references:

Bartus RT, Dean RL III, Beer B, Lippa AS. The cholinergic hypothesis of geriatric memory dysfunction, Science. 1982;217:408-414. 2. Larson EB, Kukull WA, Katzman RL. Cognitive impairment: Dementia and Alzheimer's disease. Annu Rev Public Health. 1992;13:431-449. 3. Hofman A, Rocca WA, Brayne C, et al, for the European Prevalence Research Group. The prevalence of dementia in Europe: A collaborative study of 1980-1990 findings. Int d Epidemiol. 1991;20:736-748. 4. Blackwood W, Corsellis JAN, eds. Greenfield's Neuropathology. 3rd ed. London: Arnold; 1976. 5. Geldmacher DS. Cost-effective recognition and diagnosis of dementia. 5emin Neurol. 2002;22:63-70. 6. Perry EK, Tomlinson BE, Blessed G, et al. Correlation of cholinergic abnormalities with senile plaques and mental test scores in senile dementia. BMJ. 1978;2:1457-1459. 7. Perry EK. The cholinergic hypothesis--ten years on. Br Med Bull. 1986;42:63-69. 8. Giacobini E. From molecular structure to Alzheimer therapy. Jpn d Pharmacol. 1997;74:225-241. 9. Giacobini E. Invited review: Cholinesterase inhibitors for Alzheimer's disease therapy: From tacrine to future applications. Neurochem Int. 1998;32:413-419. 10. Brinkman SD, Smith RC, Meyer JS, et al. Lecithin and memory training in suspected Alzheimer's disease. J Gerontol. 1982;37:4-9. 11. Davis E, Emmerling MR, Jaen JC, et al. Therapeutic intervention in dementia. Crit Rev Neurobiol. 1993;7:41-83. 12. Amenta E Parnetti L, Gallai V, Wallin A. Treatment of cognitive dysfunction associated with Alzheimer's disease with cholinergic precursors. Ineffective treatments or inappropiate approaches? Mech Ageing Dev. 2001;122:2025-2040. 13. Sigala S, Imperato A, Rizzonelli P, et al. k-Alpha-glycerylphosphorylcholine antagonizes scopolamine-induced amnesia and enhances hippocampal cholinergic transmission in the rat. Eurd Pharmacol. 1992;211:351-358. 14. Govoni S, Battaini E Lucchi L, et al. Effects of alpha-glycerylphosphorylcholine in counteracting drug-induced amnesia: Through cholinergic and non-cholinergic mechanisms [in Italian]. Basi Raz Ter. 1991;21:75-78. 15. Canonico PL, Nicoletti F, Scapagnini U. Neurochemical and behavioral effects of alpha-glycerylphosphorylcholine [in Italian]. Basi Raz Te~ 1990;20: 53-54. 191 CLINICAL THERAPEUTICS ® 16. Parnetti L, Amenta E Gallai V. Choline alphoscerate in cognitive decline and in acute cerebrovascular disease: An analysis of published clinical data. Mech Ageing Dev. 2001;122:2041-2055. 17. Venn RD. The Sandoz Clinical Assessment-Geriatric (SCAG) scale. A general-purpose psychogeriatric rating scale. Gerontology. 1983;29:185-198. 18. Di Perri R, Coppola G, Ambrosio LA, et al. A multicentre trial to evaluate the efficacy and tolerability of alpha-glycerylphosphorylcholine versus cytosine diphosphocholine in patients with vascular dementia. J Int Med Res. 1991;19:330-341. 19. Frattola L, Piolti R, Bassi S, et al. Multicenter clinical comparison of the effects of choline alphoscerate and cytidine diphosphocholine in the treatment of multi-infarct dementia. Curt Ther Res Clin Exp. 1991;49:683-693. 20. Muratorio A, Bonuccelli U, Nuti A, et al. A neurotropic approach to the treatment of multi-infarct dementia using L-c~-glycerylphosphorylcholine. Curt Ther Res Clin Exp. 1992;52:741-75l. 21. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Washington, DC: APA; 1994. 22. McKhann G, Drachman D, Folstein M, et al. Clinical diagnosis of Alzheimer's disease: Report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology. 1984;34:939-944. 23. Folstein ME Folstein SE. "Mini-mental state": A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975; 12:189-198. 24. Loeb C, Gandolfo C. Diagnostic evaluation of degenerative and vascular dementia. Stroke. 1983;14:399-401. 25. Hamilton M. A rating scale for depression.J Neurol Neurosurg Psychiatry. 1960;23:56-62. 26. Hamilton M. Development of a rating scale for primary depressive illness. BrJ Soc Clin Psych& 1967;6:278-296. 27. Rosen WG, Mohs RC, Davis KL. A new rating scale for Alzheimer's disease. AmJ Psychiatry. 1984;141:1356-1364. 28. Reisberg B, Ferris SH, De Leon MJ, et al. The Global Deterioration Scale for assessment of primary degenerative dementia. Am J Psychiatry. 1982;139:1136-1139. 29. National Institute of Mental Health. Clinical global impressions. In: Guy W, ed. ECDEU Assessment for Psychopharmacology. Revised edition. Rockville, Md: National Institute of Mental Health; 1976:217-222. 30. Burns A, Russell E, Page S. New drugs for Alzheimer's disease. Br J Psychiatry. 1999;174:476-479. 31. Kumar V, Anand R, Messina J, et al. An efficacy and safety analysis of Exelon in Alzheimer's disease patients with concurrent vascular risk factors. Eur J Neurol. 2000;7:159-169. 32. Knapp MJ, Knopman DS, Solomon PR, et al, for the Tacrine Study Group. A 30-week randomized controlled trial of high-dose tacrine in patients with Alzheimer's disease. JAMA. 1994;271:985-991. 192 M. Moreno 33. Lindstrom MJ, Bates DM. Newton-Rapshon algorithms for linear-mixed effects models for repeated measure data. J Am Stat Assoc. 1998;83:1014-1022. 34. Thai LJ, Carta A, Clarke WR, et al. A 1-year multicenter placebo-controlled study of acetyl-L-carnitine in patients with Alzheimer's disease. Neurology 1996;47:705-711. 35. Rogers SL, Friedhoff LT, for the Donepezil Study Group. The efficacy and safety of donepezil in patients with Alzheimer's disease: Results of a US multicentre, randomized, double-blind, placebo-controlled trial. Dementia. 1996;7:293-303. 36. Rogers SL, Doody RS, Mohs RC, Friedhoff LT, for the Donepezil Study Group. Donepezil improves cognition and global function in Alzheimer disease: A 15-week, double-blind, placebo-controlled study. Arch Intern Med. 1998; 158:1021-1031. 37. Corey-Bloom J, Anand R, Veach J, for the ENA 713 B352 Study Group. A randomized trial evaluating the efficacy and the safety of ENA 713 (rivastigmine tartrate), a new acetylcholinesterase inhibitor, in patients with mild to moderately severe Alzheimer's disease. Int J Geriatr Psychopharmacol. 1998;1:55-65. 38. Rosler M, Anand R, Cicin-Sain A, et al. Efficacy and safety of rivastigmine in patients with Alzheimer's disease: International randomised controlled trial. BMJ. 1999;318: 633-638. 39. Amenta E Bronzetti E, Del Valle M, Vega JA. Effects of alpha-glycerylphosphorylcholine in neuroanatomy of aging brain in experimental animals [in Italian]. Basi Raz Te~: 1990;20:31-38. Address correspondence to: Scientific Department, Italfarmaco SpA, via dei Lavoratori 54, 20092 Cinisello Balsamo, Milan, Italy.

(https://vitanetonline.com:443/forums/Index.cfm?CFApp=1&Message_ID=98)

Date: May 12, 2005 10:00 AM
Author: Darrell Miller (dm@vitanetonline.com)
Subject: Under-Reported (and Underappreciated) Cholesterol control.

Under-Reported (and Underappreciated) Solutions for Cholesterol and Triglyceride Control

Fat and human existence are inseparable. Setting aside the fear and loathing over fat in the body that pervades our culture, we understand that fat is our friend. We cannot live without fat.

The human body contains many different kinds of fats and fat-like molecules. Collectively known as "lipids" these fatty substances include fatty acids, lipoproteins, phospholipids, glycolipids, triglycerides, steroid hormones and the infamous, dreaded cholesterol.

Lipids (fats) are found everywhere in the body, performing a variety of vital functions. The brain is a fat-rich organ. Brain neurons and all other nerve cells are protected by a myelin sheath, made largely out of fatty material. Cell membranes consist almost entirely of phospholipids (lipids that contain phosphorus) arranged in a sandwich-like double layer embedded with proteins. Sex hormones are lipids, belonging to the group of complex lipid molecules known as "steroids." Vitamin D is a lipid.

The body stores and transports fatty acids in the form of triglycerides. A triglyceride contains three fatty acid molecules, which have a chain-like structure, linked to glycerol. (There are also mono- and di-glycerides, which have one and two fatty acid chains, respectively, attached to glycerol.)

Like many other things necessary to life, fat is a two-edged sword. Fat insulates us from the cold, cushions and protects our vital organs and serves as a storehouse for energy. Yet, when present in excess to the point of obesity, fat threatens health, happiness, self-esteem, social standing and longevity. The same is true of other lipids, most notably triglycerides and cholesterol. Transported throughout the body in the bloodstream, these essential lipids become a health liability when the blood contains too much of them.

Keeping fat in it its proper place, not eliminating or drastically reducing it, is the goal we should seek. In the blood, lipids must be maintained at healthy levels and ratios. When they are, an important foundation of good health is established.

How do we keep the blood lipids we need——triglycerides and the various forms of cholesterol——balanced at healthy levels? Diet and exercise are indispensable, these basics must come first. Along with the recommended dietary practices, a number of nutritional approaches offer help for maintaining healthy blood lipids. We will now give several of these a closer look.

Gugulipid

In 1990, an herb used for centuries in the Far East was introduced to U.S. consumers. This herb, called "gum guggul," is proving to be one of the most effective natural cholesterol-lowering agents ever discovered. It also brings triglycerides down and raises HDL, the "good" cholesterol. The changes are substantial; gum guggul single-handedly normalizes the entire blood lipid profile, even in people with high starting levels of cholesterol and triglycerides.

Gum guggul, also called simply "guggul," is a gummy resin tapped from the Commiphora tree. A cousin of myrrh gum, guggul has been used by Ayurvedic herbalists of India for at least 3,000 years; texts dating from around 1,000 B.C. mention the herb. Guggul was traditionally given for rheumatism and poor health caused by excess consumption of fatty foods. One ancient Sanskrit text describes in detail what happens in the body when blood fats are out of balance, due to sedentary lifestyle and overeating. The name of this condition has been translated as "coating and obstruction of channels."

Intrigued by the obvious similarity between "coating and obstruction of channels" and arteries clogged by fatty plaque, Indian researchers initiated a series of experimental and clinical studies in the 1960's to see if gum guggul would lower excess blood lipids.1 Both human and animal studies consistently showed cholesterol and triglyceride reductions.

Detailed pharmacological studies showed that guggul's lipid-lowering effects are produced by compounds in the resin called "guggulsterones."2 An Indian pharmaceutical firm then patented a standardized extract of gum guggul under the trade name "Gugulipid." The product contains a uniform 2.5 percent guggulsterones, which is higher than guggul resin in its natural state.

Because Gugulipid guarantees the necessary intake of guggulsterones needed for blood fat reduction, it has become the product used in clinical research. Phase I efficacy safety trials and Phase II efficacy trials have yielded more positive data.3,4,5 Most of the studies on gum guggul have used relatively small numbers of subjects; this tends to make mainstream medical scientists reluctant about natural remedies. A large, well-publicized double-blind Gugulipid trial on 400 to 500 people would go a long way toward giving this herb the credibility it deserves.

Pantethine

Another effective natural solution for blood fat control that should be better known is a relative of pantothenic acid (vitamin B5). Pantethine is the active form of pantothenic acid in the body. Pantethine forms CoA, an essential co-enzyme for utilization of fat. CoA transports "active acetate," an important byproduct of fat metabolism that provides fuel for generating cellular energy. By promoting the burning of fats for energy, pantethine helps keep triglyceride levels down.6 Pantethine also helps regulate cholesterol production, by facilitating the conversion of fat into other lipid-based molecules needed in the body.6

Japanese researchers began studying the effect of pantethine on blood fats nearly twenty years ago. They reported their promising results at the Seventh International Symposium on Drugs Affecting Lipid Metabolism, held in Milan, Italy in 1980.7 Few in the medical or scientific communities took notice. Italian researchers followed up with several small clinical trials that confirmed the preliminary reports.6,8,9 An excellent cholesterol and triglyceride lowering agent that is safe and free of side-effects, pantethine remains, for the most part, ignored by mainstream science, although its usage is growing in alternative medicine circles. Pantethine it will no doubt prove to be one of the most important supplements for maintaining healthy blood fat levels.

Niacin

When taken in high enough doses, niacin (vitamin B3) substantially lowers cholesterol. This has been known to medical science for many years.10 studies on niacin as a cholesterol-lowering agent go back to the 1950's. There was a fair amount of initial enthusiasm for niacin because it improves, unlike most lipid-lowering drugs, all parameters of the blood lipid profile. Niacin reduces total cholesterol, LDL cholesterol and triglycerides. It also raises HDL cholesterol quite well. Interest in niacin has faded, in part because the necessary dose, 1200 milligrams a day or more, can cause flushing and gastrointestinal disturbances. Very high doses may be harmful to the liver if taken for too long.

There is a solution to the side-effect problem with niacin which, again, has failed to gain widespread attention. Inositol hexanicotinate is a flush-free form of niacin composed of six niacin molecules bonded to one molecule of inositol, another B-complex nutrient. Absorbed as an intact structure, inositol hexanicotinate is metabolized slowly, releasing free niacin into the bloodstream over a period of hours following ingestion.11 Inositol hexanicotinate has all the benefits of niacin for controlling blood fats. The flushing effect of ordinary niacin, which metabolizes much more rapidly, does not occur. Taking as much as four grams per day has not been reported to raise liver enzymes or cause other side-effects, but prudence dictates that people with liver problems should avoid very high doses of inositol hexanicotinate, or any form of niacin.12

Tocotrienols

We often think of vitamin E as synonymous with d-alpha tocopherol. Vitamin E is actually a whole family of compounds that includes various tocopherols and a group of lesser known but highly beneficial substances called "tocotrienols." All have vitamin E activity. Tocotrienols are similar in chemical structure to tocopherols, but they have important differences which give them unique and highly beneficial properties for human health.

Vitamin E is one of the most recognized antioxidants, nutrients that deactivate potentially toxic byproducts of oxygen metabolism known as free radicals. Vitamin E neutralizes peroxides, which result from the free radical oxidation of lipids, making it a key antioxidant in cell membranes. While d-alpha tocopherol has generally been regarded as the form of vitamin E with the strongest antioxidant activity, tocotrienols are even stronger.

The tocotrienol story is another example of a natural product slow to gain recognition. A Univeristy of California research team discovered that d-alpha tocotrienol is over six times more effective than d-alpha tocopherol at protecting cell membranes against free radical damage.13 In the presence of vitamin C, which recycles vitamin E-like compounds, its antioxidant activity is 40 to 60 times higher than d-alpha tocopherol. This study was published in 1991. Its safe to say few cardiac physicians know about tocotrienols, and we have yet to see 60 Minutes do a piece on "the powerful new form of vitamin E."

It would be a tremendous service to public health if they did, because the benefits of tocotrienols go far beyond their stellar antioxidant ability. Tocotrienols also lower total cholesterol and LDL, by impressive percentages. In one double-blind controlled study, tocotrienols reduced total cholesterol by 16 percent and LDL by 21 percent after twelve weeks. Another study recorded drops of 15 to 22 percent in total cholesterol along with 10 to 20 percent decreases in LDL levels.14 Now appearing on health food store shelves, tocotrienols are a health-protecting nutrients whose long overdue time has come. Derived from food oils such as palm oil and rice bran oil, tocotrienols have the same lack of toxicity as ordinary vitamin E.

References

1. Satyavati, G. Gugulipid: a promising hypolipidaemic agent from gum guggul (Commiphora wightii). Economic and Medicinal Plant Research 1991;5:47-82.

2. Dev, S. A modern look at an age-old Ayurvedic drug—guggulu. Science Age July 1987:13-18.

3. Nityanand, S., Srivastava, J.S., Asthana, O.P. Clinical trials with gugulipid. J. Ass. Physicians of India 1989;37(5):323-28.

4. Agarwal, R.C. et. al. Clinical trial of gugulipid—a new hypolipidemic agent of plant origin in primary hyperlipidemia. Indian J Med Res 1986;84:626-34.

5. 'Gugulipid' Drugs of the Future 1988;13(7):618-619.

6. Maggi, G.C., Donati, C., Criscuoli, G. Pantethine: A physiological lipomodulating agent, in the treatment of hyperlipidemias. Current Therapeutic Research 1982;32(3):380-86.

7. Kimura, S., Furukawa, Y., Wakasugi, J. Effects of pantethine on the serum lipoprotiens in rats fed a high cholesterol diet (Abstract) Seventh International Symposium on Drugs Affecting Lipid Metabolism, Milan, Italy, 1980.

8. Arsenio, L. Bodria, P. Effectiveness of long-term treatment with pantethine in patients with dyslipidemia. Clinical Therapeutics 1986;8(5):537-45.

9. Avogaro, P. Bittolo Bon, G. Fusello, M. Effect of pantethine on lipids, lipoproteins and apolipoproteins in man. Current Therapeutic Research 1983;33(3):488-93.

10. Crouse, J.R. New developments in the use of niacin for treatment of hyperlipidemia: new considerations in the use of an old drug. Coronary Artery Disease 1996;7(4):321-26.

11. Welsh, A.L. Ede, M. Inositol hexanicotinate for improved nicotinic acid therapy. International Record of Food Medicine 1961;174(1):9-15.

12. "Inositol hexaniacinate" (Monograph). Alternative Medicine Review 1998;3(3):222-3.

13. Serbinova, E., et. al. Free radical recycling and intramembrane mobility in the antioxidant properties of alpha-tocopherol and alpha tocotrienol. Free Radical Biology and Medicine 1991;10:263-275.

14. Qureshi, N. Qureshi, A.A. Tocotrienols: Novel Hypercholesterolemic Agents with Antioxidant Properties. in 'Vitamin E in Health and Disease' Lester Packer and Jürgen Fuchs, Editors. 1993; New York: Marcel Dekker, Inc.

Control Cholesterol with the following Supplements