Chapter 49


Low Blood Levels Of Carotene In
Patients With Coronary Atherosclerosis

Riemersma et al (1991) investigated the relationship between the risk of angina pectoris and plasma concentrations of various vitamins in a population case-control study of 110 cases of angina.

Low plasma concentrations of carotene were associated with an increased risk of angina. Interestingly, there was no significant association with plasma concentrations of vitamin A. This may help explain the conflicting reports of of the relationship when blood levels of vitamin A without carotene levels are measured in clinical studies.

The reserchers concluded that populations with a high incidence of coronary heart disease may benefit from eating diets rich in fruits and vegetables containing carotene such as carrots and green-leaf vegetables.

Low Carotene/Lipoprotein Blood Levels In
Patients With Coronary Artery Disease

Croft et al (1992) compared 20 men with angiogram-proven coronary disease with 25 controls who had no clinical evidence of arterial disease. Low-density lipoprotein-cholesterol, total triglycerides and low-density lipoprotein fatty acid composition did not differ significantly between the groups. Low-density lipoprotein beta-carotene, however, was found to be significantly lower in patients with coronary atherosclerosis.

Low Body Adipose Tissue Carotene
Levels In Patients With Myocardial Infarction

Kardinaal et al (1993) reported the results of a European multicentre, case-control study of beta-carotene concentrations which were measured in adipose-tissue samples collected in 1991-92 from 683 people with acute myocardial infarction and 727 controls.

It was found that beta-carotene concentration in adipose-tissue was significantly lower in cases of myocardial infarction than in the controls. Increased risk was mainly confined to current smokers. It was concluded by the researchers that high beta-carotene concentrations within the normal range significantly reduce the risk of a first myocardial infarction. It was also suggested that consumption of carotene-rich foods, such as carrots and the green-leaf vegetables, may reduce the risk of myocardial infarction.


Aflatoxin, Ochratoxin, And T-2 Toxin Reduce
Blood Levels Of Carotenoids (Vitamin A) (4 Studies)

1. Osborne et al. (1982) induced aflatoxicosis, ochratoxicosis, and T-2 toxicosis by feeding diets containing graded concentrations of each toxin to broiler chicks from a hatching unit at 3 weeks of age. Each of the three toxins caused a reduction in the blood levels of carotenoids.

2. In their experiments to induce experimental aflatoxicosis in young Japanese quail, Chang and Hamilton (1982) found that aflatoxin caused reduced blood levels of carotene.

3. Doerr et al. (1983) found that aflatoxin produced low blood levels of carotenoids in dosed chickens.

4. Liu and Zhou (1989) found that aflatoxin reduced the blood and liver levels of vitamin A in mice.


Low Levels Of Blood Carotenoids Associated
With Increased Risk Of Second Heart Attacks

Street et al (1994) examined the association between levels of vitamins and myocardial infarction using serum specimens collected 7 to 14 years before the onset of myocardial infarction. Cases and control subjects were selected from 25,802 persons who had donated blood to a serum bank in 1974. Cases were comprised of 123 persons with a subsequent first diagnosis of myocardial infarction who ranged from 23 to 58 years of age in 1974 and who had their first diagnosis of myocardial infarction during 1981 to 1988.

The researchers found that low serum levels of carotenoids were associated with an increased risk of subsequent myocardial infarction among smokers.


Deficiency Of Vitamin A Increases Toxicity 
And Carcinogenicity Of Aflatoxin (2 Studies)

1. Nikov and Parzian (1985) found that vitamin A deficiency resulted in the formation of highly reactive metabolites of aflatoxin. This finding indicated that increased toxicity and carcinogenicity of the mycotoxin was caused by the vitamin deficiency.

2. Hamilton (1977) documented that a deficiency of vitamin A makes test animals more sensitive to the effects of aflatoxin. Such a deficiency increases the relative toxicity of aflatoxin.


Carotene Reduces Risk
Of Coronary Heart Disease

Rimm et al (1993) reported the results of their study of the relationship of various vitamins and the risk of coronary heart disease in men. In 1986, 39,910 U.S. male health professionals 40 to 75 years of age who were free of diagnosed coronary heart disease, diabetes, and hypercholesterolemia, completed detailed dietary questionnaires which assessed their usual intake of carotene in addition to other nutrients. During four years of follow-up, the authors documented 667 cases of coronary artery disease.

While carotene intake was not associated with decreased risk in non-smokers, it did reduce the risk in smokers.

Vitamin A Protects Against Coronary Disease

Todd et al (1995) investigated vitamin (C,E and carotene) intake as assessed by a food frequency questionnaire completed by 10,359 middle-aged men and women participating in the Scottish Heart Health Study. The researchers found that vitamin A had a protective effect against coronary artery disease in men.

Higher Blood Carotenoid Levels Associated
With Decreased Coronary Heart Disease.

Morris et al (1994) (Lipid Research Clinics Coronary Primary Prevention Trial and Follow-up Study) studied the relationship between total serum carotenoid levels and the risk of subsequent coronary heart disease events. They found that persons with higher serum carotenoid levels had a decreased risk of developing coronary heart disease.

Dietary Carotene
Protects Against Heart Attacks

Knekt et al (1994) studied the relationship of dietary carotene and subsequent coronary mortality in a cohort of 5,133 Finnish men and women aged 30-69 years who were initially free from heart disease. Food consumption was estimated by the dietary history method covering the total habitual diet during the previous year. Altogether, 244 new fatal coronary heart disease cases occurred during a mean follow-up of 14 years beginning in 1966-1972. It was observed that both men and women who had a high dietary carotene intake derived from fruits and vegetables had significantly decreased risk of death from heart attacks.

Higher Vitamin A Intake
Associated With Higher Levels Of
High Density Lipoprotein ("Good Cholesterol")

Lamon-Fava et al (1994) measured plasma lipid and apolipoprotein (apo) A-I and B concentrations and habitual dietary intakes in 306 free-living elderly individuals (119 men and 187 women, age range 60-100 y). Higher vitamin A intake was associated with higher plasma concentrations of high-density lipoprotein cholesterol and apo A-I. The researchers concluded that both dietary and plasma concentrations of vitamin A are important determinants of more healthy blood lipid concentrations in the elderly.

Carotene Does Not Have An Adverse Effect On
Triglycerides Or Cholesterol In Normal Humans

A number of studies have indicated that chronic oral administration of retinol and other retinoids causes elevation of plasma triglyceride concentrations. These reports prompted Nierenberg et al (1991) to investigate the effects of chronic oral administration of beta-carotene, a carotenoid partially metabolized to retinol, on plasma lipid concentrations. 31 persons were given 50 mg beta-carotene/d orally for a period of 12 months. At study entry and 1 year later, fasting blood samples were obtained for the measurement of triglycerides, total cholesterol, high-density lipoprotein cholesterol, retinol, and beta-carotene. Daily oral administration of beta-carotene was found not to adversely affect plasma lipid concentrations.


Vitamin A Is Antifungal

Mikhlin et al. (1983) studied the antifungal activity of some derivatives of vitamin A, such as retinal, acetate and retinoic acid.

The antifungal activity of the compounds was documented by their inhibition of fungal spore germination and by areas of growth inhibition of the test organisms on an agar medium. All the compounds possessed antifungal activity against all the fungal pathogens used.

Vitamin A Improves Macrophage
Function Against Fungi

Hatchigian et al. (1989) investigated the effects of vitamin A, on infection in rats. Macrophages of the vitamin A-treated group showed greater phagocyte activity than controls as assessed by the percentage of cells ingesting yeast particles and by the number of particles ingested.

These results indicated that vitamin A in moderate amounts may benefit the host's immune response to infection by enhancing phagocyte cell function.

Vitamin A Protects Against Aflatoxin
(2 Studies)

1. Bhattacharya et al. (1989) found that vitamin A afforded protection against the adverse effects of administered aflatoxin in rats.

2. Goswami et al. (1989) tested nine natural carotenoids (vitamin A) for their ability to modulate the aflatoxin toxicity—formation of DNA adducts—in an in vitro reaction catalyzed by rat liver microsomes. Certain apo-carotenoids, which are precursors of vitamin A, were found to be very efficient in inhibiting the adduct formation. Some other carotenoids—although having less pro-vitamin A activity—also showed a similar inhibitory effect. It was concluded that natural carotenoids could counteract the carcinogenic action of aflatoxin.

Vitamin A Inhibits Aflatoxin
Carcinogenicity (2 Studies)

1. Suphakarn et al. (1983) found that a vitamin-A-(retinyl acetate)-deficient diet increased the occurrence of liver cancer in rats which were exposed to aflatoxin B1. This vitamin A-deficient diet also caused a 29% increased incidence of colon cancer.

Previous studies were pointed out which had shown that colon epithelium from vitamin A-deficient rats binds more aflatoxin than colon epithelium from normal, vitamin A-supplemented animals.

These results suggest that the effect of vitamin A on the metabolism of the carcinogen, particularly on the binding of aflatoxin to cellular macromolecules, may be the mechanism by which vitamin A lessens aflatoxin's carcinogenic potential.

2. Busk and Ahlborg (1982) reported that vitamin A (retinol) exhibits a strong inhibitory effect on the mutagenicity of aflatoxin B1 in the Ames Salmonella/microsome test. Furthermore, this inhibitory effect was exerted by retinol esters such as retinol acetate and retinol palmitate, the latter being the physiological storage form of vitamin A. Vitamin A Prevents Both Promotion

And Initiation Step Of Carcinogenesis

Huang et al. (1982) reported that retinol itself may not have a direct effect on the cellular genetic material, but rather that it may exert its effect possibly by inhibiting the metabolic activation of an indirect mutagen or carcinogen. Thus, the anti-tumor activities of retinoids may not be limited to the widely accepted role of prevention of the promotion step but may also prevent the initiation step of carcinogenesis as well.

Vitamin A May Augment Effect
Of Other Anti-Cancer Drugs

Deng et al. (1988) elucidated the mechanism of tumor prevention of beta-carotene and vitamin A using cell cultures.

Their data clearly showed that the anti-tumor activity of beta-carotene may be attributed to both itself and its degraded compound vitamin A, and that the anti-tumor activity may be effective in inhibiting the initiation of carcinogenesis.

It was concluded that a combination of beta-carotene and other cancer preventive drugs is more effective and safer than individual drugs used alone.

Carotenoid Reduces Aflatoxin
Hepatotoxicity And DNA Binding
(2 Studies)

1. The suppressive effects of crocetin (a natural carotenoid) on the hepatotoxic lesions induced in rats by aflatoxin B1 were documented by Wang et al. (1991A, 1991B). A significant protective effect of crocetin against hepatotoxicity was shown in its ability to decrease the binding of aflatoxin to cellular DNA, an important mechanism of aflatoxin's toxicity.

2. Yu et al. (1994) have also reported that vitamin A decreases the toxicity of aflatoxin by reducing its ability to bind to DNA.

Beta-Carotene Prevents
Aflatoxin-Induced Cancer

Nyandieka et al. (1989) conducted a long-term study in rats to determine the effects of dietary constituents on aflatoxin-induced liver cancer.

It was observed that dietary mixtures containing small quantities of either beta-carotene (vitamin A), ascorbic acid, vitamin E, selenium salt, or uric acid, effectively inhibited the development of aflatoxin-induced liver cancer.

Carotene Inhibits Aflatoxin Carcinogenicity

Nyandieka et al. (1990) investigated the influence of nutritional factors on aflatoxin-induced liver tumors in rats.

When a dose of aflatoxin was given to rats in the absence of any anti-carcinogen, 80 percent of the rats developed liver tumors.

In the presence of beta-carotene (vitamin A), the development of liver tumors was totally inhibited.

Vitamin A Protective Against Mycotoxin-
 Induced Cardiotoxicity And Lethality

Tesoriere et al. (1994) used vitamin A to study its protective action against damage induced in the rat heart through administration of an acute dose of doxorubicin (a mycotoxin). Prevention of doxorubicin-induced cardiomyopathy by vitamin A was evident from the histopathological pattern observed.

The dosage of vitamin A useful to obtain the protective effect appears safe and does not injure the liver, as indicated by light microscopy of the tissue. A survival study showed that pretreatment with 25 IU of vitamin A per kilogram significantly increased the survival rate of the animals.

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