RE: lowering total cholesterol

[Guest guest]

Things associated with lower LDL and increased HDL include lower carb diets,

alcohol consumption, and niacin, among others, including exercise.

>From: " Berkovitz " <michelleberkovitz@...>

>Reply-

>

>Subject: [ ] lowering total cholesterol

>Date: Thu, 29 Jul 2004 02:15:15 -0000

>

>I need help planning some dietary changes for my non-CRON husband,

>whose cholesterol is creeping too high. He continues to claim that

>if he could just get more exercise he can push it back down from 204

>to 180, where it used to be in his early 40s. He's 48 now. HDL is 66

>and LDL is 129.

>

>I myself at age 46 have maintained total cholesterol at 140 since I

>began getting it measured in my 20s, but it's partly genetic good

>luck, I think.

>

>I welcome any and all suggestions. I have not yet begun to research

>this, because I thought someone here probably has a quick list of

>good stuff to eat and bad stuff to eat, along with ideas about

>supplementation. I've been subscribed to this list for just a couple

>of months, so I still have more searching to do in the archives for

>ideas. Looking for a shortcut here.

>

>Thanks,

>

>

[Guest guest]

>>Things associated with lower LDL and increased HDL include lower carb diets,

In the 2 most recent studies on low carb diets, 30% of the subjects experienced

and increase in LDL of over 10% or more and 2 of them died during the study. In

the Duke University study, two thirds of the low carb dieters reported

constipation problems, 60% reported headaches, and 25% complained of a general

feeling of weakness. The low carb dieters were five times more likely to suffer

from muscle cramps compared to the low-fat dieters, and three times more likely

to have diarrhea.

In study were subjects were followed for 2 years who were not losing weight,

who were on low carb diets, LDLs went up over 30% .

just showed that a higher carb diet, based on unrefined whole foods,

(with plant sterols and soluble fiber) lowered LDL 29%. The effect of the plant

sterols and soluble fiber supplements is estimated to be about 10-15%. So,

15-20% was due to the diet.

>>alcohol consumption,

May raise HDL but wont lower LDL

Removing refined carbs (white flour, white sugar, etc) is beneficial.

Jeff

[Guest guest]

>>>In study were subjects were followed for 2 years who were not losing weight, who were on low carb diets, LDLs went up over 30% .

JAMA, 2003. 290: 912-920. At the beginning of the study and then 6 months, 12 months, and 24 months later, the s Hopkins

researchers took blood measurements . After just six months, the low carb ketogenic diet significantly increased both total and LDL

cholesterol. Total cholesterol shot up from an average 174 to 232. LDL rose from 99 to 148. Triglycerides went up 60%, from 96 to 154. HDL, the good

cholesterol, fell from 56 to 49. Adverse changes in blood lipid levels persisted after 12 and 24 months.

Also.....

In the August 2002 in Preventive Cardiology. Scientists assigned 100 overweight men and women to one of four diets, one of which was a low carbohydrate

diet. After one year, the men and women on the low-carb diet lost weight (13% of their body weight), but

at the price of increased cardiovascular risk factors. Triglycerides rose, as did LDL cholesterol, total cholesterol, clotting factors, and homocysteine levels and their HDLs fell.

[Guest guest]

J Nutr. 2003 Sep;133(9):2756-61.

Related Articles,

Links

An isoenergetic very low carbohydrate diet improves serum HDL cholesterol and triacylglycerol concentrations, the total cholesterol to HDL cholesterol ratio and postprandial pipemic responses compared with a low fat diet in normal weight, normolipidemic women.Volek JS, Sharman MJ, Gomez AL, Scheett TP, Kraemer WJ.Department of Kinesiology, University of Connecticut, Storrs, CT 06269-1110, USA. jvolek@...Very low carbohydrate diets are popular, yet little is known about their effects on blood lipids and other cardiovascular disease risk factors. We reported previously that a very low carbohydrate diet favorably affected fasting and postprandial triacylglycerols, LDL subclasses and HDL cholesterol (HDL-C) in men but the effects in women are unclear. We compared the effects of a very low carbohydrate and a low fat diet on fasting lipids, postprandial lipemia and markers of inflammation in women. We conducted a balanced, randomized, two-period, crossover study in 10 healthy normolipidemic women who consumed both a low fat (<30% fat) and a very low carbohydrate (<10% carbohydrate) diet for 4 wk each. Two blood draws were performed on separate days at 0, 2 and 4 wk and an oral fat tolerance test was performed at baseline and after each diet period. Compared with the low fat diet, the very low carbohydrate diet increased (P <or= 0.05) fasting serum total cholesterol (16%), LDL cholesterol (LDL-C) (15%) and HDL-C (33%) and decreased serum triacylglycerols (-30%), the total cholesterol to HDL ratio (-13%) and the area under the 8-h postprandial triacylglycerol curve (-31%). There were no significant changes in LDL size or markers of inflammation (C-reactive protein, interleukin-6, tumor necrosis factor-alpha) after the very low carbohydrate diet. In normal weight, normolipidemic women, a short-term very low carbohydrate diet modestly increased LDL-C, yet there were favorable effects on cardiovascular disease risk status by virtue of a relatively larger increase in HDL-C and a decrease in fasting and postprandial triaclyglycerols.Publication Types:

Clinical Trial Randomized Controlled Trial PMID: 12949361 [PubMed - indexed for MEDLINE]

J Nutr. 2004 Apr;134(4):880-5. Related Articles, Links

Very low-carbohydrate and low-fat diets affect fasting lipids and postprandial lipemia differently in overweight men.

Sharman MJ, Gomez AL, Kraemer WJ, Volek JS.

Department of Kinesiology, University of Connecticut, Storrs, CT 06269-1110, USA. matthew.sharman@...

Hypoenergetic very low-carbohydrate and low-fat diets are both commonly used for short-term weight loss; however, few studies have directly compared their effect on blood lipids, with no studies to our knowledge comparing postprandial lipemia, an important independently identified cardiovascular risk factor. The primary purpose of this study was to compare the effects of a very low-carbohydrate and a low-fat diet on fasting blood lipids and postprandial lipemia in overweight men. In a balanced, randomized, crossover design, overweight men (n = 15; body fat >25%; BMI, 34 kg/m(2)) consumed 2 experimental diets for 2 consecutive 6-wk periods. One was a very low-carbohydrate (<10% energy as carbohydrate) diet and the other a low-fat (<30% energy as fat) diet. Blood was drawn from fasting subjects on separate days and an oral fat tolerance test was performed at baseline, after the very low-carbohydrate diet period, and after the low-fat diet period. Both diets had the same effect on serum total cholesterol, serum insulin, and homeostasis model analysis-insulin resistance (HOMA-IR). Neither diet affected serum HDL cholesterol (HDL-C) or oxidized LDL (oxLDL) concentrations. Serum LDL cholesterol (LDL-C) was reduced (P < 0.05) only by the low-fat diet (-18%). Fasting serum triacylglycerol (TAG), the TAG/HDL-C ratio, and glucose were significantly reduced only by the very low-carbohydrate diet (-44, -42, and -6%, respectively). Postprandial lipemia was significantly reduced when the men consumed both diets compared with baseline, but the reduction was significantly greater after intake of the very low-carbohydrate diet. Mean and peak LDL particle size increased only after the very low-carbohydrate diet. The short-term hypoenergetic low-fat diet was more effective at lowering serum LDL-C, but the very low-carbohydrate diet was more effective at improving characteristics of the metabolic syndrome as shown by a decrease in fasting serum TAG, the TAG/HDL-C ratio, postprandial lipemia, serum glucose, an increase in LDL particle size, and also greater weight loss (P < 0.05).

Publication Types:

Clinical Trial Randomized Controlled Trial

PMID: 15051841 [PubMed - indexed for MEDLINE]

>From: "Jeff Novick"

>Reply- >

>Subject: RE: [ ] lowering total cholesterol >Date: Thu, 29 Jul 2004 10:55:14 -0400 > > >>>In study were subjects were followed for 2 years who were not >losing weight, who were on low carb diets, LDLs went up over 30% . > >JAMA, 2003. 290: 912-920. At the beginning of the study and then 6 >months, 12 months, and 24 months later, the s Hopkins > >researchers took blood measurements . After just six months, the low >carb ketogenic diet significantly increased both total and LDL > >cholesterol. Total cholesterol shot up from an average 174 to 232. LDL >rose from 99 to 148. Triglycerides went up 60%, from 96 to 154. HDL, the >good > >cholesterol, fell from 56 to 49. Adverse changes in blood lipid levels >persisted after 12 and 24 months. > > > >Also..... > >In the August 2002 in Preventive Cardiology. Scientists assigned 100 >overweight men and women to one of four diets, one of which was a low >carbohydrate > >diet. After one year, the men and women on the low-carb diet lost >weight (13% of their body weight), but > >at the price of increased cardiovascular risk factors. Triglycerides >rose, as did LDL cholesterol, total cholesterol, clotting factors, and >homocysteine levels and their HDLs fell. > >

[Guest guest]

Many studies have also shown beneficial effects on lipid profile and insulin sensitivity with low carb diets. My own experience on a non-weight reducing low carb diet was that my total cholesterol increased from that of my prior low fat diet. To wit: my low fat diet lipids TC= 113 mg/dl, HDL = 55 mg/dl. Low carb diet TC= 155 mg/dl, HDL = 105 mg/dl, LDL = 36 mg/dl.

To be sure, individuals will experience different outcomes, and one's lipid parameters and overall health and satisfaction need to be incorporated with any changes made in diet and lifestyle.

I did not stay on a very strict low carb diet for long, and have since drifted into a mostly raw vegetable, fruit, and lean protein diet with some nuts and seeds and cereal fibers (All Bran Extra Fiber cereal, for instance.)

I agree any diet should minimize if not eliminate refined carbohydrates and emphasize fresh vegetables, fresh fruit, and whole grains.

>From: "Jeff Novick" <jnovick@...> >Reply- >< > >Subject: RE: [ ] lowering total cholesterol >Date: Thu, 29 Jul 2004 09:44:23 -0400 > > >>Things associated with lower LDL and increased HDL include lower carb diets, > >In the 2 most recent studies on low carb diets, 30% of the subjects experienced and increase in LDL of over 10% or more and 2 of them died during the study. In the Duke University study, two thirds of the low carb dieters reported constipation problems, 60% reported headaches, and 25% complained of a general feeling of weakness. The low carb dieters were five times more likely to suffer from muscle cramps compared to the low-fat dieters, and three times more likely to have diarrhea. > >In study were subjects were followed for 2 years who were not losing weight, who were on low carb diets, LDLs went up over 30% . > > just showed that a higher carb diet, based on unrefined whole foods, (with plant sterols and soluble fiber) lowered LDL 29%. The effect of the plant sterols and soluble fiber supplements is estimated to be about 10-15%. So, 15-20% was due to the diet. > > >>alcohol consumption, > >May raise HDL but wont lower LDL > >Removing refined carbs (white flour, white sugar, etc) is beneficial. > >Jeff > > ><< winmail.dat >>

[Guest guest]

>> I agree any diet should minimize if not eliminate refined carbohydrates and emphasize fresh vegetables, fresh fruit, and whole grains.

Ditto!

[Guest guest]

In order of importance:

1. Avoid ingesting all deadly trans-fats, isolated fructose and high-

insulinic carbohydrates.

2. Correct hormonal imbalance with bio-identical hormone therapy.

3. Ingest soluble fiber, pharmaceutical-grade fish oil, mixed natural

vitamin E, policosanol, artichoke leaf extract, aged garlic extract,

curcumin, gugulipid, green tea, flushful niacin, flax seed oil, soy.

The last three should be taken with caution.

Logan

> I welcome any and all suggestions. I have not yet begun to research

> this, because I thought someone here probably has a quick list of

> good stuff to eat and bad stuff to eat, along with ideas about

> supplementation. I've been subscribed to this list for just a

couple

> of months, so I still have more searching to do in the archives for

> ideas. Looking for a shortcut here.

[Guest guest]

Hi folks:

And just to be clear about the potential for bias in these

studies ......... CUBA??? Policosanol can be made from SUGAR

CANE??? (Pretty much Cuba's only export).

Of course this doesn't PROVE bias, but ..........

The Cuban studies also claimed a fairly sizeable rise in HDL. So it

may be worth watching to see if studies done by serious sources on

this substance come to similar conclusions, and prove it to be safe

also.

Rodney.

--- In , " Jeff Novick " <jnovick@p...>

wrote:

> >>policosanol,

>

> Policosanol lowered LDL by 17 to 31 percent in 19 trials involving

more than 1,900 people. But 16 of the studies were carried out by

just one group of researchers in Havana, Cuba. (The other three were

small trials done in Mexico, Argentina, and Chile.) Policosanol has

never been tested in good studies in the U.S., Canada, Europe, or

Japan. What's more, the policosanol used in most U.S. supplements

(including the reformulated` Cholestin) is extracted from beeswax,

not sugarcane. Beeswax policosanol hasn't been tested on cholesterol

levels.

[Guest guest]

I don't have time to post abstracts for every treatment approach, so

I'll post some for the lesser-known.

Logan

HORMONAL IMBALANCE

Hypercholesterolemia treatment: a new hypothesis or just an accident?

Dzugan SA, Arnold R.

North Central Mississippi Regional Cancer Center, Greenwood,

Mississippi 38935-0549, USA. sdzugan@...

Med Hypotheses. 2002 Dec;59(6):751-6.

A new hypothesis concerning the association of low levels of steroid

hormones and hypercholesterolemia is proposed. This study presents

data that concurrent restoration to youthful levels of multiple

normally found steroid hormones is able to normalize or improve serum

total cholesterol (TC). We evaluated 20 patients with

hypercholesterolemia who received hormonorestorative therapy (HT)

with natural hormones. Hundred percent of patients responded. Mean

serum TC was 263.5 mg/dL before and 187.9 mg/dL after treatment.

Serum TC dropped below 200 mg/dL in 60.0%. No morbidity or mortality

related to HT was observed. In patients characterized by

hypercholesterolemia and sub-youthful serum steroidal hormones, our

findings support the hypothesis that hypercholesterolemia is a

compensatory mechanism for life-cycle related down-regulation of

steroid hormones, and that broadband steroid hormone restoration is

associated with a substantial drop in serum TC in many patients.

---

Hormone replacement therapy in postmenopausal women and its effects

on plasma lipid levels.

Erberich LC, Alcantara VM, Picheth G, Scartezini M.

Laboratory Laborfoz, Foz do Iguacu, PR, Brazil.

Clin Chem Lab Med. 2002 May;40(5):446-51.

Postmenopausal women run the same risks of coronary heart disease as

men. The lipid alterations observed at this time reflect increased

blood levels of total cholesterol, low-density lipoprotein

cholesterol (LDL-C) and lipoprotein (a), and reduced high-density

lipoprotein cholesterol (HDL-C) levels. These changes lead to a

higher risk of coronary artery disease, and hormonal therapy has a

favorable effect on lipid metabolism. In this paper we review the

literature on hormone replacement therapy (HRT) in postmenopausal

women with the emphasis on the role of lipids in the pathogenesis of

coronary heart disease, and on the action of estrogens and their

correlation with progestogens, as well as routes of HRT

administration. We conclude that the HRT changes the lipid profile in

a potentially anti-atherogenic direction, usually reducing LDL-C and

increasing HDL-C and triglycerides. Otherwise, for postmenopausal

women with established coronary disease HRT is not recommended.

---

Effects of hormone replacement therapy on serum lipids in elderly

women. a randomized, placebo-controlled trial.

Binder EF, DB, Schechtman KB, Jeffe DB, Kohrt WM.

Division of Geriatrics and Gerontology, Washington University School

of Medicine, 4488 Forest Park Boulevard, Suite 201, St. Louis, MO

63108, USA.

Ann Intern Med. 2001 May 1;134(9 Pt 1):754-60.

BACKGROUND: Coronary heart disease (CHD) is the leading cause of

death among older women. In observational studies, the incidence of

CHD has been reduced in postmenopausal women who take hormone

replacement therapy (HRT). A low serum level of high-density

lipoprotein (HDL) cholesterol is one of the risk factors predictive

of death from CHD. OBJECTIVE: To determine the effects of HRT on

serum lipid and lipoprotein levels in elderly women. DESIGN:

Randomized, double-blind, placebo-controlled trial. SETTING:

University research center. PARTICIPANTS: 59 sedentary women 75 years

of age or older. INTERVENTION: Participants were assigned to 9 months

of oral therapy with placebo or conjugated estrogens, 0.625 mg/d,

plus trimonthly medroxyprogesterone acetate, 5 mg/d for 13 days.

MEASUREMENTS: Serum lipid and lipoprotein levels. RESULTS: After 9

months of treatment, women in the HRT group compared with women in

the placebo group had decreased low-density lipoprotein cholesterol

levels (mean change [+/-SD], -0.47 +/- 0.69 mmol/L [-18.2 +/- 26.5

mg/dL] vs. -0.06 +/- 0.32 mmol/L [-2.2 +/- 12.2 mg/dL], respectively;

between-group difference, 0.41 mmol/L [95% CI, 0.09 to 0.74 mmol/L],

16 mg/dL [95% CI, 3.5 to 28.5 mg/dL]; P = 0.01) and increased HDL

cholesterol levels (mean change, 0.21 +/- 0.27 mmol/L [8.1 +/- 10.5

mg/dL] vs. 0.06 +/- 0.11 mmol/L [2.4 +/- 4.3 mg/dL], respectively;

between-group difference, 0.15 mmol/L [CI, 0.008 to 0.29 mmol/L], 5.7

mg/dL [CI, 0.8 to 10.6 mg/dL]; P = 0.02). The observed changes were

independent of age at menopause onset, baseline lipid values, body

weight, waist circumference, percentage body fat, and peak aerobic

power. CONCLUSIONS: In women 75 years of age or older, HRT improved

the lipoprotein profile to the extent observed previously in younger

postmenopausal women. Further studies are needed to evaluate whether

these effects protect against CHD in this population.

---

Cholesterol and lipoprotein metabolism in aging: reversal of

hypercholesterolemia by growth hormone treatment in old rats.

Parini P, Angelin B, Rudling M.

Metabolism Unit, Center for Metabolism and Endocrinology, Department

of Medicine, Karolinska Institute at Huddinge University Hospital,

Huddinge, Sweden.

Arterioscler Thromb Vasc Biol. 1999 Apr;19(4):832-9.

Plasma cholesterol levels increase with age, as does the incidence of

coronary heart disease. The mechanisms responsible for the age-

related hypercholesterolemia are not well understood. An interesting

hypothesis suggests that the relative deficiency in growth hormone

(GH), which occurs with aging, contributes to the development of the

age-related hypercholesterolemia, because GH has beneficial effects

on cholesterol metabolism. In the present work, we tested this

hypothesis by the administration of GH to normal rats of varying

ages. Plasma lipids and hepatic cholesterol metabolism were

characterized in 2-, 12-, and 18-month-old male Sprague-Dawley rats.

In 2-month-old rats, GH specifically stimulated the hepatic low

density lipoprotein (LDL) receptor expression in a dose-dependent

way, both at the protein level and at the mRNA level. Concomitantly,

plasma cholesterol increased by approximately 30% within the large

high density lipoprotein and LDL fractions. In 12-month-old animals,

cholesterol 7alpha-hydroxylase (C7alphaOH) activity was reduced,

whereas hepatic LDL receptors and plasma total cholesterol were

unchanged. GH treatment (1 mg. kg-1. d-1) normalized the activity of

C7alphaOH and had effects on plasma cholesterol and LDL receptors

similar to those seen in 2-month-old animals. In 18-month-old rats,

plasma cholesterol was increased 2-fold, whereas hepatic LDL receptor

expression and C7alphaOH activity were similar to those of the 12-

month-old animals. Infusion of GH to 18-month-old rats had similar

effects on hepatic C7alphaOH and LDL receptors as seen in 12-month-

old rats. However, GH treatment strongly reduced the

hypercholesterolemia in 18-month-old animals. We conclude that the

age-dependent increase of plasma cholesterol in rats can be reversed

by the administration of GH, presumably through the pleiotropic

effects of this hormone on lipoprotein metabolism.

---

Metabolic effect of two hormonal preparations in postmenopausal women.

Bissonnette F, Lussier-Cacan S, Fugere P, Berube S.

Department of Obstetrics and Gynecology, Universite de Montreal,

Hopital Saint-Luc, Quebec, Canada.

Maturitas. 1997 Jul;27(3):275-84.

OBJECTIVES: To compare the metabolic and endocrinological effects of

estradiol valerate/cyproterone acetate (EV/CPA) to a regimen of

conjugated estrogens/medroxyprogesterone acetate (CE/MPA) in

postmenopausal women. METHODS: Lipid profile, endocrinological

parameters, coagulation factors, renin and angiotensinogen were

followed in postmenopausal women randomized to EV/CPA or CE/MPA

during 12 cycles. RESULTS: Following 12 cycles of treatment, total

plasma cholesterol decreased more with EV/CPA than with CE/MPA. Low-

density cholesterol decreased with EV/CPA while it increased with

CE/MPA. High-density cholesterol remained fairly unchanged, and

triglycerides increased significantly in both groups. Estradiol and

estrone levels increased significantly more with EV/CPA than with

CE/MPA while the sex-hormone-binding globulin increased more with

CE/MPA. Follicle stimulating and luteinizing hormone levels also

decreased significantly. Total testosterone and

dihydroepiandrosterone sulfate remained stable. Total levothyroxine

serum levels increased significantly, but thyroid stimulating hormone

and triiodothyronine levels remained stable. Coagulation parameters

also remained stable. Angiotensinogen increased, while plasma renin

activity and blood pressure remained unchanged. CONCLUSION: It is

concluded that both EV/CPA and CE/MPA produce favourable metabolic

effects. A better lipid profile, compatible with decreased

cardiovascular risk, is observed with the EV/CPA regimen. Higher

circulating estrogen levels may explain in part this observation.

---

Modulation of very low density lipoprotein production and clearance

contributes to age- and gender- dependent hyperlipoproteinemia in

apolipoprotein E3-Leiden transgenic mice.

van Vlijmen BJ, van 't Hof HB, Mol MJ, van der Boom H, van der Zee A,

Frants RR, Hofker MH, Havekes LM.

TNO Prevention and Health, Gaubius Laboratory, Leiden, The

Netherlands.

J Clin Invest. 1996 Mar 1;97(5):1184-92.

Apolipoprotein E3-Leiden (APOE*3-Leiden) transgenic mice have been

studied to identify factors modulating chylomicron and VLDL remnant

lipoprotein metabolism. Transient elevated levels of VLDL/LDL-sized

lipoproteins occurred in these mice with maximal levels during the

period of rapid growth (optimum at 45 d of age). After about 100 d of

age, serum cholesterol and triglyceride levels stabilized to slightly

elevated levels as compared to control mice. The expression of the

APOE*3-Leiden transgene was not age-dependent. In young mice the in

vivo hepatic production of VLDL-triglycerides was 50% increased as

compared to older mice. This is sustained by in vivo VLDL-apo B

turnover studies showing increased (75%) VLDL-apo B secretion rates

in young mice, whereas the VLDL-apo B clearance rate appeared not to

be age dependent. On a high fat/cholesterol diet, females displayed

significantly higher cholesterol levels than males (10 versus 7.0

mmol/liter, respectively). Serum levels of VLDL/LDL sized

lipoproteins increased upon administration of estrogens, whereas

administration of testosterone gave the opposite result. As compared

to male mice, in female mice the hepatic VLDL-triglyceride production

rate was significantly elevated. Injection of estrogen in males also

resulted in increased VLDL-triglyceride production, although not

statistically significant. In vivo VLDL-apo B turnover experiments

showed that the VLDL secretion rate tended to be higher in females.

Although, the fractional catabolic rate of VLDL-apo B is not

different between males and females, administration of estrogens in

males resulted in a decreased clearance rate of VLDL, whereas

administration of testosterone in females resulted in an increased

clearance rate of VLDL. The latter presumably due to an inhibiting

effect of testosterone on the expression of the APOE*3-Leiden

transgene. We conclude that hyperlipidemia in APOE*3-Leiden

transgenic mice is strongly affected by age via its effect on hepatic

VLDL production rate, whereas gender influences hyperlipidemia by

modulating both hepatic VLDL production and clearance rate.

POLICOSANOL

Role of policosanols in the prevention and treatment of

cardiovascular disease.

Varady KA, Wang Y, PJ.

School of Dietetics and Human Nutrition, McGill University, Ste-Anne-

de-Bellevue, Quebec, Canada.

Nutr Rev. 2003 Nov;61(11):376-83.

Policosanols are a mixture of aliphatic alcohols derived from

purified sugar cane. When administered at 5 to 20 mg/day,

policosanols have been shown to decrease the risk of atheroma

formation by reducing platelet aggregation, endothelial damage, and

foam cell formation in animals. Additionally, policosanols have been

shown to lower total and low-density lipoprotein (LDL) cholesterol

levels by 13 to 23% and 19 to 31%, respectively, while increasing

high-density lipoprotein (HDL) cholesterol from 8 to 29%.

Policosanols are thought to improve lipid profiles by reducing

hepatic cholesterol biosynthesis while enhancing LDL clearance. When

compared with statins, policosanols exhibit comparable cholesterol-

lowering effects at much smaller doses. The mixture is well tolerated

when administered to animals; however, a more precise safety profile

is needed for humans. In summary, policosanols are a promising

resource in the prevention and therapy of cardiovascular disease

(CVD), but these results need to be confirmed in independent

laboratories.

---

Comparison of the efficacy and tolerability of policosanol with

atorvastatin in elderly patients with type II hypercholesterolaemia.

Castano G, Mas R, Fernandez L, Illnait J, Mesa M, Alvarez E, Lezcay M.

Medical Surgical Research Center, Havana City, Cuba.

Drugs Aging. 2003;20(2):153-63.

BACKGROUND: Hypercholesterolaemia is a risk factor for coronary heart

disease (CHD). Clinical studies have shown that lowering elevated

serum total cholesterol (TC) levels, and particularly low density

lipoprotein-cholesterol (LDL-C) levels, reduces the frequency of

coronary morbidity and deaths, whereas high serum levels of high

density lipoprotein-cholesterol (HDL-C) protect against CHD.

Policosanol is a cholesterol-lowering drug purified from sugar cane

wax with a therapeutic dosage range from 5-20 mg/day. Atorvastatin is

an HMG-CoA reductase inhibitor which across its dosage range (10-80

mg/day) has shown significantly greater lipid-lowering effects than

all previously marketed statins. OBJECTIVE: This study was undertaken

to compare the efficacy and tolerability of policosanol with

atorvastatin in older patients with type II hypercholesterolaemia.

PATIENTS AND METHODS: This randomised, single-blind, parallel-group

study was conducted in older patients (60-80 years) with type II

hypercholesterolaemia. After 4 weeks on a cholesterol-lowering diet,

75 patients were randomised to policosanol or atorvastatin 10mg

tablets taken once daily with the evening meal for 8 weeks. An

interim and final check-up were performed at 4 and 8 weeks,

respectively, after treatment was initiated. RESULTS: At 4 (p <

0.0001) and 8 (p < 0.00001) weeks, policosanol 10 mg/day

significantly lowered serum LDL-C levels by 17.5 and 23.1%,

respectively compared with baseline; corresponding values for

atorvastatin were 28.4 and 29.8%. At study completion, policosanol

significantly (p < 0.0001) reduced serum TC (16.4%), LDL-C/HDL-C

ratio (25.5%) and TC/HDL-C ratio (19.3%), as well as (p < 0.001)

triglyceride levels (15.4%). Atorvastatin significantly (p < 0.0001)

decreased serum TC (22.6%), LDL-C/HDL-C (26.2%) and TC/HDL-C (19.8%)

ratios, as well as (p < 0.001) triglyceride levels (15.5%).

Atorvastatin was significantly more effective than policosanol in

reducing LDL-C and TC, but similar in reducing both atherogenic

ratios and triglyceride levels. Policosanol, but not atorvastatin,

significantly (p < 0.05) increased serum HDL-C levels by 5.3%. Both

treatments were well tolerated. At study completion, atorvastatin

mildly, but significantly (p < 0.05) increased creatine phosphokinase

(CPK) and creatinine, whereas policosanol significantly reduced AST

and glucose (p < 0.01) and CPK (p < 0.05) levels. All individual

values, however, remained within normal limits. Three atorvastatin

but no policosanol patients withdrew from the study because of

adverse events: muscle cramps (1 patient), gastritis (1 patient) and

uncontrolled hypertension, abdominal pain and myalgia (1 patient).

Overall, no policosanol and seven atorvastatin patients (18.9%)

reported a total of nine mild or moderate adverse events during the

study (p < 0.01). CONCLUSIONS: This study shows that policosanol (10

mg/day) administered for 8 weeks was less effective than atorvastatin

(10 mg/day) in reducing serum LDL-C and TC levels in older patients

with type II hypercholesterolaemia. Policosanol, but not

atorvastatin, however, significantly increased serum HDL-C levels,

whereas both drugs similarly reduced atherogenic ratios and serum

triglycerides. Policosanol was better tolerated than atorvastatin as

revealed by patient withdrawal analysis and overall frequency of

adverse events. Nevertheless, further studies must be conducted in

larger sample sizes and using dose-titration methods to achieve

target lipid levels in order to reach wider conclusions.

---

Policosanol safely down-regulates HMG-CoA reductase - potential as a

component of the Esselstyn regimen.

McCarty MF.

Pantox Laboratories, San Diego 92109, USA.

Med Hypotheses. 2002 Sep;59(3):268-79.

Many of the wide-ranging health benefits conferred by statin therapy

are mediated, not by reductions in LDL cholesterol, but rather by

inhibition of isoprenylation reactions essential to the activation of

Rho family GTPases; this may be the mechanism primarily responsible

for the favorable impact of statins on risk for ischemic stroke,

senile dementia, and fractures, as well as the anti-hypertensive and

platelet-stabilizing actions of these drugs. Indeed, the extent of

these benefits is such as to suggest that most adults would be wise

to take statins; however, owing to the significant expense of statin

therapy, as well as to the potential for dangerous side effects that

mandates regular physician follow-up, this strategy appears

impractical. However, policosanol, a mixture of long-chain aliphatic

alcohols extractable from sugar cane wax, has shown cholesterol-

lowering potency comparable to that of statins, and yet appears to be

devoid of toxic risk. Recent evidence indicates that policosanol down-

regulates cellular expression of HMG-CoA reductase, and thus has the

potential to suppress isoprenylation reactions much like statins do.

Consistent with this possibility, the results of certain clinical and

animal studies demonstrate that policosanol has many effects

analogous to those of statins that are not likely explained by

reductions of LDL cholesterol. However, unlike statins, policosanol

does not directly inhibit HMG-CoA reductase, and even in high

concentrations it fails to down-regulate this enzyme by more than

50% - thus likely accounting for the safety of this nutraceutical. In

light of the fact that policosanol is quite inexpensive and is

becoming available as a non-prescription dietary supplement, it may

represent a practical resource that could enable the general public

to enjoy health benefits comparable to those conferred by statins. In

a long-term clinical study enrolling patients with significant

symptomatic coronary disease, Esselstyn has demonstrated that a low-

fat, whole-food vegan diet, coupled with sufficient statin therapy to

maintain serum cholesterol below 150 mg/dL, can stop the progression

of coronary disease and virtually eliminate further risk for heart

attack. A comparable regimen, in which policosanol is used in place

of statins, may represent a practical strategy whereby nearly

everyone willing to commit to health-protective eating can either

prevent coronary disease, or prevent pre-existing coronary disease

from progressing to a life-threatening event.

---

Policosanol: clinical pharmacology and therapeutic significance of a

new lipid-lowering agent.

Gouni-Berthold I, Berthold HK.

Medical Policlinic, University of Bonn, Bonn, Germany. berthold@uni-

bonn.de

Am Heart J. 2002 Feb;143(2):356-65.

BACKGROUND: Policosanol is a mixture of higher primary aliphatic

alcohols isolated from sugar cane wax, whose main component is

octacosanol. The mixture has been shown to lower cholesterol in

animal models, healthy volunteers, and patients with type II

hypercholesterolemia. METHODS: We reviewed the literature on placebo-

controlled lipid-lowering studies using policosanol published in peer-

reviewed journals as well as studies investigating its mechanism of

action and its clinical pharmacology. RESULTS: At doses of 10 to 20

mg per day, policosanol lowers total cholesterol by 17% to 21% and

low-density lipoprotein (LDL) cholesterol by 21% to 29% and raises

high-density lipoprotein cholesterol by 8% to 15%. Because higher

doses have not been tested up to now, it cannot be excluded that

effectiveness may be even greater. Daily doses of 10 mg of

policosanol have been shown to be equally effective in lowering total

or LDL cholesterol as the same dose of simvastatin or pravastatin.

Triglyceride levels are not influenced by policosanol. At dosages of

up to 20 mg per day, policosanol is safe and well tolerated, as

studies of >3 years of therapy indicate. There is evidence from in

vitro studies that policosanol may inhibit hepatic cholesterol

synthesis at a step before mevalonate generation, but direct

inhibition of the hydroxy-methylglutaryl-coenzyme A reductase is

unlikely. Animal studies suggest that LDL catabolism may be enhanced,

possibly through receptor-mediated mechanisms, but the precise

mechanism of action is not understood yet. Policosanol has additional

beneficial properties such as effects on smooth muscle cell

proliferation, platelet aggregation, and LDL peroxidation. Data on

efficacy determined by clinical end points such as rates of cardiac

events or cardiac mortality are lacking. CONCLUSIONS: Policosanol

seems to be a very promising phytochemical alternative to classic

lipid-lowering agents such as the statins and deserves further

evaluation.

---

Efficacy and tolerability of policosanol in hypercholesterolemic

postmenopausal women.

Mirkin A, Mas R, to M, Boccanera R, is A, Poudes R,

Fuster A, Lastreto E, Yanez M, Irico G, McCook B, Farre A.

Eva Peron Hospital, rio, Argentina.

Int J Clin Pharmacol Res. 2001;21(1):31-41.

This randomized, double-blind, multicenter placebo-controlled study

was conducted to investigate the efficacy and tolerability of

policosanol, a cholesterol-lowering drug purified from sugar cane

wax, in women who had experienced menopause and showed elevated serum

total cholesterol and low density lipoprotein (LDL)-cholesterol

levels despite a 6-week standard lipid-lowering diet. Thus, 56

eligible patients were randomized to receive placebo or policosanol 5

mg/day for 8 weeks and the dose was doubled to 10 mg/day during the

next 8 weeks. Policosanol (5 and 10 mg/day) significantly decreased

LDL-cholesterol (17.3% and 26.7%, respectively), total cholesterol

(12.9% and 19.5%) as well as the ratios of LDL-cholesterol to high-

density lipoprotein (HDL)-cholesterol (17.2% and 26.5%) and total

cholesterol to HDL-cholesterol (16.3% and 21.0%) compared with

baseline and placebo. HDL-cholesterol levels were significantly

raised by 7.4% at study completion. No significant changes occurred

in the lipid profile of the placebo group. The drug was safe and well

tolerated. No drug-related adverse effects were observed. None of the

patients administered policosanol but three of those administered

placebo withdrew from the trial because of adverse effects: one due

to a serious hypertensive status, one because of an allergic reaction

(pruritus plus skin rash) and one due to gastrointestinal

disturbances (nauseas plus vomiting). Eleven placebo patients

reported 24 adverse effects compared with six policosanol patients

who reported seven adverse effects (p < 0.05). In addition, five

placebo (17.9%) and 13 policosanol patients (46.4%) (p < 0.05)

reported improvements in habitual symptoms and health perception

during the study. In conclusion, policosanol was effective and well

tolerated in hypercholesterolemic postmenopausal women, showing

additional benefits in the health perception of the study patients.

---

A comparative study of policosanol Versus acipimox in patients with

type II hypercholesterolemia.

Alcocer L, Fernandez L, Campos E, Mas R.

Department of Cardiology, Mexico General Hospital, Mexico City.

Int J Tissue React. 1999;21(3):85-92.

An 8-week, randomized, double-blind study comparing the efficacy and

tolerability of policosanol and acipimox was conducted in patients

with type II hypercholesterolemia. Prior to entry into active

treatment, all patients followed a standard cholesterol-lowering diet

for 12 weeks. Sixty-three patients were randomized to receive either

policosanol (10 mg/day) or acipimox (750 mg/day) tablets for 8 weeks

under double-blind conditions. Both groups were similar at

randomization. Policosanol significantly reduced total cholesterol (p

< 0.0001) (15.8%), low-density lipoprotein (LDL)-cholesterol (21%)

and the ratios of LDL-cholesterol to high-density lipoprotein (HDL)-

cholesterol (15.8%) and cholesterol to HDL-cholesterol (11.5%).

Acipimox significantly lowered both cholesterol and LDL cholesterol

by 7.5%. The percent changes of total cholesterol, LDL-cholesterol

and both ratios were larger in the policosanol group than in the

acipimox group. Both drugs were well tolerated. Acipimox

significantly increased (p > 0.001) aspartate amino transferase

levels but only four patients showed increases above the normal

limit. Policosanol significantly reduced creatinine values (p > 0.05)

but no patients had values out of the normal range. Four patients

withdrew from the study (two from each group) but none withdrew

because of adverse effects. No adverse effects were reported in the

policosanol group, while five patients on acipimox reported adverse

effects (hot flushes, nausea, vomiting, headache, hypochondrial pain

and leg edema). These results indicate that policosanol (10 mg/day)

was more effective and well tolerated than was acipimox (750 mg/day)

in this study population.

---

[Comparative effects of policosanol and two HMG-CoA reductase

inhibitors on type II hypercholesterolemia]

[Article in Spanish]

Prat H, Roman O, Pino E.

Centro Cardiovascular Hospital Clinico Universidad de Chile.

Rev Med Chil. 1999 Mar;127(3):286-94.

BACKGROUND: Policosanol is a new cholesterol lowering agent derived

from sugar cane. AIM: To compare the cholesterol lowering efficacy of

policosanol with HMG CoA inhibitors. PATIENTS AND METHODS: Patients

with a LDL cholesterol over 160 mg/dl were studied. If, after 6 weeks

of diet, cholesterol persisted elevated, they were doubly blind

randomized to receive policosanol 10 mg/day (55 patients), lovastatin

20 mg/day (26 patients) or simvastatin 10 mg/day (25 patients). Serum

cholesterol was measured again after 8 weeks of therapy. RESULTS:

Initial demographic and laboratory data were similar among treatment

groups. A 24% LDL cholesterol reduction was obtained with

policosanol, compared with a 22% reduction with lovastatin and a 15%

reduction with simvastatin. HDL cholesterol significantly increased

in patients on policosanol and did not change in the other treatment

groups. Adverse effects of policosanol were mild and unspecific. No

changes in hepatic enzymes were observed. CONCLUSIONS: Policosanol is

a safe and effective cholesterol reducing agent.

ARTICHOKE LEAF

Flavonoids from artichoke (Cynara scolymus L.) upregulate eNOS gene

expression in human endothelial cells.

Li H, Xia N, Brausch I, Yao Y, Forstermann U.

Johannes Gutenberg University, Mainz, Germany.

J Pharmacol Exp Ther. 2004 May 3

Nitric oxide (NO) produced by endothelial NO synthase (eNOS)

represents an antithrombotic and anti-atherosclerotic principle in

the vasculature. Hence, an enhanced expression of eNOS in response to

pharmacological interventions could provide protection against

cardiovascular diseases. In EA.hy 926 cells, a cell line derived from

human umbilical vein endothelial cells (HUVEC), an artichoke leaf

extract (ALE) increased the activity of the human eNOS promoter

(determined by luciferase reporter gene assay). An organic sub-

fraction from ALE was more potent in this respect than the crude

extract, whereas an aqueous sub-fraction of ALE was without effect.

ALE and the organic sub-fraction thereof also increased eNOS mRNA

expression (measured by RNase protection assay) and eNOS protein

expression (determined by Western blot) both in EA.hy 926 cells and

in native HUVEC. NO production (measured by NO-ozone

chemiluminescence) was increased by both extracts. In organ chamber

experiments, ex vivo incubation (18 hours) of rat aortic rings with

the organic sub-fraction of ALE enhanced the NO-mediated vasodilator

response to acetylcholine, indicating that the upregulated eNOS

remained functional. Caffeoylquinic acids and flavonoids are two

major groups of constituents of ALE. Interestingly, the flavonoids

luteolin and cynaroside increased eNOS promoter activity and eNOS

mRNA expression, whereas the caffeoylquinic acids cynarin and

chlorogenic acid were without effect. Thus, in addition to the lipid-

lowering and anti-oxidant properties of artichoke, an increase in

eNOS gene transcription may also contribute to its beneficial

cardiovascular profile. Artichoke flavonoids are likely to represent

the active ingredients mediating eNOS upregulation.

---

Anti-hyperlipidemic sesquiterpenes and new sesquiterpene glycosides

from the leaves of artichoke (Cynara scolymus L.): structure

requirement and mode of action.

Shimoda H, Ninomiya K, Nishida N, Yoshino T, Morikawa T, Matsuda H,

Yoshikawa M.

Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-

8412, Japan.

Bioorg Med Chem Lett. 2003 Jan 20;13(2):223-8.

The methanolic extract from the leaves of artichoke (Cynara scolymus

L.) was found to suppress serum triglyceride elevation in olive oil-

loaded mice. Through bioassay-guided separation, sesquiterpenes

(cynaropicrin, aguerin B, and grosheimin) were isolated as the active

components together with new sesquiterpene glycosides

(cynarascolosides A, B, and C). The oxygen functional groups at the 3-

and 8-positions and exo-methylene moiety in alpha-methylene-gamma-

butyrolactone ring were found to be essential for the anti-

hyperlipidemic activity of guaiane-type sesquiterpene. In addition,

inhibition of gastric emptying was shown to be partly involved in

anti-hyperlipidemic activity.

---

Artichoke leaf extract for treating hypercholesterolaemia.

Pittler MH, CO, Ernst E.

Department of Complementary Medicine, University of Exeter, 25

Park Road, Exeter, Devon, UK, EX2 4NT. M.H.Pittler@...

Cochrane Database Syst Rev. 2002;(3):CD003335.

BACKGROUND: Hypercholesterolaemia is directly associated with an

increased risk for coronary heart disease and other sequelae of

atherosclerosis. Artichoke leaf extract (ALE), which is available as

an over-the-counter remedy, has been implicated in lowering

cholesterol levels. Whether ALE is truly efficacious for this

indication, however, is still a matter of debate. OBJECTIVES: To

assess the evidence of ALE versus placebo or reference medication for

treating hypercholesterolaemia defined as mean total cholesterol

levels of at least 5.17 mmol/L (200 mg /dL). SEARCH STRATEGY: We

searched MEDLINE, Embase, Amed, Cinahl, CISCOM and the Cochrane

Controlled Trial Register. All databases were searched from their

respective inception until June 2001. Reference lists of articles

were also searched for relevant material. Manufacturers of

preparations containing artichoke extract and experts on the subject

were contacted and asked to contribute published and unpublished

material. SELECTION CRITERIA: Randomized controlled trials of ALE

mono-preparations compared with placebo or reference medication for

patients with hypercholesterolaemia were included. Trials assessing

ALE as one of several active components in a combination preparation

or as a part of a combination treatment were excluded. DATA

COLLECTION AND ANALYSIS: Data were extracted systematically and

methodological quality was evaluated using a standard scoring system.

The screening of studies, selection, data extraction and the

assessment of methodological quality were performed independently by

two reviewers. Disagreements in the evaluation of individual trials

were resolved through discussion. MAIN RESULTS: Two randomised trials

including 167 participants met all inclusion criteria. In one trial

ALE reduced total cholesterol levels from 7.74 mmol/l to 6.31 mmol/l

after 42 +/- 3 days of treatment whereas the placebo reduced

cholesterol from 7.69 mmol/l to 7.03 mmol/l (p=0.00001). Another

trial did state that ALE significantly (p<0.05) reduced blood

cholesterol compared with placebo in a sub-group of patients with

baseline total cholesterol levels of more than 230 mg/dl. Trial

reports and post-marketing surveillance studies indicate mild,

transient and infrequent adverse events. REVIEWER'S CONCLUSIONS: Few

data from rigorous clinical trials assessing ALE for treating

hypercholesterolaemia exist. Beneficial effects are reported, the

evidence however is not compelling. The limited data on safety

suggest only mild, transient and infrequent adverse events with the

short term use of ALE. More rigorous clinical trials assessing larger

patient samples over longer intervention periods are needed to

establish whether ALE is an effective and safe treatment option for

patients with hypercholesterolaemia.

---

Inhibition of cholesterol biosynthesis in HepG2 cells by artichoke

extracts is reinforced by glucosidase pretreatment.

Gebhardt R.

Institut fur Biochemie, Universitatsklinikum Leipzig, 04103 Leipzig,

Germany.

Phytother Res. 2002 Jun;16(4):368-72.

High-dose aqueous extracts from artichoke leaves were found to

inhibit cholesterol biosynthesis from (14)C-acetate rather moderately

in HepG2 cells in contrast to primary cultured rat hepatocytes in

which the inhibition was stronger. Preincubation of the extracts with

several glycohydrolases revealed that pretreatment with beta-

glucosidase considerably reinforced the inhibition. A significant

reduction of acetate incorporation was found above extract

concentrations of 0.01 mg/mL and at 0.2 mg/mL almost 60% inhibition

was observed. Cytotoxic effects detected by the MTT-assay were

restricted to higher concentrations of the extracts with and without

beta-glucosidase pretreatment. Since cynaroside represents a major

glucoside in artichoke extracts, both cynaroside and its aglycone

luteolin were tested. It could be demonstrated that cynaroside is

indeed one of the targets of beta-glucosidase and that the liberated

luteolin is responsible for the inhibitory effect. Direct

measurements of beta-glucosidase activity in rat hepatocytes and

HepG2 cells revealed that endogenous enzyme activity in hepatocytes

may be sufficient to convert cynaroside to its aglycone, while in

HepG2 cells this may not be the case. These findings emphasize the

importance of beta-glucosidase-dependent liberation of luteolin for

the ability of artichoke extracts to inhibit hepatic cholesterol

biosynthesis.

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Anticholestatic activity of flavonoids from artichoke (Cynara

scolymus L.) and of their metabolites.

Gebhardt R.

Institut fur Biochemie, Universitatsklinikum Leipzig, Germany.

rgebhardt@...

Med Sci Monit. 2001 May;7 Suppl 1:316-20.

It is well known that water-soluble extracts of artichoke (Cynara

scolymus L.) leaves exert choleresis. When studying this effect in

vitro using primary cultured rat hepatocytes and cholephilic

fluorescent compounds, it was noticed that the artichoke leaf

extracts not only stimulated biliary secretion, but that they also

reestablished it when secretion was inhibited by addition of

taurolithocholate to the culture medium. Furthermore,

taurolithocholate-induced bizarre bile canalicular membrane

distortions detectable by electron microscopy could be prevented by

artichoke leaf extracts in a dose-dependent manner when added

simultaneously with the bile acid. These effects were exerted by the

flavonol luteolin and, to a lesser extent, by luteolin-7-O-glucoside,

while chlorogenic acid and 1.5-dicaffeoyl quinic acid were almost

ineffective. Surprisingly, metabolites produced by the cultured

hepatocytes were able to stimulate biliary secretion substantially as

well as prevent canalicular membrane deformation. These results

demonstrate that artichoke leaf extracts exert a potent

anticholestatic action at least in the case of taurolithocholate-

induced cholestasis. Flavonoids and their metabolites may contribute

significantly to this effect.

AGED GARLIC EXTRACT

Cholesterol-lowering effect of garlic extracts and organosulfur

compounds: human and animal studies.

Yeh YY, Liu L.

Department of Nutrition, The Pennsylvania State University,

University Park, PA 16802, USA. yyy1@...

J Nutr. 2001 Mar;131(3s):989S-93S.

The medicinal use of garlic dates back thousands of years, but there

was little scientific support of its therapeutic and pharmacologic

properties until recently. In the past decade, the cancer-protective

effects of garlic have been well established by epidemiologic studies

and animal experiments. However, the cardiovascular-protective

properties of garlic are less well understood. In particular, despite

the reported hypocholesterolemic effect of garlic, the mechanism of

the effect is unclear. In a recent randomized, double-blind, placebo-

controlled intervention study, we showed that aged garlic extract

(AGE) supplementation was effective in lowering plasma concentration

of total cholesterol by 7% and LDL cholesterol by 10% in

hypercholesterolemic men compared with subjects consuming a placebo.

Supplementation of AGE in animal diets similarly reduced plasma

concentrations of total cholesterol and triacylglycerol by 15 and

30%, respectively. In subsequent experiments using cultured rat

hepatocytes, we found 44--87% inhibition of cholesterol synthesis by

the water-extractable fraction (WEF), methanol-extractable fraction

(MEF) and petroleum ether-extractable fraction (PEF) of fresh garlic,

and Kyolic (liquid form of AGE). These observations suggested that

hydrophilic and hydrophobic compounds of garlic are inhibitory to

cholesterol synthesis. Because S-allylcysteine (SAC) alone was less

potent than Kyolic, which contains SAC and other sulfur compounds, a

maximal inhibition appears to require a concerted action of multiple

compounds of garlic. In a series of experiments, we further

characterized the inhibitory potency of individual water-soluble and

lipid-soluble compounds of garlic. Among water-soluble compounds,

SAC, S-ethylcysteine (SEC), and S-propylcysteine (SPC) inhibited

cholesterol synthesis by 40--60% compared with 20--35% by gamma-

glutamyl-S-allylcysteine (GSAC), gamma-glutamyl-S-methylcysteine

(GSMC) and gamma-glutamyl-S-propylcysteine (GSPC). Lipid-soluble

sulfur compounds (i.e., diallyl sulfide, diallyl disulfide, diallyl

trisulfide, dipropyl sulfide and dipropyl trisulfide) at low

concentrations (0.05--0.5 mol/L) slightly (10--15%) inhibited

cholesterol synthesis but became highly cytotoxic at high

concentrations (1.0--4.0 mol/L). All water-soluble compounds, except

S-allylmercaptocysteine, were not cytotoxic, judging from the release

of cellular lactate dehydrogenase into the culture medium. Taken

together, the results of our studies indicate that the cholesterol-

lowering effects of garlic extract, such as AGE, stem in part from

inhibition of hepatic cholesterol synthesis by water-soluble sulfur

compounds, especially SAC.

---

A double-blind crossover study in moderately hypercholesterolemic men

that compared the effect of aged garlic extract and placebo

administration on blood lipids.

Steiner M; Khan AH; Holbert D; Lin RI

Memorial Hospital of Rhode Island, Pawtucket, USA

Steiner@...

Am J Clin Nutr (United States) Dec 1996, 64 (6) p866-70

A double-blind crossover study comparing the effect of aged garlic

extract with a placebo on blood lipids was performed in a group of 41

moderately hypercholesterolemic men [cholesterol concentrations 5.7-

7.5 mmol/L (220-290 mg/dL)]. After a 4-wk baseline period, during

which the subjects were advised to adhere to a National Cholesterol

Education Program Step I diet, they were started on 7.2 g aged garlic

extract per day or an equivalent amount of placebo as a dietary

supplement for a period of 6 mo, then switched to the other

supplement for an additional 4 mo. Blood lipids, blood counts,

thyroid and liver function measures, body weight, and blood pressure

were followed over the entire study period. The major findings were a

maximal reduction in total serum cholesterol of 6.1% or 7.0% in

comparison with the average concentration during the placebo

administration or baseline evaluation period, respectively. Low-

density-lipoprotein cholesterol was also decreased by aged garlic

extract, 4% when compared with average baseline values and 4.6% in

comparison with placebo period concentrations. In addition, there was

a 5.5% decrease in systolic blood pressure and a modest reduction of

diastolic blood pressure in response to aged garlic extract. We

conclude that dietary supplementation with aged garlic extract has

beneficial effects on the lipid profile and blood pressure of

moderately hypercholesterolemic subjects.

---

Changes in platelet function and susceptibility of lipoproteins to

oxidation associated with administration of aged garlic extract

Steiner M.; Lin R.S.

Dr. M. Steiner, Division of Hematology/Oncology, East Carolina

University, School of Medicine, Greenville, NC 27858-4354 United

States

Journal of Cardiovascular Pharmacology (United States), 1998, 31/6

(904-908)

Garlic and some of its organosulfur components have been found to be

potent inhibitors of platelet aggregation in vitro. Demonstration of

their efficacy in vivo, however, especially when administered over

extended periods, is sparse. We recently performed a 10-month study

comparing the effect of aged garlic extract (AGE) with placebo on the

lipid profiles of moderately hypercholesterolemic men. In the course

of the intervention trial, we examined platelet functions and

susceptibility of lipoproteins to oxidation in a subgroup of this

study population. Study subjects supplemented with 7.2 AGE per day

showed a significant reduction of epinephrine- and, to a lesser

degree, collagen-induced platelet aggregation but failed to

demonstrate an inhibition of adenosine diphosphate (ADP)-induced

aggregation. Platelet adhesion to fibrinogen, measured in a laminar

flow chamber at moderately high shear rate, was reduced by similar30%

in subjects taking AGE compared with placebo supplement. A trend

toward decreased susceptibility of lipoproteins to oxidation also was

noted during AGE administration compared with the placebo period. We

conclude that the beneficial effect of garlic preparations on lipids

and blood pressure extends also to platelet function, thus providing

a wider potential protection of the cardiovascular system.

CURCUMIN

Hypolipidemic action of curcumin, the active principle of turmeric

(Curcuma longa) in streptozotocin induced diabetic rats

Babu PS; Srinivasan K

Department of Biochemistry and Nutrition, Central Food Technological

Research Institute, Mysore, India.

Molecular and Cellular Biochemistry (Netherlands), 1997, 166/1-2 (169-

175)

Streptozotocin-induced diabetic rats were maintained on 0.5% curcumin

containing diet for 8 weeks. Blood cholesterol was lowered

significantly by dietary curcumin in these diabetic animals.

Cholesterol decrease was exclusively from LDL-VLDL fraction.

Significant decrease in blood triglyceride and phospholipids was also

brought about by dietary curcumin in diabetic rats. In a parallel

study, wherein diabetic animals were maintained on a high cholesterol

diet, the extents of hypercholesterolemia and phospholipidemia were

still higher compared to those maintained on control diet. Curcumin

exhibited lowering of cholesterol and phospholipid in these animals

also. Liver cholesterol, triglyceride and phospholipid contents were

emin showed a distinct tendency to counter these changes in lipid

fractions of liver. This effect of curcumin was also seen in diabetic

animals maintained on high cholesterol diet. Dietary curcumin also

showed significant countering of renal cholesterol and triglycerides

elevated in diabetic rats. In order to understand the mechanism of

hypocholesterolemic action of dietary curcumin, activities of hepatic

cholesterol-7a-hydroxylase and HMG CoA reductase were measured.

Hepatic cholesterol-7a-hydroxylase activity was markedly higher in

curcumin fed diabetic animals suggesting a higher rate of cholesterol

catabolism.

---

The effect of spices on cholesterol 7 alpha-hydroxylase activity and

on serum and hepatic cholesterol levels in the rat.

Srinivasan K; Sambaiah K

Department of Food Chemistry, Central Food Technological Research

Institute, Mysore, India.

Int J Vitam Nutr Res (Switzerland) 1991, 61 (4) p364-9

The effect of feeding curcumin, capsaicin, ginger, mustard, black

pepper and cumin on cholesterol and bile acid metabolism was studied

in rats. The activity of hepatic cholesterol-7 alpha-hydroxylase, the

rate-limiting enzyme of bile acid biosynthesis, was significantly

elevated in curcumin (turmeric), capsaicin (red pepper), ginger and

mustard treated animals. The enzyme activity was comparable to

controls in black pepper and cumin fed rats. Serum and liver

microsomal cholesterol contents were significantly higher in the

curcumin and capsaicin treated animals. Thus, this study has

suggested that the spices--turmeric, red pepper, ginger and mustard

can stimulate the conversion of cholesterol to bile acids, an

important pathway of elimination of cholesterol from the body.

However, simultaneous stimulation of cholesterol synthesis by the

spice principles--curcumin and capsaicin suggests that there may not

be any significant contribution of stimulation of bile acid

biosynthesis to the hypocholesterolemic action of these spices, and

the latter action may solely be due to interference with exogenous

cholesterol absorption.

---

Influence of capsaicin, eugenol, curcumin and ferulic acid on sucrose-

induced hypertriglyceridemia in rats

Srinivasan M.R.; Satyanarayana M.N.

Biochemistry Section, Department of Food Chemistry, Central Food

Technological Research Institute, Mysore-570 013 India

Nutr. Rep. Int. (USA), 1988, 38/3 (571-581)

The spice active principles, capsaicin, eugenol curcumin and 'ferulic

acid' a common plant constituent were found to counter many of the

metabolic changes caused by a high sucrose diet fed to rats. The

compounds tested at high and low levels were mostly found to lower or

tend to lower liver weight, liver triglycerides, free fatty acids,

phospholipids, serum total, VLDL+LDL and HDL triglycerides, VLDL+LDL

cholesterol, free fatty acids and also elevate serum total and HDL

cholesterol.

GUGULIPID

Hypolipidemic effects of synthetic gugulsterones in normal rats and

assessment of its long-term toxicity at cellular levels in various

organs.

Far SR; Master HE; Billimoria FR; Sane RT

Dept. of Biochemistry, L.T.M. Medical College, Sion, Bombay.

Indian J Med Sci (India) Mar 1996, 50 (3) p63-7

Synthetic gugulsterones when administered to rats for a period of 3

weeks in dose of 5.0 mg/kg body weight/day caused a reduction in

levels of total cholesterol by 30%, LDL-chol. by 40%, Tg by 40%. VLDL-

chol. by 40% and HDL-chol. by 35%. The drug when administered to rats

for a period of 16 weeks with increasing dose upto 1150 mg/kg body

weight/day, reduced VLDL-chol. and Tg. by 55% and 50% respectively (P

< 0.001) and LDL-chol by 33% (P < 0.05), whereas HDL-chol. was

increased by 25% (P < 0.001). Histopathological studies on liver,

spleen, intestine, lung, kidney, stomach and adrenal gland revealed

drug related changes in a few animals upon exposure to high dose of

the drug.

---

Recent trends in hyperlipoproteinemias and its pharmacotherapy

Ghatak A.; Asthana O.P.

Division of Clinical, Experimental Medicine, Central Drug Research

Institute, P.O. Box No. 173,Lucknow - 226 001 India

Indian Journal of Pharmacology (India) 1995, 27/1 (14-29)

Hyperlipoproteinemias cause atherosclerosis which is a major cause of

death in the developed world and is also now becoming a major cause

of morbidity and mortality in India, especially with changing

lifestyles and increasing stress and food habits shifting towards

the 'fast food' era. If is extremely important to understand the risk

factors, the criteria for starting treatment, the efficacy and safety

profile of drugs for hyperlipoproteinemia and the drugs which are

available for pharmacotherapy especially in the Indian perspective.

The significant contributions of Central Drug Research Institute,

Lucknow in developing potent lipid lowering drugs like Gugulipid an

already marketed product and a new synthetic drug coded as compound

80/574 in the early phase of clinical trials have been specially

discussed in this article. At present it is recommended that for mild

to moderate hyperlipoproteinemia Gugulipid would be an extremely cost

effective indigenous choice and with the further development of the

new CDRI compound 80/574 even moderate to severe hyperlipoproteinemia

would be manageable. The other alternatives like Gemfibrozil though

highly effective for moderate to severe hyperlipoproteinemia are

extremely expensive and have other side effects and only very few can

afford to take it on long term basis in India.

---

Hypolipidemic and antioxidant effects of Commiphora mukul as an

adjunct to dietary therapy in patients with hypercholesterolemia

Singh RB; Niaz MA; Ghosh S

Heart Research Laboratory, Medical Hospital and Research Centre,

Moradabad, India.

Cardiovasc Drugs Ther (United States) Aug 1994, 8 (4) p659-64

The effects of the administration of 50 mg of guggulipid or placebo

capsules twice daily for 24 weeks were compared as adjuncts to a

fruit- and vegetable-enriched prudent diet in the management of 61

patients with hypercholesterolemia (31 in the guggulipid group and 30

in the placebo group) in a randomized, double-blind fashion.

Guggulipid decreased the total cholesterol level by 11.7%, the low

density lipoprotein cholesterol (LDL) by 12.5%, triglycerides by

12.0%, and the total cholesterol/high density lipoprotein (HDL)

cholesterol ratio by 11.1% from the postdiet levels, whereas the

levels were unchanged in the placebo group. The HDL cholesterol level

showed no changes in the two groups. The lipid peroxides, indicating

oxidative stress, declined 33.3% in the guggulipid group without any

decrease in the placebo group. The compliance of patients was greater

than 96%. The combined effect of diet and guggulipid at 36 weeks was

as great as the reported lipid-lowering effect of modern drugs. After

a washout period of another 12 weeks, changes in blood lipoproteins

were reversed in the guggulipid group without such changes in the

placebo group. Side effects of guggulipid were headache, mild nausea,

eructation, and hiccup in a few patients.

--

Clinical trials with gugulipid. A new hypolipidaemic agent

Nityanand S; Srivastava JS; Asthana OP

J Assoc Physicians India (India) May 1989, 37 (5) p323-8

Multicentric clinical trials of the efficacy of gugulipid conducted

at Bombay, Bangalore, Delhi, Jaipur, Lucknow, Nagpur and Varanasi

have been reported. Two hundred and five patients completed 12 week

open trial with gugulipid in a dose of 500 mg tds after 8 week diet

and placebo therapy. One patient showed gastrointestinal symptoms

which did not necessitate withdrawal of the drug. A significant

lowering of serum cholesterol (av. 23.6%) and serum triglycerides

(av. 22.6%) was observed in 70-80% patients Double-blind, crossover

study was completed in 125 patients with gugulipid therapy and in 108

patients with clofibrate therapy. Two patients had flu-like syndrome

with clofibrate and opted out from the study. With gugulipid the

average fall in serum cholesterol and triglycerides was 11 and 16.8%

respectively and with clofibrate 10 and 21.6% respectively. The lipid

lowering effect of both drugs became evident 3-4 week after starting

the drug and had no relationship with age, sex, and concomitant drug

intake. Hypercholesterolaemic patients responded better to gugulipid

therapy than hypertriglyceridaemic patients who responded better to

clofibrate therapy. In mixed hyperlipidaemic patients response to

both drugs was comparable. HDL- cholesterol was increased in 60%

cases who responded to gugulipid therapy. Clofibrate had no effect on

HDL- cholesterol. A significant decrease in LDL-cholesterol was

observed in the responder group to both drugs.

FLAX SEED

Whole flaxseed consumption lowers serum LDL- cholesterol and

lipoprotein(a) concentrations in postmenopausal women

Arjmandi B.H.; Khan D.A.; Juma S.; Drum M.L.; Venkatesh S.; Sohn E.;

Wei L.; Derman R.

Dr. B.H. Arjmandi, Department of Nutritional Sciences, 425 Human

Environmental Sciences, Oklahoma State University, Stillwater, OK

74078-6141 United States

Nutrition Research (United States), 1998, 18/7 (1203-1214)

We conducted a double-blind cross-over study to compare the effects

of whole flaxseed and sunflower seed, as part of the daily diet, on

the lipid profile of postmenopausal women. During two 6-wk periods,

thirty-eight mild, moderate, or severely (5.85-9.05 mmol/L)

hypercholesterolemic postmenopausal women were randomly assigned to

one of the two regimens: flaxseed or sunflower seed. The subjects

were provided with 38 g of either treatment in the forms of breads

and muffins. The first treatment period lasted six weeks and was

followed by a two-wk washout phase. After the washout phase, subjects

switched regimens and treatments continued for another 6 weeks. Blood

samples were collected at baseline, 6, 8, and 14th wk of the study

periods. Significant (p<0.01) reductions in total cholesterol were

observed for both treatments (6.9 and 5.5% for flaxseed and sunflower

seed, respectively). However only flaxseed regimen was able to

significantly (p<0.001) lower LDL- cholesterol (14.7%). Serum HDL-

cholesterol and triglyceride concentrations were unaffected by either

of the treatments. Most interestingly, lipoprotein(a) [Lp(a) ], a

strong predictor of cardiovascular disease, concentrations were

significantly (p<0.05) lowered by the flaxseed treatment (7.4%

compared to baseline values). Regression analyses showed the

strongest association between age and both total and LDL- cholesterol

concentrations. Among the dietary variables, total and soluble fiber

intakes were negatively correlated with serum total and LDL-

cholesterol concentrations. The cholesterol lowering effects of

flaxseed and sunflower seed may be due to the activity of single or

multiple components, including alpha-linolenic or linoleic acids,

total and soluble fiber , and non-protein constituents present in

these seeds.

>

> > In order of importance:

> >

> > 1. Avoid ingesting all deadly trans-fats, isolated fructose and

high-

> > insulinic carbohydrates.

> >

> > 2. Correct hormonal imbalance with bio-identical hormone therapy.

> >

> > 3. Ingest soluble fiber, pharmaceutical-grade fish oil, mixed

natural

> > vitamin E, policosanol, artichoke leaf extract, aged garlic

extract,

> > curcumin, gugulipid, green tea, flushful niacin, flax seed oil,

soy.

> > The last three should be taken with caution.

> >

> > Logan

> >

[Guest guest]

Several of these studies are several years old. The field of nutrition

changes rapidly and we can't rely on anything but the most recent

information.

Where did you find these? (We rely on only mainstream studies from the most

esteemed, peer reviewed scientific journals such as found on Pubmed).

----------

From: " loganruns73 " <loganruns73@...>

Reply-

Date: Fri, 30 Jul 2004 12:57:51 -0000

Subject: [ ] Re: lowering total cholesterol

I don't have time to post abstracts for every treatment approach, so

I'll post some for the lesser-known.

Logan

[Guest guest]

--- In , " Jeff Novick " <jnovick@p...

> recommended. If

> I left CSPI out and posted the newer studies myself (which I did for

> policosanol) it doesn't make it more meaningful, but if you would

> prefer, I can do that. Then, we are still in the same place......

All right, fair enough. You obviously keep more up to date with

recent research than laymen like me.

> Personally, I am surprised that someone who would insist on such

> " quality " and " integrity " and be so quick to point out

the " misguided "

> shortcomings of one organization, yet fail to see the " glaring "

> shortcomings of the data they use to support their position.

That was only relative to just one or two of the recent studies you

posted. But I'll take your word for it there are more recent

contradictory or inconclusive studies on the substances in question.

> Removing beef tallow/palm/coconut was not misguided. The industries

> (not CSPI's) response to use hydrogenated oils (and the resulting

trans

> fat) is not CSPIs fault nor was it their recommendation. I also

I don't have time to prove in detail how it was indeed misguided even

though millions of years of human evolution is on my side. A good

place to start is by reading " The Lipid Hypothesis " section at

http://www.nursingceu.com/NCEU/courses/diet/

Propaganda has to be much more sophisticated and relentless to work

succesfully in a democracy as opposed to a dictatorship. So the fact

is that CSPI did mount an enormous propaganda campaign in the late

80's to demonize and remove tropical oils and saturated fats from all

junk and fast food, ignoring (whether good or a lack of) science and

economic conspiracy. They should be guilty of criminal association

especially due to the enormous influence over " public opinion " they

wield. CSPI may not be the " right arm " like the FDA is, but they

certainly do act as the " left arm " . Like many other organizations,

they're also complicit in helping Americans become overweight/obese.

> don't see them promoting the same old agenda as they just are part

> of the movement that just succeded in having trans fat labeling

> required and trans fat removed from packaged foods and are now

> working on restaurants.

As per the typical boondoggle: propagandize an original " problem " so

you can then wind up proposing " solutions " to fix the

original " problem " . And in the interim, the new and unexpected

problem always winds up being worse than the original " problem " .

What revealed danger in 20-30 years from now will there be from

spearheading this new movement to postmodern, tasteless, trans-fat

free canola oil? Prostate cancer?

> I still like to see some recent good data on any of the questionable

> supplements you mentioned that I responded to.

I'll leave that up to you to research, if you really care. The

studies on the other substances seem robust enough to warrant a lack

of promoting statin therapy. :-)

Logan

[Guest guest]

> Vit E, (100-200 d alpha, 100-200 d-gamma, 100 IU tocotrienol).

> Mixed tocophorols are better however, if someone is on a statin, I

> wouldnt recommend this. There may be some benefit in reducing risk

> for

Why not?

> Vit C (500-100 in ester form) I disagree. I have concerns about

> excess vit c. I can post some data later, but we get way more than

> we need from a healthy diet.

Ester-C is oxidized Vitamin C. No one should be ingesting that! I'm

sure your studies will be using synthetic, isolated Vitamin C but

it'll be interesting nonetheless if there appears to be an upper

limit for such a form. I've never feel quite psychologically

comfortable taking " low dose " Vitamin C from whole food, even if with

superior bio-availability and bio-utilization. How do you address

the issue of mammals producing truly humongous quantities of Vitamin

C internally that we have no hell of any chance to ingest by mouth?

> Chromium (50 mcg) I agree In diabetics, would even up it to 200

> mcg with some magnesium and selenium.

Is there a co-dependence of magnesium and selenium with chromimum?

> Co Q 10 : (100mg) If on a statin, I agree. Otherwise, debatable

How much exactly if on statins? Is there a fixed ratio of CoQ10

amount to statin amount? Could 100mg be too low? There's sizes up

to 400mg now.

Logan

[Guest guest]

Hi Jeff. Would you please post your concerns about " excessive " Vit C

supplementation?

TIA

>

> >> what do you think of Walford's list of supplements pg 165-167, 120

> yo?

>

> I will list the nutrient, (Dr Walfords Recommendations in paranthesis)

> and my comments.

>

> First, I agree with his general recommendation of not supplementing more

> than 50-100% of the RDA for most nutrients.

>

> Vit A, (None), I agree. Can increase risk for Osteo and fractures.

> In addition, the RDA was lowered since the publication of the book and

> an UL (upper limit) was set for the first time of 10,000

>

> Vit D, (800 - 1000 including amt from sun/dairy), I agree. In some

> areas of the country/world, especially in the Northern climates where

> there is less sun exposure and along with everyones fear of the sun and

> constant 24 hr use of sunscreen, I agree.

>

> Vit E, (100-200 d alpha, 100-200 d-gamma, 100 IU tocotrienol). Mixed

> tocophorols are better however, if someone is on a statin, I wouldnt

> recommend this. There may be some benefit in reducing risk for

> Alzheimers, Macular Degeneration and certain cancers. And for most

> people, eating the typical way, Vit E may be difficult to get. So, I

> think this is more individual based on personal situation. I wouldnt

> give a generic recommendation

>

> Vit K; (400 mcg including food sources). I agree, but for most of us,

> especially CR-ON and other healthy vegetable eaters, this should be no

> problem getting it from food

>

> Vit C (500-100 in ester form) I disagree. I have concerns about excess

> vit c. I can post some data later, but we get way more than we need

> from a healthy diet.

>

> B1 (RDA) I agree

> B2 (RDA) I agree

>

> Niacin (100-300mg). I disagree. I agree with supplementing nicain

> where appropriate for lowering LDL and raising HDL but the amount needed

> is much more than this. So, I am not sure of the proposed benefit of

> this smaller amount.

>

> Folate (800) I agree but i would count in food sources towards the

> total. On a healthy diet, its easy to even get the 800. A typical diet

> is tough to get 200. So, shoot for 800.

>

> B6 (50mg) I dont see the need except in certain situations so this

> would be individual. Along with folate and B12 may be important for

> elevated homocysteine levels.

>

> B12 (200) agree. might even recommend more as absorbtion is very low

> and may go lower as people age. 500-1000 mcg is safe on a daily basis.

>

>

> Calcium (enough to get to RDA) I agree but also limit intake of salt,

> and get some weight bearing exercise.

>

> Magnesium (500 mg) i would agree with 400-500.

>

> Selenium (200) RDAs were lowered from 70 - 55 at the same time Vit A

> was lowered a year or two ago. With the change I would recommend

> 50-100 for most. And, as he says, eating a brazil nut or 2 a day can

> easily do it.

>

> Iron (none) I agree except in rare situations on a as needed basis

>

> zinc (no more than 30 mg) I agree

>

> Manganese (RDA ) i agree

>

> Chromium (50 mcg) I agree In diabetics, would even up it to 200 mcg

> with some magnesium and selenium.

>

> Alpha Lipoic Acid (50). For Peripheral Neurpoathy, around 600-1000 can

> help, so i would agree but with much more. Than the new formula from Dr

> Ames in which i think he recommends 100 (or 200?) which if someone

> wanted to take, I am OK with.

>

> Acetyl l carnitine (500) same as comment for Dr Ames formula

>

> Bio-flavonoids (500) I dont see the need in a healthy diet

>

> Co Q 10 : (100mg) If on a statin, I agree. Otherwise, debatable

>

> SAMe (200-400) Not in general

>

> Omega 3s (500-700 mg mixed EPA/DHA) I disagree, first get it from food.

>

> I think I got them all. If I missed one, let me know. I may add some

> more comments when I have some time over the weekend.

>

> Regards

> Jeff