmetic treatment to the parts of the body targeted where is present the cellulite and localized fatty spots within cold areas since it increases the basal metabolism generating an increase of the temperature.
Thursday, October 14, 2010
GSH glutathione, the master antioxidant (Tationil, TAD600, Ridutox) - skin smoothing-glowing-whitening, cellular rejuvenation
- it is a protein (amino acid) molecule which is important as our body antioxidant, immune system booster and detoxifier
- it presents in every cell to promote normal function as maintaining the immune system
- one of the master antioxidant that mostly found in liver
- it eliminates toxic compound (such as Paracetamol) in liver
- it reconstitutes vitamin C and E which is being oxidized
- combine taking with vitamin c injection greatly enhance your immunity, reduces tiredness, more youthful skin and stay healthy
- fights against the cancer, heart disease, premature aging, autoimmune disease and chronic illness
Dosage and method: 1-3 ampoules weekly by intravenous or intramuscular method.
Frequently Asked Questions:
1. What is glutathione? It is an important chemical that acts as a powerful antioxidant to preserve and protect the brain and other body tissues by protecting them from the damage of free radicals. It also acts to recycle vitamin C & E which also reduce free radicals.
2. What studies prove it work or are there any studies that prove it works?
The landmark study was done by the Department of Neurology, University of Sassari, Italy in 1996. In this study all patients improved significantly after glutathione therapy with a 42% decline in disability.
3. What is glutathione used for? It has been used to treat all symptoms of neurodegenerative diseases such as Parkinson's, Alzheimer's, multiple sclerosis, stroke, ALS, irritable bowel, and chronic fatigue.
4. What improvement in symptoms can one expect? Many patients have had profound improvements with respect to reduction of rigidity, increased mobility, improved ability to speak, less depression, and decreased tremor. Glutathione has the added benefit of protecting the brain from free radical damage, thus possibly slowing the progression of the underlying illness.
5. How long can a person take glutathione and how long will the effect last after I stop using it? It can be taken permanently. In the 1996 Italian study the therapeutic effect lasted 2-4 months after therapy was stopped.
6. How long has this treatment been used. Physicians have been using glutathione infusions for at least 30 years, probably longer.
7. How is the treatment given? It is given intravenously in the arm by IV push over 10 to 15 minutes usually three times a week in a physician's office.
Also available as 5 ml amps for injection
General: Pentoxifylline increases red blood cell deformability, reduces blood viscosity and decreases the potential for platelet aggregation and thrombus formation. Used to treat high altitude sickness. It is a member of xanthine family, similar to caffeine and is a potent PDE inhibitor, thus it helps burning fat
Effect: As a vasodilator it improves blood flow through blood vessels and therefore helps with blood circulation in the arms and legs. Used for neuropathic injuries and it also helps prevent strokes, can be used in managing sickle cell anemia and improves blood flow to the brain. In the lungs, pentoxifylline inhibits TNF-alpha production from human alveolar macrophages. It is competitive nonselective phosphodiesterase inhibitor which raises intracellular cAMP, activates PKA, inhibits TNF-alpha and leukotriene synthesis, and reduces inflammation and innate immunity, nonselective adenosine receptor antagonist.
Use: 400 mg SR 1-3 times daily. Interactions: anti-coagulants, theophylline. Pentoxifylline and sodium thiopental causes death by acute pulmonary oedema in rats. Nausea, hypotension.
Sports Performance: Reportedly used orally 1-3 times daily to cope with elevated hematocrit level. Possibly increases oxygen transport and delivery to muscles and within aveoli of lung. Mild blood thinner and vasodilator.
Legality: Pentoxifylline is not currently banned by any sporting governing body.
Investigation of the effects of oral supplementation of arginine in the increase of muscular strength and mass
1, Turibio Leite de Barros1, Daniel Furquim Leite de Barros2 and Marcelo Lima3
FULL PDF article DOWNLOAD
Introduction: Oral administration of arginine has been associated with physical performance improvement due to probable decrease of muscular fatigue derived from the vasodilatation factor of the nitric oxide over the skeletal muscles.
Objective: to evaluate the effects of oral administration of L-Arginine during an exercise program with weights. Methods: 20 male individuals, randomly divided in two groups: A and B, were submitted to eight weeks of training with weights (three times per week). Group A used 3 grams of L-Arginine + vitamin C during the eight weeks and group B used only vitamin C (control group).
Results: After eight weeks of training, group A presented body weight values and lean mass significantly higher (p < 0.05), body fat percentage significantly lower (p< 0.05), and strength of lower limbs significantly higher (p < 0.05), while group B did not present significant differences for the same period.
Conclusion: Oral administration of arginine associated with a training program with weights increased the stimuli of the exercise to the skeletal muscles level, enabling hence, increase of
muscular strength and mass.
Wednesday, October 13, 2010
Vinpocetine is a periwinkle plant extract (Vinca major) that improves brain function. It has been used medicinally in Europe since 1983. Vinpocetine dilates the arteries of the brain, decreases platelate aggregation, and increases erythrocyte flexibility, all of which are beneficial in cerebrovascular disease. By increasing the brain's utilization of oxygen and oxygen, vinpocetine increases cerebral metabolic rate. Vinpocetine can help prevent stroke and can prevent much of the damage that occurs following stroke if administered immediately following stroke.
· dilates the arteries of the brain but does not dilate other blood vessels.
· can prevent the occurrence of stroke and can prevent much of the damage if administered immediately following stroke.
· improves circulation within the brain (i.e. it alleviates cerebral insufficiency).
· increases Adenosine Triphosphate (ATP) within the brain's neurons.
· improves the brain's utilization of glucose.
· can alleviate headaches.
· accelerates the rate of learning by 40% (in animal research).
· improves memory. Healthy subjects exhibited significant short-term memory improvement 1 hour after taking 40 mg of Vinpocetine (62%).
· increases the length of time that short-term memory is retained.
· can block the action of drugs that disrupt memory.
· improves the brain's utilization of Oxygen and increases the resistance of Neurons to the damage that would otherwise be caused by Hypoxia.
· can alleviate speech impairment.
· improves circulation to the eyes thereby improving vision and eyesight disorders.
· improves impaired hearing and improves many inner-ear problems.
· improves Tinnitus (ringing in the ears).
· improved the vertigo (dizziness) of 77% of the patients in one study.
· reduces menopausal symptoms.
· increases the brain's turnover of Serotonin and Norepinephrine.
· improves the flexibility of red blood cells and may thereby help to prevent strokes.
· alleviates insomnia and several types of sleep disorders.
Piracetam - the original nootropic
by James South MA
Piracetam (technically known as 2-oxo-pyrrolidone) was developed in the mid-1960's by UCB pharmaceutical company of Belgium. It was originally used to treat motion sickness. (1) Between 1968 and 1972, however, there was an explosion of Piracetam research which uncovered its ability to facilitate learning, prevent amnesia induced by hypoxia and electroshock, and accelerate electroencephalograph return to normal in hypoxic animals. (1) By 1972 700 papers were published on Piracetam. (1) Yet already by 1972 Piracetam's pharmacologic uniqueness led C.E. Giurgea, UCB's principal Piracetam researcher and research coordinator, to formulate an entirely new category of drugs to describe Piracetam: the nootropic drug. (2)
According to Giurgea, nootropic drugs should have the following characteristics:
1) they should enhance learning and memory.
2) They should enhance the resistance of learned behaviors/memories to conditions which tend to disrupt them (e.g. electroconvulsive shock, hypoxia).
3) They should protect the brain against various physical or chemical injuries (e.g. barbiturates, scopalamine).
5) They should ''increase the efficacy of the tonic cortical/subcortical control mechanisms."
6) They should lack the usual pharmacology of other psychotropic drugs (e.g. sedation, motor stimulation) and possess very few side effects and extremely low toxicity. (3)
As research into Piracetam and other nootropics (e.g. pyritinol, centrophenoxine, oxiracetam, idebenone) progressed over the past 30 years, section 5) of Giurgea's original definition has been gradually dropped by most researchers. (3) Nonetheless, the nootropic drugs represent a unique class of drugs, with their broad cognition enhancing, brain protecting and low toxicity/ side effect profiles. It is an interesting comment on the AMA/FDA stranglehold on American medicine that as of January 2001, not a single nootropic drug has ever been given FDA approval for use in the U.S.
Piracetam has been used experimentally or clinically to treat a wide range of diseases and conditions, primarily in Europe. (Although much of the research on Piracetam has been published in English, a large amount of Piracetam research has been published in German, French, Italian, and Russian.)
Piracetam has been used successfully to treat alcoholisrn/ alcohol withdrawal syndrome in animals and man. (4,5,19) Piracetam has brought improvement, or slowed deterioration, in "senile involution" dementia and Alzheimer’s disease. (6,7) Piracetam has improved recovery from aphasia (speech impairment) after stroke. (8) Piracetam has restored various functions (use of limbs, speech, EEC, slate of consciousness) in people suffering from acute and chronic cerebral ischemia (decreased brain blood flow). (9,10) Piracetam has improved alertness, co-operation, socialization, and IQ in elderly psychiatric patients suffering from "mild diffuse cerebral impairment." (11)
Piracetam has increased reading comprehension and accuracy in dyslexic children. (8,12) Piracetam increased memory and verbal learning in dyslexic children, as well as speed and accuracy of reading, writing and spelling. (13,14) Piracetam potentiated the anticonvulsant action of various anti-epileptic drugs in both animals and man, while also eliminating cognitive deficits induced by anti-epileptic drugs in humans. (15,16) Piracetam has improved mental performance in "aging, nondeteriorated individuals" suffering only from "middle-aged forgetfulness." (17) Elderly outpatients suffering from "age-associated memory impairment" given Piracetam showed significant improvement in memory consolidation and recall. (8) Piracetam reversed typical EEC slowing associated with "normal" and pathological human aging, increasing alpha and beta (fast) electroencephalograph activity and reducing delta and theta (slow) electroencephalograph activity, while simultaneously increasing vigilance, attention and memory. (17A)
Piracetam reduced the severity and occurrence of major symptoms of "post-concussional syndrome," such as headache, vertigo, fatigue and decreased alertness (18), while it also improved the state of consciousness in deeply comatose hospitalized patients following head injuries. (19) Piracetam has successfully treated motion sickness and vertigo. (1) Piracetam "is one of the best available drugs for treating myoclonus [severe muscle spasms] of cortical origin." (20) Piracetam has successfully treated Raynaud's syndrome (severe vasospasm in hands and/or feet), with "a rapid and marked improvement. The efficacy of Piracetam has been maintained in several patients already followed for 2-3 years." (21) Piracetam has been used to inhibit sickle cell anemia, both clinically and experimentally. (11) Piracetam has improved Parkinson's disease, and may synergize with standard L-dopa treatment. (1) A key part of Piracetam's specialness is its amazing lack of toxicity. Piracetam has been studied in a wide range of animals: goldfish, mice, rats, guinea pigs, rabbits, cats, clogs, marmosets, monkeys, and humans. (1,19) In acute toxicity studies that attempted to determine Piracetam's "LD50" (the lethal dose which kills 50% of test animals), Piracetam failed to achieve an LD50 when given to rats intravenously at 8gm/kg bodyweight. (1) Similarly, oral LD50 studies in mice, rats, and dogs given 10gm Piracetam/kg bodyweight also produced no LD50! (1) This would he mathematically equivalent to giving a 70 kg (154 pound) person 700gm (1.54 pounds) of Piracetam! As Tacconi and Wurtman note, ''Piracetam apparently is virtually non-toxic. Rats treated chronically with 100 to 1,000 mg/kg orally for 6 months and dogs treated with as much as 10g/kg orally for 1 year did not show any toxic effect. No teratogenic (birth deformity) effects were found, nor was behavioral tolerance noted." (22) Thus, Piracetam must be considered one of the toxicologically safest drugs ever developed.
From the earliest days of Piracetam research, the ability of Piracetam to partly or completely prevent or reverse the toxic action of a broad array of chemicals and conditions has been repeatedly demonstrated. Paula-Barbosa and colleagues discovered that long-term (12 month) alcohol-feeding to rats significantly increased formation of lipofuscin (an age-related waste pigment) in brain cells. Giving high dose Piracetam to the alcohol-fed rats reduced their lipofuscin levels significantly below both the control and alcohol/no Piracetam rats' levels. (4) Piracetam antagonized the normally lethal neuromuscular blockade (which halts breathing) induced by mice by intravenous hemicholinium-3 (HC-3) (23), and Piracetam also blocked the lethal neuromuscular blockade induced in cats by d-tubocurarine. (1) Piracetam reversed learning and memory deficits in mice caused by the anti-cholinergic substance, HC-3. (23) When mice were given oxydipentonilim, a short-acting curare-like agent which halts breathing, at a dose sufficient to kill 90% of one group and 100% of another group of placebo-treated controls, the two groups of Piracetam-treated mice had a 90% and 100% survival rate. (19)
Rapid synthesis of new protein in brain cells is required for memory formation. Piracetam has ameliorated the amnesia induced by rodents by cycloheximide, a protein synthesis inhibitor. (1)
Hexachlorophene is a toxic chemical that induces edema, membrane damage, and increased sodium /decreased potassium in brain cells. (Hexachlorophene was used in shampoos, soaps and other personal care products until about a decade ago.) Rats were fed hexachlorophene orally for 3 weeks, then given Piracetam or one of 5 other drugs by injection for 6 days. Hexachlorophene seriously disrupted the rats' ability to navigate a horizontal ladder without frequently falling off the rungs. Piracetam reduced the fall rate 75% compared to saline-injected controls on the first day of treatment. None of the other drugs came close to that improvement. (24)
Piracetam increases the survival rate of rats subjected to severe hypoxia. (1,25) When mice, rats and rabbits have been put under diverse experimental hypoxic (low oxygen) conditions, Piracetam has acted to attenuate or reverse the hypoxia-induced amnesia and learning difficulties, while speeding up post-hypoxic recovery time and reducing time to renormalize the EEC}. (1,2,25) When a single 2400mg dose of Piracetam was given to humans tested under 10.5% oxygen (equivalent to 5300m./17,000 ft. altitude), eye movement reflexes were enhanced, while breathing rate and choice reaction time were reduced by Piracetam. (26)
Electro convulsive shock (electro convulsive shock) is a powerful disruptor of learning and memory. When a group of rats were taught to avoid a dark cubicle within their cage there was 100% retention of the learned behavior 24 hours later.
Giving a maximal electro convulsive shock right after learning caused the learning-retention rate to drop lo 20% 24 hours later in the control group, while Piracetam-treated electro convulsive shock rats still had a 100% retention of the avoidance behavior 24 hours later. (2) Other experiments with mice and rats show Piracetam's ability to attenuate or reverse electro convulsive shock-induced amnesia. (19.27)
When given the fast acting barbiturate secobarbital, combined with Piracetam injected 1 hour before the secobarbital, 10 of 10 rabbits survived, with only minimal abnormalities in their electroencephalograph records. The electroencephalograph records the electrical activity of large groups of corticol neurons, and also reflects cerebral oxygen/glucose metabolism and blood flow. (25)
Only 3 of 10 rabbits given) secobarbital with saline injection survived, and most of that groups' electroencephalograph records showed rapid onset of electrical silence, followed quickly by death. When secobarbital was given to rabbits combined with oral Piracetam, 8 of 9 survived, with only 3 of 9 saline-fed controls surviving. The electroencephalograph records of both groups were similar to those of the rabbits given i.v. Piracetam and saline. (28)
By the 1980s neuroscientists had discovered that brain cholinergic neural networks, especially in the cortex and hippocampus, are intimately involved in memory and learning. Normal and pathological brain aging, as well as Alzheimer's-type dementia were also discovered lo involve degeneration of both the structure and function of cholinergic nerves, with consequent impairment of memory and learning ability. (29)
During this same period a growing body of evidence began to show that Piracetam works in part through a multimodal cholinergic activity. Studies with both aged rats and humans which combined Piracetam with either choline or lecithin (phosphatidyl choline), found radically enhanced learning abilities in rats, and produced significant improvement in memory in Alzheimer’s patients. (30-35)
Yet giving choline or lecithin alone (they are precursors for the neurotransmitter acetylcholine) in these studies provided little or no benefit, while Piracetam alone provided only modest benefit.
Animal research has also shown that Piracetam increases high-affinity choline uptake, a process that occurs in cholinergic nerve endings which facilitates acetylcholine formation. (23,29) "High-affinity choline uptake rate has been shown to be directly coupled to the impulse flow through the cholinergic nerve endings and it is a good indicator of acetylcholine utilization nootropic drugs (including Piracetam) activate brain cholinergic neurons" (29) HC-3 induces both amnesia and death through blocking high-affinity choline uptake in the brain an din peripheral nerves that control breathing. Since Piracetam blocks HC-3 asphyxiation death and amnesia, this is further evidence of Piracetam's pro-high-affinity choline uptake actions. (23,29)
Scopalamine is a drug that blockades acetylcholine receptors and disrupts energy metabolism in cholinergic nerves. When rats were given Scopalamine, it prevented the learning of a passive avoidance task, and reduced glucose utilization in key cholinergic brain areas. When rats given Scopalamine were pretreated with 100/kg Piracetam, their learning performance became almost identical to rats not given Scopalamine. (36) The Piracetam treatment also reduced the Scopalamine depression of glucose-energy metabolism in the rats' hippocampus and anterior cingulate cortex, key areas of nerve damage and glucose metabolism reduction in Alzheimer’s disease.(36)
German researchers added to the picture of Piracetam's cholinergic effects in 1988 and 1991. Treatment for 2 weeks with high dose oral Piracetam in aged mice elevated the density of frontal cortex acetylcholine receptors 30-40%, restoring the levels to those of healthy young mice. A similar decline in cortex acetylcholine receptors occurs in "normal" aging in humans. (37) The same group of researchers then discovered that there is a serious decline in the functional activity of acetylcholine receptors in aged mice; with many receptors becoming "desensitized" and inactive. Oral treatment with high dose Piracetam also partially restored the activity of acetylcholine cortex nerves, as measured by the release of their "second messenger," inositol-1-phosphate. (38)
Glutamic acid (glutamate) is the chief excitatory neurotransmitter in the mammalian brain. Piracetam has little affinity for glutamate (glutamate) receptors, yet it does have various effects on glutamate neurotransmission. One subtype of glutamate receptor is the AMPA receptor. Micromolar amounts [levels which are achieved through oral Piracetam intake] of Piracetam enhance the efficacy of AMPA-induced calcium influx [which "excites" nerve cells to fire] in cerebeller [brain] cells. Piracetam also increases the maximal density of [AMPA glutamate receptors] in synaptic membranes from rat cortex due to the recruitment of a subset of AMPA receptors which do not normally contribute to synaptic transmission." (1) Further support for involvement of the glutamate system in Piracetam's action is provided by a Chinese study which showed that the memory improving properties of Piracetam can be inhibited by ketamine, an NMDA (another major subtype of glutamate receptor) channel blocker. (1) Furthermore, high dose injected Piracetam decreases mouse brain glutamate content and the glutamate/GABA ratio, indicating an increase in excitatory nerve activity (1)
At micrornolar levels, Piracetam potentiates potassium-induced release of glutamate from rat hippocampal nerves. (1)
Given that acetylcholine and glutamate are two of the most central "activating" neurotransmitters and the facilatory effects of acetylcholine/glutamate neural systems on alertness, focus, attention, memory and learning. Piracetam’s effects on acetylcholine/glutamate neurotransmission must he presumed to play a major role in its demonstrated ability to improve mental performance and memory. Although Piracetam is generally reported to have minimal or no side effects, it is interesting to note that Piracetam’s occasionally reported side effects of anxiety, insomnia, agitation, irritability and tremor (18) are identical to the symptoms of excess acetylcholine/glutamate neuroactivity.
In spite of the many and diverse neurological/psychological effects Piracetam has shown in human, animal and cell studies, Piracetam is generally NOT considered to he a significant agonist (direct activator) or inhibitor of the synaptic action of most neurotransmitters. Thus, major nootropic researchers Pepeu and Spignoli report that "the pyrrolidinone derivatives [Piracetam and other racetams] show little or no affinity for central nervous system receptors for dopamine, glutamate; serotonin, GABA or benzodiazepine." (23) They also note however that "a number of investigations on the electrophysiological actions of nootropic drugs have been carried out. Taken together, these findings indicate that the nootropic drugs of the [Piracetam-type] enhance neuronal excitability [electrical activity] within specific neuronal pathways." (23)
Grau and colleagues note that "there exist papers giving data of bioelectric activity as affected by Piracetam, and suggesting that it acts as a non-specific activator of the excitability. [i.e. brain electrical activity] thus optimizing the functional state of the brain." (25)
Gouliaev and Senning similarly state "we think that the racetams exert their effect on some species [of molecule] present in the cell membrane of all excitable cells, i.e. the ion carriers or ion channels and that they somehow accomplish an increase in the excitatory (electrical) response. It would therefore seem that the racetams act as potentiators of an already present activity (also causing the increase in glucose utilization observed), rather than possessing any [neurotransmitter-like] activity of their own, in keeping with their very low toxicity and lack of serious side effects. The result of their action is therefore an increase in general neuronal sensitivity toward stimulation." (1)
Thus Piracetam is NOT prone to the often serious side effects of drugs which directly amplify or inhibit neurotransmitter action e.g. MAO inhibitors; Prozac® style "selective serotonin reuptake inhibitors", tricyclic antidepressants, amphetamines, Ritalin®, benzodiazepines (Valium), etc.
A key finding on Piracetam in various studies is its ability to enhance brain energy, especially under deficit conditions. Energy (ATP) is critical to the brain's very survival; it typically uses 15-20% of the body's total ATP production, while weighing only 2-3% or so of bodyweight. Brain cells must produce all their own ATP from glucose (sugar) and oxygen - they cannot "borrow" ATP from other cells. Branconnier has observed that "evidence from studies of cerebral blood flow, oxygen uptake and glucose utilization have shown that brain carbohydrate metabolism is impaired in a variety of dementias and that the degree of reduction in brain carbohydrate metabolism is correlated with the severity of the dementia." (39) In a 1987 study, Grau and co-workers gave saline or Piracetam i.v. to rats who were also fed i.v. radioactive deoxygilicose to help measure brain metabolism. Compared to saline controls, Piracetam rats had a 22% increase in whole brain glucose metabolism, while the increase in 12 different brain regions ranged from L6 to 28%. (25) This increase in brain energy metabolism occurred under normal oxygen conditions.
In 1976 Nickolson and Wolthuis discovered that Piracetam increased the activity of adenylate kinase in rat brain. Adenylate kinase is a key energy metabolism enzyme that converts ADP into ATP and AMP and vice versa. It comes into play especially when low brain oxygen begins to reduce mitochondrial ATP production. As existing ATP is used up, ADP is formed. Under the influence of adenylate kinase, 2ADP becomes ATP plus AMP. Thus Piracetam-activated adenylate kinase can slow down the drop in ATP in oxygen-compromised brains. This helps explain Piracetam’s ability to prevent abnormalities in animals subjected to hypoxia or barbiturates. When oxygen levels return toward normal, adenylate kinase can convert AMP into ADP, which can then be used in the reactivated mitochondria to make more ATP. This accounts for the ability of Piracetam to speed up recovery from hypoxia seen in animal studies. (40)
In their 1987 study with rats, Piercey and colleagues found that Piracetam could restore scopalamine depressed energy metabolism modestly in many brain areas, and significantly in the hippocampus and anterior cingulate cortex. (36)
Piracetam has also been shown to increase synthesis and turnover of cytochrome b5, a key component of the electron transport chain, wherein most ATP energy is produced in mitochondria. (22) Piracetam also increases permeability of mitochondrial membranes for certain intermediaries of the Krebs cycle, a further plus for brain ATP production. (25) In his 1989 paper on cerebral ischemia in humans, Herrschaft notes that the Herman Federal Health Office has conducted controlled studies that indicate a "'significant positive" effect of Piracetam (4.8 - 6gm/day) to increase cerebral blood flow, cerebral oxygen usage metabolic rate and cerebral glucose metabolic rate in chronic impaired human brain function - i.e. multi-infarct dementia, senile dementia of the Alzheimer type, and pseudo-dementia. (9)
The cerebral cortex in humans and animals is divided into two hemispheres, the left and right cortex. In most humans the left hemisphere (which controls the right side of the body) is the language center, as well as the dominant hemisphere. The left cortex will tend to be logical, analytical, linguistic and sequential in its information processing, while the right cortex will usually be intuitive, holistic, picture-oriented and simultaneous in its information processing.
Research has shown that most people favor one hemisphere over the other, with the dominant hemisphere being more electrically active and the non-dominant hemisphere relatively more electrically silent, when a person is being tested or asked to solve problems or respond to information. The two cortical hemispheres are linked by a bundle of nerve fibers: the corpus callosum and the anterior commisure. In theory these two structures should unite the function of the two hemispheres. In practice they act more like a wall separating them.
From a neurological perspective, the cerebral basis for a well-functioning mind would he the effective, complementary, simultaneous integrated function of both cortical hemispheres, with neither hemisphere being automatically or permanently dominant. This in turn would require the corpus callosum and cerebral commisure to optimize information flow between the two hemispheres. Research has shown Piracetam to facilitate such inter-cerebral information transfer-indeed, it's part of the definition of a "nootropic drug."
Giurgea and Moyersoons reported in 1972 that Piracetam increased by 25 to 100% the transcallosal evoked responses elicited in cats by stimulation of one hemisphere and recorded from a symmetrical region of the other hemisphere. (41) Buresova and Bures, in a complex series of experiments involving monocular (one-eye) learning in rats, demonstrated that "Piracetarn enhances transcommisural encoding mechanisms and some forms of inter-hemispheric transfer." (42)
Dimond and co-workers used a technique called "dichotic listening" to verily the ability of Piracetam to promote interhemispheric transfer in humans. In a dichotic listening test, different words are transmitted simultaneously into each ear by headphone. In most people the speech center is the left cortex. Because the nerves from the ears cross over to the opposite side of the brain, most people will recall more of the words presented to the right ear than the left ear. This occurs because words received by the right ear directly reach the left cortex speech center, while words presented to the left ear must reach the left cortex speech center indirectly, by crossing the corpus callosum from the right cortex. Dimond's research with healthy young volunteers showed that Piracetam significantly improved left ear word recall, indicating Piracetam increased interhemispheric transfer. (43)
Okuyama and Aihara tested the effect of aniracetam, a Piracetam analog, on the transcallosal response of anaesthetised rats. The transcallosal response was recorded from the surface of the frontal cortex following stimulation of the corresponding site on the opposite cortical hemisphere. The researchers reported that "the present results indicate that Piracetam...increased the amplitude of the negative wave, thereby facilitating inter-hemispheric transfer. Thus, it is considered that the functional increase in interhemispheric neuro-transmission by nootropic drugs may be related to the improvement of the cognitive function [that nootropics such as Piracetam and aniracetam promote]." (44)
The notable absence of biochemical, physiological, neurological or psychological side effects, even with high dose and/or long-term Piracetam use, is routinely attested to in the Piracetam literature. Thus in their 1977 review Giurgea and Salama point out: "Piracetam is devoid of usual 'routine' pharmacologic activities [negative side effects] even in high doses. In normal subjects no side effects or 'doping' effects were ever observed. Nor did Piracetam induce any sedation, tranquilization, locomotor stimulation or psychodysleptic symptomatology." (19) Wilshen and colleagues, in their study on 225 dyslexic children, note that "Piracetam was well tolerated, with no serious adverse clinical or laboratory effects reported." (12) In this particular study (as in many others), the incidence of (mild) side effects was higher in the placebo group than in the Piracetam group! In his 1972 8 week study on 196 patients with "senile involution" dementia, Stegink reported that "No adverse side effects of Piracetam [2.4gm/day] were reported." (6) In their study of 30 patients treated for one year with 8gm Piracetam/day, Croisile and colleagues observed that "Few side effects occurred during the course of the study - one case of constipation in the Piracetam group.... Piracetam had no effect on vital signs, and routine tests of renal, hepatic, and hematological functions remained normal. No significant changes in weight, heart rate, or blood pressure occurred...." (7)
Yet as noted in the section on glutamate, because Piracetam is a cholinergic/glutamatergic activator, there is the potential for symptoms related to cholinergic/glutamatergic excess to occur, especially in those unusually sensitive to Piracetam. Such symptoms - anxiety, insomnia, irritability, headache, agitation, nervousness, and tremor - are occasionally reported in some people taking Piracetam. (11,18) Reducing dosage, or taking magnesium supplements (300-500mg/day), which reduce neural activity, will frequently alleviate such "overstimulation" effects. Persons consuming large amounts of MSG (monosodium glutamate) and/or aspartame in their diet should be cautious in using Piracetam, as should those who are highly sensitive to MSG-laden food (the "Chinese restaurant syndrome"). Caffeine also potentiates Piracetam's effects, as do other nootropics such as deprenyl, idebenone, vinpocetine, and centrophenoxine, and it may be necessary to use Piracetam in a lower dosage range if also using any of these drugs regularly. Those wishing to augment Piracetam's cholinergic effects may wish to combine it with cyprodenate or centrophenoxine, which are much more powerful acetylcholine enhancers than choline or lecithin.B complex vitamins, NADH, lipoic acid, Co Q10, or idebenone, and magnesium will enhance Piracetam's brain energy effects. In the clinical literature on Piracetam, dosages have ranged from 2.4 gm/day (6,11) up to 8gm/day (7,21), continued for years (7,21). Piracetam has a relatively short half-life in the blood, although there is some short-term bioaccumulation in the brain. (1,22) Piracetam is therefore usually taken 3-4 times daily. 1.6 gm, 3 times daily, or 1.2 gm 3-4 times daily is a fairly typical Piracetam dosage, although some people report noticeable improvement in memory and cognition from just 1.2 gm twice daily.