Biomedical Tidbits

ALC Recharges Low-Energy Brains Higher levels of acetyl L-carnitine (ALC) can help to alleviate an energy crisis in the brain such as that associated with lower levels of glucose.

  • Kuratsune H, Watanabe Y, Yamaguti K, et al. High uptake of [2-11C]acetyl-L-carnitine into the brain: a PET study. Biochem Biophys Res Commun. 1997;231:488-93

5-HTP Suppresses Appetite 5-hydroxytryptophan (5-HTP) behaves as an appetite suppressant even if taken at low doses (50-100 mg). To be most effective, 5 HTP should be taken with a low-glycemic carbohydrate, such as fructose, about 45 minutes before meals. 5-HTP is readily converted into serotonin in the brain, which in turn causes the release of CCK, the satiety hormone.

  • Ju CY, Tsai CT. Serotonergic mechanisms involved in the suppression of feeding by 5-HTP in rats. Chin J Physiol. 1995;38:235-240.
  • Martinelli I, Mainini E, Mazzi C. Effect of 5-hydroxytryptophan on the secretion of PRL, GH, TSH and cortisol in obesity. Minerva Endocrinol. 1992;17:121-126.

5-HTP Helps Relieve PMS When converted into serotonin, 5-HTP helps reduce sensitivity to pain. Because pain sensitivity has been found to be one of the principal contributing factors to PMS, 5-HTP can help alleviate irritability, agitation, and other characteristics of PMS.

  • Sayegh R, Schiff I, Wurtman J, Spiers P, McDermott J, Wurtman R. The effect of a carbohydrate-rich beverage on mood, appetite, and cognitive function in women with premenstrual syndrome.Obstet Gynecol. 1995;86:520-528.

5-HTP Enhances SSRI Effects Depressed patients taking an SSRI (selective serotonin reuptake inhibitor, e.g., Zoloft, Paxil, or Prozac) who had low levels of tryptophan in their diet were found to quickly lapse back into depression. Supplementation with tryptophan restored the antidepressant effects of the SSRI. 5-HTP can produce serotonin more efficiently than tryptophan.

  • Delgado PL, Miller HL, Salomon RM, et al. Monoamines and the mechanism of antidepressant action: effects of catecholamine depletion on mood of patients treated with antidepressants.Psychopharmacol Bull. 1993;29:389-396.

Pregnenolone Stabilizes Cortisone Pregnenolone (PREG) can help ease withdrawal from cortisone treatment and possibly prevent adrenal atrophy (Addison's disease) under such circumstances. Because of PREG's stabilizing effect on cortisone levels and the adrenals, it may help relieve the stress elevation associated with diabetes.

  • Peat R. Three youth-associated hormones. 1996;

Lipoic Acid for Liver Health Alpha-lipoic acid (ALA) is a natural antioxidant that has been used to help maintain or restore liver health. In Europe it has been used under emergency conditions to treat overdoses and poisoning from radiation and mushrooms. ALA has proven to be beneficial even for alcoholic hepatitis. When drugs or certain foods are rapidly metabolized by the liver, the results can be high enzyme levels representing threat of free-radical damage. As a high-powered and universal antioxidant, ALA can help normalize these enzymes.

  • Ramakrishnan N, Wolfe WW, Catravas GN. Radioprotection of hematopoietic tissues in mice by lipoic acid. Radiat Res. 1992;130:360-365.

Glucosamine Improves Joint Function Glucosamine, naturally formed in the human body from glucose, is necessary for the synthesis of a group of long-chain modified sugars known as glycosaminoglycans which serve important structural functions in the body, including facilitating effortless joint movement. The lubricant enabling proper joint movement is synovial fluid. A principal component of synovial fluid is hyaluronic acid, a subcomponent of which is acetyl glucosamine (AG). By contributing to the antioxidant ability of hyaluronic acid, AG may also help arrest the oxidative processes associated with arthritis.

  • Sato H, Takahashi T, Ide H, Fukushima T, et al. Antioxidant activity of synovial fluid, hyaluronic acid, and two subcomponents of hyaluronic acid. Synovial fluid scavenging effect is enhanced in rheumatoid arthritis patients. Arthritis Rheum. 1988;31:63-71.

Melatonin and Immune Function Melatonin may play a complex physiological role in neuronal signaling and immune system modulation. It is also possible that melatonin may help allergies. Cutando A, Silvestre FJ. Melatonin: implications at the oral level.

  • Bull Group Int Rech Sci Stomatol Odontol. 1995;38:81-86.

Green Tea Prevents Prostate and Breast Cancer Green tea's cancer prevention ability may involve the action of a chemical known as a catechin, also known as epigallocatechin-3 gallate (EGCG), which inhibits urokinase, an enzyme crucial for cancer growth. EGCG attaches to urokinase and prevents it from invading cells and forming tumors in the prostate and breast.

  • Liao S, Umekita Y, Guo J, Kokontis JM, Hiipakka RA. Growth inhibition and regression of human prostate and breast tumors in athymic mice by tea epigallocatechin gallate. Cancer Lett.1995;96:239-243.

PREG and PROG Help Overcome Fear and Anxiety In the Little Orphan Annie comic strip, Punjab, an Indian swami complete with turban, is chosen by Daddy Warbucks to guard Annie, watch over her, lighten her burdens, and see that no harm comes to her. Recently, scientists at Punjab University in India examined the effects of neurosteroids such as DHEA and Pregnenolone (PREG) on the behavior of mice under anxiety-producing conditions. What they found creates a new understanding of how neurosteroids operate to alleviate anxiety and in-so-doing, lighten your burdens. Call it the "Punjab effect."

Mice were given amounts of PREG equivalent to a proportional human dose of 35 to 140 mg and then introduced to a mirrored chamber (which would normally make them fearful). The researchers then measured the reluctance of the mice to enter the chamber. PREG significantly reduced the fear of entry without affecting spontaneous locomotor activity. The reduction of entrance-anxiety varied with dose; the greater the dose, the more time the mice spent in the fear-chamber and the greater the number of times they entered.

Progesterone (PROG) at proportional human equivalence of 70 to 700 mg produced positive results, similar to PREG. Curiously, though, DHEA at the proportional human equivalence of 70 to 140 mg produced negative results: there were increases in motor activity and anxiogenic responses - just the opposite of PREG - with fewer entries and less time spent in the chamber. DHEA increased the fear of entry in the same anxiety-provoking circumstance.

Although the positive anxiolytic responses for PROG were blocked by a GABAA chloride channel antagonist, a selective benzodiazepine antagonist did not have anxiety-reducing effects. In contrast, the anxiety-reducing effect of PREG was not blocked by GABAA chloride channel antagonist.

Unlike PREG and PROG, drugs such as triazolam (Halcion®), which are capable of eliciting similar responses, did not markedly affect locomotor activity. This finding suggested that the changes in behavior were anxiolytic actions. Although the mechanisms may be different for each steroid, it seems likely that, taken as a whole, neurosteroids are involved in the homeostasis of stress response.

  • Reddy DS, Kulkarni SK. Differential anxiolytic effects of neurosteroids in the mirrored chamber behavior test in mice Brain Res. 1997;752: 61-71.

Scent, Sight and PREG, DHEA and PROG When young adult male rats were exposed to the scent or scent and sight of young cycling female rats, their levels of pregnenolone (PREG), DHEA and progesterone (PROG) increased or varied significantly in specific areas of the brain or retina compared with males exposed to other males.1

When male rats were exposed to the scent and sight of female rats, DHEA levels increased significantly in the olfactory bulb and retina, while PROG decreased significantly in the hypothalamus, amygdala, and parietal cortex, and PREG levels decreased significantly in the olfactory bulb. PREG has been found to have binding sights in the cytosolic fraction of the rat olfactory bulb.2 PREG is synthesized in the retina and probably elsewhere in the eyes.3

Evidence supports the view that neuroactive steroids may play an important role in regulating some aspects of neuroendocrine function within the hypothalamus,4 the seat of emotion, fear, hope, and sensory evaluation. When author Ray Sahelian, M.D. tells us in his new book, Pregnenolone - Nature's Feel-Good Hormone, that he is 100% sure that PREG enhances perception, we must recognize that we cannot yet scientifically prove it. Yet the evidence mounts.

  1. Lanthier A, Patwardhan VV. Effect of heterosexual olfactory and visual stimulation on 5-en-3 beta-hydroxysteroids and progesterone in the male rat brain. J Steroid Biochem. 1987;28:697-701.
  2. Lanthier A, DiBattista JA, Patwardhan VV. Pregnenolone binding sites in the rat olfactory bulb. J Steroid Biochem. 1990;35:487-494.
  3. Guarneri P, Guarneri R, Cascio C, Pavasant P, Piccoli F, Papadopoulos V. Neurosteroidogenesis in rat retinas. J Neurochem. 1994;63: 86-96.
  4. Murray HE.; Gillies GE. Differential effects of neuroactive steroids on somatostatin and dopamine secretion from primary hypothalamic cell cultures. J Neuroendocrin. 1997;9:287-295.

ALC and Energy Depletion When an enzyme known as hepatic ornithine transcarbamylase (OTC) is depleted in a particular strain of Sparse-fur (spf) mice, the result is elevated cerebral ammonia and depleted energy. This disorder is similar to human OTC deficiency, which is characterized by Alzheimer's-type neurodegeneration in which cytochrome C oxidase (COX) is reduced. There is also a progressive decrease in COX activity in the spf mouse.

Short-term treatment with acetyl L-carnitine (ALC) was found to restore these abnormalities. It is thought that ALC works on reducing cerebral ammonia-induced alterations, causing a decrease in COX activity. ALC thus may be able to normalize cerebral energy metabolism.

  • Rao KV, Mawal YR, Qureshi IA. Progressive decrease of cerebral cytochrome C oxidase activity in sparse-fur mice: role of acetyl-L-carnitine in restoring the ammonia-induced cerebral energy depletion. Neurosci Lett. 1997;224:83-86.

Can ALC Restore Spatial Memory in Anoxic Children? Rats starved for oxygen in the birthing process were given acetyl L-carnitine (ALC). Controls not receiving ALC were noticeably hyperactive within weeks after birth and experienced spatial memory deficits. Those chronically treated with ALC (at human proportional equivalents of 3.5 g/day) during the same period that the controls were observed showed improvement in sniffing, rearing and locomotor activity. Also, ALC significantly enhanced their spatial memory performance in mazes, including a water maze. The scientists concluded that the use of ALC would probably be beneficial for the treatment of perinatal asphyctic insults in children.

  • Dell'Anna E, Iuvone L, Calzolari S, Geloso MC. Effect of acetyl-L-carnitine on hyperactivity and spatial memory deficits of rats exposed to neonatal anoxiaNeurosci Lett. 1997;223:201-205.

DHEA for Arthritis Collagen-induced arthritis (CIA) is a model for rheumatoid arthritis. DHEA supplementation prior to induction of CIA delayed onset of the disease and decreased its severity.1 DHEA administered after the onset of arthritis was not found to be beneficial. Other studies have indicated that low levels of DHEA are associated with the development of rheumatoid arthritis.2

  1. Williams PJ, Jones RHV, Rademacher TW. Reduction in the incidence and severity of collagen-induced arthritis in DBA/1 mice, using exogenous dehydroepiandrosterone. Arthrit Rheum.1997;40:907-911.
  2. Nilsson E, de la Torre B, Hedman M, Goobar J, Thorner A. Blood dehydroepiandrosterone sulphate (DHEAS) levels in polymyalgia rheumatica/giant cell arteritis and primary fibromyalgia.Clin Exp Rheumatol. 1994;12:415-417.

Phosphatidylserine May Suppress Demyelinating Disease The effect of phosphatidylserine (PS) on mice with immune-mediated demyelinating disease (IDD) was studied.1 The effect of IDD on the central nervous system appears to be similar to that of human multiple sclerosis (MS), and thus, this system provides an excellent infectious animal model for studying MS. When PS was administered in the effector phase, IDD was significantly suppressed both clinically and histologically. As a measure of the effect of PS on IDD, the number of TNF-a (tumor necrosis factor)-producing spleen cells was reduced. TNF-a contributes to the further development of perivascular cellular infiltration and demyelination in the central nervous system (CNS). PS, a major anionic phospholipid of mammalian cells, is believed to function as a regulator of immune and inflammatory responses, especially reducing TNF-a production and release in mice. As prior work has shown, PS induces histamine release by mast cells, and it is known that histamine inhibits TNF release.2

  1. Yamazaki M, Inoue A, Koh C-S, Sakai T, Ishihara Y. Phosphatidylserine suppresses Theiler's murine encephalomyelitis virus-induced demyelinating disease. J Neuroimmun. 1997;75:113-122.
  2. Secchi EF, Monastra G, Bruni A, Chizzolini C. Adrenalectomy abolishes phosphatidylserine inhibition of lipopolysaccharide-induced tumor necrosis factor release. Eur Cytokine. 1993;4:371-375.

Melatonin Reverses Tolerance to Traditional Hypnotics Drugs of the benzodiazepine class (e.g., Halcion®) have long been the standard hypnotics against which other sleeping agents are judged. For a 43-year-old woman suffering from 11 years of insomnia, however, benzodiazepine treatment has been a nightmare, literally as well as figuratively. Every attempt to stop benzodiazepine treatment resulted in withdrawal symptoms and a renewal of the insomnia.

But when she added 1 mg of melatonin to her nightly regimen, within two days she was able to withdraw from use of the benzodiazepine. Moreover, she experienced an improvement in sleep quality without side effects. Examination of her levels of urinary melatonin metabolites revealed that supplementation with melatonin had restored her abnormal non-circadian rhythmic excretion of melatonin to normal.

  • Dagan Y, Zisapel N, Nof D, Laudon M, Atsmon J. Rapid reversal of tolerance to benzodiazepine hypnotics by treatment with oral melatonin: a case report. Eur Neuropsychopharmacol.1997;7:157-160.

Melatonin Protects the Gastric Mucosa Only a few years ago melatonin, a pineal hormone that is biosynthesized in the brain from tryptophan or 5-HTP, was found to also be present in the gut.1 It was hypothesized at the time that its presence and apparent manufacture there might be responsible for the longevity benefits of caloric deprivation, which was thought to increase its abundance.

Now, a study indicates that melatonin decreases the formation of acute gastric lesions induced by stress and ischemia-reperfusion but not by topical irritants, such as ethanol or acetylsalicylic acid (aspirin).2Melatonin provides these benefits through its ability, in part, to limit free radicals, stimulate mucosal generation of prostaglandins and increase gastric blood flow.

  1. Lee PP, Pang SF. Melatonin and its receptors in the gastrointestinal tract. Biol Signals.1993;2:181-193.
  2. Konturek PC, Konturek SJ, Brzozowski T, et al. Gastroprotective activity of melatonin and its precursor, L-tryptophan, against stress-induced and ischaemia-induced lesions is mediated by scavenge of oxygen radicals. Scand J Gastroenterol. 1997;32:433-438.

Originally published by Will Block at