5-HTP

About 5-HTP

5-HTP (5-hydroxy-L-tryptophan) is the substance that the brain uses to make serotonin -- a neurotransmitter that regulates emotions, sleep-wake cycles, appetite, and general feelings of well-being.¹

When the body's serotonin levels are inadequate, the result can be depression, excessive eating, and sleep disorders. Serotonin deficiencies may also play a role in migraine headaches, fibromyalgia, panic attacks, delirium tremens, sleep terrors, and coughing.

General remarks

A good, brief summary of 5-HTP as a treatment for various conditions is the one by Birdsall in the abstract to his 1998 review.¹ A more detailed summary is the one provided by Thorne Research, Inc.²

Most, if not all, studies of 5-HTP as medical treatments are based on the concept that the underlying medical conditions involve serotonin. The treatments depend on the fact that 5-HTP crosses the blood-brain barrier and is then converted into serotonin.

Although many physicians believe that 5-HTP supplementation will not raise serotonin levels unless combined with a drug like carbidopa -- to prevent 5-HTP from being metabolized before it reaches the nervous system -- this notion has been refuted by experiments with oral 5-HTP in both rats and humans. When used orally, without the aid of other drugs, 5-HTP does significantly raise serotonin levels in the brain.³

On the other hand, it has been suggested that the metabolism of 5-HTP outside the brain may be accelerated if 5-HTP is used in combination with vitamin B6.²¹ Little has been done to examine this issue, so to be on the safe side, it would make sense to avoid B6 supplements on days when one is using 5-HTP.

The dosages of 5-HTP used in most clinical trials range from 100 mg/day in children to as much as 400 mg/day in adults. These daily dosages are usually divided into three spaced doses about 8 hours apart. The exception is in the use of 5-HTP for insomnia, where the daily dosage is taken all at once, before bedtime. Clinicians usually design 5-HTP regimens that start with a ramping-up period, using smaller doses for two weeks.²

5-HTP is well absorbed whether it is taken with food or by itself.²

5-HTP and depression

5-HTP has been of interest as an antidepressant for several decades. It has shown good results in a number of clinical trials, and given null results in others.⁴ A meta-analysis done on this medical literature in 2002 resulted in a claim that all of the clinical trials published up to that time were of poor quality and allowed no conclusions to be drawn.⁵ On the other hand, critics of such meta-analyses say that these analyses are the products of extreme and obsessive statistical finickiness and that they 'throw the baby out with the bathwater'.

It is true, in any case, that clinical studies and very large numbers of anecdotal reports attest to the effectiveness of 5-HTP as an antidepressant in some people. (The same can be said of prescription antidepressants, such as fluoxetine (Prozac) and paroxetine (Paxil) -- they are effective for some, and ineffective for others. Patients often have to try a series of these drugs before finding one that works.)

5-HTP and appetite

The ability of 5-HTP to inhibit appetite was first noted in rats in 1964.⁶ The mechanism appears to involve the raising of serotonin levels. Several dozen research papers on the subject have appeared since then, including a few reports of clinical trials both in diabetic patients and in obese patients without diabetes,^7,8 with the result that 5-HTP is widely regarded as effective in reducing the appetite and bodyweight of people who overeat.⁴ Nevertheless, the medical profession has preferred much more expensive treatments with prescription drugs, some of which have proved to be harmful to patients.⁹

5-HTP and sleep disorders

The effects of 5-HTP on sleep date from 1971,¹⁰ when it was studied as a treatment for insomnia. Despite the encouraging results of early studies,^2,11 and countless positive anecdotal reports over the years, medical research has almost completely ignored it as an insomnia treatment.

In a clinical trial in 2004 researchers reported that 5-HTP is a very effective treatment for sleep terrors in children.¹² After six months, 84% of the patients who used 5-HTP at 2 mg/kg were free of sleep terrors, as compared with only 28% of the comparison group. Sleep terrors (a.k.a. 'night terrors') are a type of nightmare from which it is difficult to awaken.¹³

5-HTP and fibromyalgia

Fibromyalgia is an ailment characterized by musculoskeletal pain (both diffuse and localized), fatigue, lowered pain thresholds, and nonrestorative sleep. Multiple lines of evidence suggest that a decline in serotonin production may be involved.¹⁴ Clinical trials in fibromyalgia patients in the early 1990s demonstrated significantly lessened symptoms.^15,16 Since that time, little or no research work has been done to follow up on these promising leads.

5-HTP and migraine

5-HTP was first reported to improve migraine headaches in the early 1970s.¹⁷ Since then, several dozen reports have been published on the subject, and almost a dozen clinical trials have been conducted -- most of them showing some efficacy of 5-HTP for prevention of migraines and other headaches.² Dosages ranged from 100 mg/day in children to 400 mg/day in adults, in divided doses.

5-HTP and panic attacks

In a 2004 clinical study, panic disorder patients were made to breathe a 35% atmosphere of carbon dioxide, which typically induces a panic reaction. Those who had been pretreated with 200 mg of 5-HTP had significantly reduced panic symptoms compared with those treated with placebo.¹⁸

5-HTP and coughing

Serotonin acts as a modulator of the cough reflex. With this in mind, researchers in 1986 showed that 5-HTP had the ability to depress the cough reflex in cats.¹⁹ In 1993 a similar result was shown in humans.²⁰ In these experiments the 5-HTP was administered intravenously, but there is no reason to think that oral supplementation would not have similar effects, since the key element is the conversion of 5-HTP to serotonin in the brain -- which occurs whether 5-HTP is taken orally or intravenously.

References

[1]  5-Hydroxytryptophan: a clinically-effective serotonin precursor. Altern Med Rev. 1998 Aug;3(4):271-80 Birdsall TC

[2]  5-Hydroxytryptophan [monograph, PDF, 20KB] www.thorne.com website Thorne Research, Inc.

[3]  5-Hydroxy-L-tryptophan suppresses food intake in food-deprived and stressed rats. Pharmacol Biochem Behav. 2004 Jan;77(1):137-43 Amer A, Breu J, McDermott J, Wurtman RJ, Maher TJ

[4]  5-Hydroxytryptophan (5-HTP) PDRhealth website

[5]  Are tryptophan and 5-hydroxytryptophan effective treatments for depression? A meta-analysis. Aust N Z J Psychiatry. 2002 Aug;36(4):488-91 Shaw K, Turner J, Del Mar C.

[6]  Eating, drinking and activity in rats following 5-hydroxytryptophan (5-htp) administration Psychopharmacologia. 1964 Jun 8;17:417-23 Joyce D, Mrosovsky N

[7]  Eating behavior and adherence to dietary prescriptions in obese adult subjects treated with 5-hydroxytryptophan. Am J Clin Nutr. 1992 Nov;56(5):863-7 Cangiano C, Ceci F, Cascino A, Del Ben M, Laviano A, Muscaritoli M, Antonucci F, Rossi-Fanelli F

[8]  Effects of oral 5-hydroxy-tryptophan on energy intake and macronutrient selection in non-insulin dependent diabetic patients. Int J Obes Relat Metab Disord. 1998 Jul;22(7):648-54 Cangiano C, Laviano A, Del Ben M, Preziosa I, Angelico F, Cascino A, Rossi-Fanelli F

[9]  Pharmacological treatment of obesity. Past, present, and future. Minn Med. 2000 Nov;83(11):21-6 Wangsness M

[10]  Effects of 5-hydroxytryptophan on the sleep of normal human subjects. Electroencephalogr Clin Neurophysiol. 1971 Jun;30(6):505-9 Wyatt RJ, Zarcone V, Engelman K, Dement WC, Snyder F, Sjoerdsma A

[11]  [Effect of 5-hydroxytryptophan, a serotonin precursor, on sleep disorders] [Article in French] Ann Med Psychol (Paris). 1977 May;1(5):792-8 Soulairac A, Lambinet H

[12]  L-5-Hydroxytryptophan treatment of sleep terrors in children. Eur J Pediatr. 2004 Jul;163(7):402-7. Epub 2004 May 14 Bruni O, Ferri R, Miano S, Verrillo E

[13]  From Wikipedia, the free encyclopedia Night terror

[14]  Fibromyalgia and the serotonin pathway. Altern Med Rev. 1998 Oct;3(5):367-75 Juhl JH

[15]  Double-blind study of 5-hydroxytryptophan versus placebo in the treatment of primary fibromyalgia syndrome. J Int Med Res. 1990 May-Jun;18(3):201-9 Caruso I, Sarzi Puttini P, Cazzola M, Azzolini V

[16]  Primary fibromyalgia syndrome and 5-hydroxy-L-tryptophan: a 90-day open study. J Int Med Res. 1992 Apr;20(2):182-9 Puttini PS, Caruso I

[17]  The ingestion of serotonin precursors (L-5-hydroxytryptophan and L-tryptophan) improves migraine headache. Headache. 1973 Apr;13(1):19-22 Sicuteri F

[18]  Acute L-5-hydroxytryptophan administration inhibits carbon dioxide-induced panic in panic disorder patients. Psychiatry Res. 2002 Dec 30;113(3):237-43 Schruers K, van Diest R, Overbeek T, Griez E

[19]  Involvement of central serotonergic mechanisms in the cough reflex. Jpn J Pharmacol. 1986 Dec;42(4):531-8 Kamei J, Hosokawa T, Yanaura S, Hukuhara T

[20]  Effects of 5-hydroxytryptamine and 5-hydroxytryptophan infusion on the human cough reflex. J Appl Physiol. 1993 Jan;74(1):396-401 Stone RA, Worsdell YM, Fuller RW, Barnes PJ

[21]  5-HTP and the B6 controversy delano.com website

Acetyl-L-Carnitine

About Acetyl-L-Carnitine

Acetyl-L-carnitine (ALC) is a biochemical substance made by all organisms except bacteria. Every cell of every plant, animal, yeast, mold, mushroom, and protozoan makes acetyl-L-carnitine molecules and uses them in the extraction of energy from fats. In the body, ALC and L-carnitine are interconvertible.

ALC’s essential role in fat metabolism

Cells are constantly breaking down fat molecules and making new ones. This is how cells

• maintain and repair their internal and external membranes;
• adjust the structure of these membranes in response to changing conditions;
• take advantage of the energy contained in dietary fats.

A fat molecule typically consists of three fatty acids bonded to a glycerol bridge. The process of breaking down fats starts with enzymes that pull the fatty acids off of their glycerol bridges. The free fatty acids are then sent to subcellular organelles called ‘mitochondria’ for further processing.

Mitochondria, however, are bounded by a protective barrier — a double membrane that prevents inappropriate molecules from entering and disrupting the specialized processes that take place inside. Even appropriate molecules may require assistance in passing through this barrier. In particular, many of our dietary fatty acids (the longer-chain ones) are unable to enter a mitochondrion in their free form.

To enable long-chain fatty acids to pass through this barrier, cells ‘tag’ them with a carrier substance called ‘L-carnitine’ — an enzyme attaches a molecule of L-carnitine to each fatty acid. A transporter protein in the inner membrane will now recognize the carnitine-fatty-acid construct and allow it to pass through the membrane into the interior of the mitochondrion.

Once a fatty acid molecule is inside the mitochondrion, its L-carnitine tag is stripped off and the fatty acid is taken up by a processing complex that breaks it into small pieces, exposes the pieces to oxygen atoms, and siphons off the energy released during the resulting chemical reactions, storing it for future use.

What happens to the L-carnitine tags? Some of them are directly transported back out through the mitochondrial membranes into the cell-at-large; these are now ready to transport more fatty acid molecules into the mitochondria. Others of the L-carnitine molecules are converted to acetyl-L-carnitine which is efficiently ferried out of the mitochondria by membrane proteins. Thus, acetic acid molecules use L-carnitine to ‘hitch a ride’ out of the mitochondria so that they can be used in the many ‘acetylation’ processes that take place in cells. Once outside the mitochondria, acetyl-L-carnitine can be deacetylated back to L-carnitine for reuse as a fatty acid transporter.

ALC as a treatment for aging: the theory behind it³⁸

‘Aging’ is a catch-all term that covers many different medical ailments — weakening bones, muscles, and skin; stiffening blood vessels and connective tissue; failing memory, cognition, and sensory organs; loss of cancer suppression; etc. Thousands of medical names have been given to different variations of these ailments — names such as ‘osteoporosis, arthritis, Alzheimer’s, atherosclerosis, pancreatic cancer, macular degeneration, etc. But these age-related ailments share some fundamental causes, such as:

• structural damage by free radicals inside and outside of cells
• protein damage from cross-linking sugars
• growing numbers of incorrectly regulated genes
• skewed proportions of molecules in biological membranes
• biochemical feedback loops that stray from stable patterns.

These (and several other fundamental causes of aging) take place throughout the body, and they affect all the structures inside and outside the cells. Among the structures they affect are the mitochondria — the subcellular organelles that extract energy from fats and carbohydrates. As mitochondria extract energy from these substances, they store the energy in the form of ATP molecules, which are distributed to all parts of all cells in the body.

As cells age, their mitochondria age. The mitochondrial membranes develop skewed proportions of the various molecules they are made of — particularly the lipid molecules which are made from fatty acids. This disrupts the functions of complex nanomachinery which resides in the membranes. Some of these nanomachines transport molecules into and out of the mitochondria; others perform the actual extraction of energy from broken-down fats and carbohydrates, and channel this energy into the production of molecules of ATP.

Thus, a skewed membrane composition causes disrupted nanomachine function, which leads to a defective transport of raw materials and to a decline in ATP production. As the transport system fails and the wrong kinds of molecules are allowed into the mitochondria, the composition of the membranes becomes even more skewed. The energy-extracting nanomachines are forced into non-optimal positions in the membranes and they become less efficient; an increasing percentage of the energy they produce is wasted instead of being stored; and the mitochondria, and the cells they belong to, become starved for energy. The wasted energy is simply dissipated as heat instead of being used for maintaining biological structures and for enabling damaged cells to be replaced.

The current view is that ALC supplementation increases the amount of L-carnitine available for tagging fatty acids in cells. This, in turn, alters the distribution of fatty acids transported into mitochondria. A better fatty acid mix restores the proper proportions of lipid molecules in the mitochondrial membranes. With an improved membrane environment, the nanomachines embedded in the membranes perform better. As a result, the efficiency of energy production in mitochondria is enhanced, enabling more of the energy extracted from food to be stored as ATP instead of being wasted as heat. The subject is too complex to describe here in more detail than this, but the ‘bottom line’ is that ALC rejuvenates mitochondria, and the boost in useful energy that results from this enables cells to behave more youthfully, too.

Potential uses of ALC

Since ALC plays a central role in the production of energy in cells of all kinds, an increase in ALC availability would be expected to ameliorate many different kinds of ailments that involve cellular energy deficiency or impaired fat metabolism. Athletic individuals could reasonably expect that ALC consumption would lead to accelerated fat metabolism and increased endurance during exercise.

But ALC also has effects that seem to be independent of its involvement in energy production. For example, ALC enhances the production of the neurotransmitter acetylcholine, it stimulates the synthesis of protein, and it affects the fluidity of biological membranes. The mechanisms are poorly understood, but we can nevertheless exploit them to alter the performance of our bodies and minds.

Medical conditions which have responded well to ALC supplements include:

• Alzheimer’s, Parkinson’s, and other neurodegenerative diseases^2,3
• Hepatic neuropathy and encephalopathy^4,5
• macular degeneration⁶
• HIV-related lipodystrophy⁷
• increased fat metabolism and endurance during exercise⁸
• diabetes and diabetic neuropathy^1,9,10
• Peripheral neuropathy due to HIV or cancer chemotherapy^1,11
• high blood pressure⁴¹
• recovery from heart attacks⁴²
• recovery from strokes¹²
• age-related memory decline^13,14
• low libido and erectile dysfunction¹⁵
• MS-related fatigue¹⁶
• noise-induced hearing loss^17,18
• Peyronie’s disease¹⁹
• Rett syndrome cardiac failure²⁰
• Nerve injury²¹
• Peripheral neuropathy^1,21
• fibromyalgia²²
• eye-lens stiffening²³
• depression²⁴

Several of these ALC applications have been receiving much attention recently. Let’s look briefly at these.

Alzheimer’s and Parkinson’s

The first clinical study of ALC for treating Alzheimer’s Disease was reported in 1983.²⁵ Wouldn’t you think that by now, a quarter of a century later, the medical world would have settled the question of whether or not this substance should be a standard weapon against this disease? Well, it hasn’t, for reasons that are controversial. Cynics claim that the medical profession downplays all dietary supplements because physicians are being bribed by the makers of prescription drugs. Others claim that mainstream medicine shies away from supplements because they give inconsistent results in human clinical trials — and that these trials of supplements are conducted sloppily, on low budgets, in contrast to prescription drugs, which are tested in high-budget trials.

Be that as it may, many studies of ALC in cell culture, lab animals, and in humans have demonstrated unequivocal anti-Alzheimer’s effects. As summarized in one medical review, “improvements were noted in spatial learning tasks, timed tasks of attention, discrimination-learning tasks, and tasks of personal recognition.”²

Several mechanisms have been suggested through which ALC produces its anti-Alzheimer’s effects. These include anti-oxidant action,²⁶ prevention of apoptosis (cell-death by caused by signalling molecules)²⁶, and prevention of toxicity due to amyloid proteins.²⁷

ALC has received attention from Parkinson’s researchers, too.^28,29 The beneficial action of ALC in Parkinson’s Disease has been shown both in animal models³⁰ and in humans.³ The mechanisms suggested by researchers to explain the anti-Parkson’s effects are vague and involve preventing oxidative damage.²⁸

Brain rejuvenation and nerve repair

ALC enhances the effects of the Nerve Growth Factor — a substance made in the nervous system that stimulates nerve growth. Tissue culture and lab animal experiments show that ALC causes heightened production of the receptor with which nerve cells detect and respond to Nerve Growth Factor. This results in faster repair of damaged nerve cells³¹ and the replacement of brain neurons that have been lost through trauma or aging.³²

Blood pressure and heart protection

Two potential cardiovascular benefits of ALC supplementation were recently shown in clinical studies. First, a significant lowering of blood pressure was seen in patients with coronary artery disease who were given combination of ALC with alpha-lipoic acid for 8 weeks.⁴¹ And second, it was found that heart attacks will cause less damage to the heart if the subjects (lab animals, in these studies) have been treated with ALC a few hours prior to the attacks.⁴²

Bioavailability

It is often stated by promoters of acetyl-L-carnitine that, for use as a supplement, this form of carnitine is superior to L-carnitine itself because it has a higher bioavailability. However, the absolute oral bioavailability of acetyl-L-carnitine has not been determined in humans. It may well be higher than that of L-carnitine (which varies dramatically and inversely with dosage³³). Regardless of what the percentage bioavailability of ALC turns out to be, it does what we want it to do: it raises blood concentrations of ALC, making more of it available to cells throughout the body. In fact, 2 g/day of an oral ALC supplement will increase blood levels to 143% of the pre-dose value.³⁴

Furthermore, ALC readily crosses the blood-brain-barrier.^35,36 Its measurable effects on energy production and on neurotransmitter production in nerve cells have inspired numerous studies of its ability to reverse the mental symptoms of aging and neurodegenerative diseases.³⁷

Dosages and co-supplements

Oral dosages of 1-3 g/day have been used in clinical trials for the medical conditions for which ALC has been studied. In Alzheimer’s studies, for example, a typical dosage would be 500 mg taken three times per day.³⁶ Much higher doses have been studied informally as an anti-aging treatment, with no apparent ill effects.³⁹

Since acetyl-L-carnitine enhances mitochondrial energy production, and since destructive free radicals are always a by-product of this process, it is important to scavenge these free radicals before they can damage the mitochondria and other cellular structures. The standard way to accomplish this scavenging is to use a second supplement — the antioxidant alpha-lipoic acid.⁴⁰ A reasonable dosage would be 100 mg of alpha-lipoic acid three times per day.

Anyone who is considering the use of ALC for treating or preventing Alzheimer’s, Parkinson’s, or other neurodegenerative disease, should also consider the simultaneous use of a curcumin-containing product like LifeLink’s Primeric™. The mechanism of action of curcumin is unrelated to that of ALC, which means that the combination may benefit from synergism.

References

[1]  Peripheral neuropathy: pathogenic mechanisms and alternative therapies. Altern Med Rev. 2006 Dec; 11(4):294-329 Head KA

[2]  Acetyl-L-carnitine. Altern Med Rev. 1999 Dec; 4(6):438-41

[3]  Clinical pharmacodynamics of acetyl-L-carnitine in patients with Parkinson's disease. Int J Clin Pharmacol Res. 1990; 10(1-2):139-43 Puca FM, Genco S, Specchio LM, Brancasi B, D'Ursi R, Prudenzano A, Miccoli A, Scarcia R, Martino R, Savarese M

[4]  Effects of L-acetylcarnitine on cirrhotic patients with hepatic coma: randomized double-blind, placebo-controlled trial. Dig Dis Sci. 2006 Dec; 51(12):2242-7 Malaguarnera M, Pistone G, Astuto M, Vecchio I, Raffaele R, Lo Giudice E, Rampello L

[5]  Effects of a single, short intravenous dose of acetyl-L-carnitine on pattern-reversal visual-evoked potentials in cirrhotic patients with hepatic encephalopathy. Clin Exp Pharmacol Physiol. 2006 Nov; 33(1-2):76-80 Siciliano M, Annicchiarico BE, Lucchese F, Bombardieri G

[6]  Improvement of visual functions and fundus alterations in early age-related macular degeneration treated with a combination of acetyl-L-carnitine, n-3 fatty acids, and coenzyme Q10. Ophthalmologica. 2005 May-Jun; 219(3):154-66 Feher J, Kovacs B, Kovacs I, Schveoller M, Papale A, Balacco Gabrieli C

[7]  Acetyl-L-carnitine for the treatment of HIV lipoatrophy. Ann N Y Acad Sci. 2004 Nov; 1033:139-46 Day L, Shikuma C, Gerschenson M

[8]  New insights concerning the role of carnitine in the regulation of fuel metabolism in skeletal muscle. J Physiol. 2007 Jun 1; 581(Pt 2):431-44 Stephens FB, Constantin-Teodosiu D, Greenhaff PL

[9]  Acetyl-L-carnitine infusion increases glucose disposal in type 2 diabetic patients. Metabolism. 2000 Jun; 49(6):704-8 Giancaterini A, De Gaetano A, Mingrone G, Gniuli D, Liverani E, Capristo E, Greco AV

[10]  Acetyl-L-carnitine (levacecarnine) in the treatment of diabetic neuropathy. A long-term, randomised, double-blind, placebo-controlled study. Drugs R D. 2002; 3(4):223-31 De Grandis D, Minardi C

[11]  Long-term effect of acetyl-L-carnitine for antiretroviral toxic neuropathy. HIV Clin Trials. 2005 Nov-Dec; 6(6):344-50 Herzmann C, Johnson MA, Youle M

[12]  Effect of acute administration of L-acetyl carnitine on cerebral blood flow in patients with chronic cerebral infarct. Pharmacol Res. 1991 Apr; 23(3):241-6 Postiglione A, Soricelli A, Cicerano U, Mansi L, De Chiara S, Gallotta G, Schettini G, Salvatore M

[13]  Acetyl-L-carnitine and α-lipoic acid supplementation of aged beagle dogs improves learning in two landmark discrimination tests. FASEB J. 2007 Jul 10; Milgram NW, Araujo JA, Hagen TM, Treadwell BV, Ames BN

[14]  A review of nutrients and botanicals in the integrative management of cognitive dysfunction. Altern Med Rev. 1999 Jun; 4(3):144-61 Kidd PM

[15]  Carnitine versus androgen administration in the treatment of sexual dysfunction, depressed mood, and fatigue associated with male aging. Urology. 2004 Apr; 63(4):641-6 Cavallini G, Caracciolo S, Vitali G, Modenini F, Biagiotti G

[16]  Comparison of the effects of acetyl L-carnitine and amantadine for the treatment of fatigue in multiple sclerosis: results of a pilot, randomised, double-blind, crossover trial. J Neurol Sci. 2004 Mar 15; 218(1-2):103-8 Tomassini V, Pozzilli C, Onesti E, Pasqualetti P, Marinelli F, Pisani A, Fieschi C

[17]  Prevention of impulse noise-induced hearing loss with antioxidants. Acta Otolaryngol. 2005 Mar; 125(3):235-43 Kopke R, Bielefeld E, Liu J, Zheng J, Jackson R, Henderson D, Coleman JK

[18]  Pharmacological rescue of noise induced hearing loss using N-acetylcysteine and acetyl-L-carnitine. Hear Res. 2007 Apr; 226(1-2):104-13 Coleman JK, Kopke RD, Liu J, Ge X, Harper EA, Jones GE, Cater TL, Jackson RL

[19]  Towards an evidence-based understanding of Peyronie's disease. Int J STD AIDS. 2005 Mar; 16(3):187-94; quiz 94-5 Cavallini G

[20]  Effects of acetyl-L-carnitine on cardiac dysautonomia in Rett syndrome: prevention of sudden death? Pediatr Cardiol. 2006 Mar; 26(5):574-7 Guideri F, Acampa M, Hayek Y, Zappella M

[21]  Delayed acetyl-L-carnitine administration and its effect on sensory neuronal rescue after peripheral nerve injury. J Plast Reconstr Aesthet Surg. 2007; 60(2):114-8 Wilson AD, Hart A, Brännström T, Wiberg M, Terenghi G

[22]  Double-blind, multicenter trial comparing acetyl l-carnitine with placebo in the treatment of fibromyalgia patients. Clin Exp Rheumatol. 25(2):182-8 Rossini M, Di Munno O, Valentini G, Bianchi G, Biasi G, Cacace E, Malesci D, La Montagna G, Viapiana O, Adami S

[23]  Acetyl- L -carnitine decreases glycation of lens proteins: in vitro studies. Exp Eye Res. 1999 Jul; 69(1):109-15 Swamy-Mruthinti S, Carter AL

[24]  A double-blind, randomised, controlled clinical trial of acetyl-L-carnitine vs. amisulpride in the treatment of dysthymia. Eur Neuropsychopharmacol. 2006 May; 16(4):281-7 Zanardi R, Smeraldi E

[25]  [The use of 1-acetylcarnitine in (presenile and senile) Alzheimer's disease. Preliminary results] Clin Ter. 1983 Apr 30; 105(2):135-45 Acierno G

[26]  Acetyl-L-carnitine-induced up-regulation of heat shock proteins protects cortical neurons against amyloid-beta peptide 1-42-mediated oxidative stress and neurotoxicity: implications for Alzheimer's disease. J Neurosci Res. 2006 Aug 1; 84(2):398-408 Abdul HM, Calabrese V, Calvani M, Butterfield DA

[27]  Folate, vitamin E, and acetyl-L-carnitine provide synergistic protection against oxidative stress resulting from exposure of human neuroblastoma cells to amyloid-beta. Brain Res. 2005 Nov 9; 1061(2):114-7 Dhitavat S, Ortiz D, Rogers E, Rivera E, Shea TB

[28]  Bioenergetic approaches for neuroprotection in Parkinson's disease. Ann Neurol. 2003; 53 Suppl 3:S39-47; discussion S47-8 Beal MF

[29]  Neurodegeneration from mitochondrial insufficiency: nutrients, stem cells, growth factors, and prospects for brain rebuilding using integrative management. Altern Med Rev. 2005 Dec; 10(4):268-93 Kidd PM

[30]  Acetyl-levo-carnitine protects against MPTP-induced parkinsonism in primates. J Neural Transm Park Dis Dement Sect. 1991; 3(1):63-72 Bodis-Wollner I, Chung E, Ghilardi MF, Glover A, Onofrj M, Pasik P, Samson Y

[31]  Levocarnitine acetyl stimulates peripheral nerve regeneration and neuromuscular junction remodelling following sciatic nerve injury. Int J Clin Pharmacol Res. 1992; 12(5-6):269-79 De Angelis C, Scarfò C, Falcinelli M, Reda E, Ramacci MT, Angelucci L

[32]  Acetyl-L-carnitine treatment increases nerve growth factor levels and choline acetyltransferase activity in the central nervous system of aged rats. Exp Gerontol. 1994 Jan-Feb; 29(1):55-66 Taglialatela G, Navarra D, Cruciani R, Ramacci MT, Alemà GS, Angelucci L

[33]  Multiple-dose pharmacokinetics and bioequivalence of L-carnitine 330-mg tablet versus 1-g chewable tablet versus enteral solution in healthy adult male volunteers. J Pharm Sci. 1995 May; 84(5):627-33 Sahajwalla CG, Helton ED, Purich ED, Hoppel CL, Cabana BE

[34]  Kinetics, pharmacokinetics, and regulation of L-carnitine and acetyl-L-carnitine metabolism. Ann N Y Acad Sci. 2004 Nov; 1033:30-41 Rebouche CJ

[35]  Acetyl-L-carnitine in Alzheimer disease: a short-term study on CSF neurotransmitters and neuropeptides. Alzheimer Dis Assoc Disord. 1995; 9(3):128-31 Bruno G, Scaccianoce S, Bonamini M, Patacchioli FR, Cesarino F, Grassini P, Sorrentino E, Angelucci L, Lenzi GL

[36]  Pharmacokinetics of IV and oral acetyl-L-carnitine in a multiple dose regimen in patients with senile dementia of Alzheimer type. Eur J Clin Pharmacol. 1992; 42(1):89-93 Parnetti L, Gaiti A, Mecocci P, Cadini D, Senin U

[37]  Role of carnitine esters in brain neuropathology. Mol Aspects Med. 2004 Oct-Dec; 25(5-6):533-49 Virmani A, Binienda Z

[38]  Oxidative damage and mitochondrial decay in aging. Proc Natl Acad Sci U S A. 1994 Nov 8; 91(23):10771-8 Shigenaga MK, Hagen TM, Ames BN

[39]  ALC+ALA: One month of “rejuvenation” Delano Report website; 2003 Nov Mills R

[40]  Alpha-Lipoic Acid and Acetyl-L-Carnitine: New evidence for rejuvenation potential Delano Report website; 2002 Feb

[41]  Effect of combined treatment with alpha-Lipoic acid and acetyl-L-carnitine on vascular function and blood pressure in patients with coronary artery disease. J Clin Hypertens (Greenwich). 2007 Apr; 9(4):249-55 McMackin CJ, Widlansky ME, Hamburg NM, Huang AL, Weller S, Holbrook M, Gokce N, Hagen TM, Keaney JF, Vita JA

[42]  Reversal of mitochondrial defects before ischemia protects the aged heart. FASEB J. 2006 Jul; 20(9):1543-5 Lesnefsky EJ, He D, Moghaddas S, Hoppel CL

R-Lipoic Acid ( The refined form of Alpha Lipoic Acid )

About R-Lipoic Acid