Hypocholesteremia Induced by Orotic Acid: Dietary Effects and Species Specificity

Harden, Kathryn K.; Robinson, James L.

doi:10.1093/jn/114.2.411

Cited by 16 publications

(2 citation statements)

References 29 publications

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“…Furthermore, recovery of initial A␤ levels can be monitored easily after drug removal. Importantly, guinea pigs are well-established animals for lipid physiology studies as they offer several advantages over the use of mice because they are more closely related to the human situation (38)(39)(40)(41). Unlike mice or rats, guinea pigs have the human A␤ sequence.…”

Section: Resultsmentioning

confidence: 99%

Simvastatin strongly reduces levels of Alzheimer's disease β-amyloid peptides Aβ42 and Aβ40 in vitro and in vivo

Faßbender

Simons

Bergmann

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

1,040

724

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Recent epidemiological studies show a strong reduction in the incidence of Alzheimer's disease in patients treated with cholesterol-lowering statins. Moreover, elevated A␤42 levels and the 4 allele of the lipid-carrier apolipoprotein E are regarded as risk factors for sporadic and familial Alzheimer's disease. Here we demonstrate that the widely used cholesterol-lowering drugs simvastatin and lovastatin reduce intracellular and extracellular levels of A␤42 and A␤40 peptides in primary cultures of hippocampal neurons and mixed cortical neurons. Likewise, guinea pigs treated with high doses of simvastatin showed a strong and reversible reduction of cerebral A␤42 and A␤40 levels in the cerebrospinal fluid and brain homogenate. These results suggest that lipids are playing an important role in the development of Alzheimer's disease. Lowered levels of A␤42 may provide the mechanism for the observed reduced incidence of dementia in statin-treated patients and may open up avenues for therapeutic interventions.A part from age, environmental factors have only slight influence on the incidence of Alzheimer's disease (AD). Very recently, two independent reports showed a strong decrease in the incidence of AD and dementia for patients that were treated with statins (1, 2). Both studies were retrospective, and statins were not given in any relation to dementia. Usually statins are prescribed for treatment of elevated serum cholesterol levels in patients. They reduce cholesterol levels by inhibiting the bottleneck enzyme of cholesterol synthesis, 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase. They are widely used drugs, well characterized and considered to be very safe for long-time treatment, and approved for use in elderly patients (3, 4).The 4 allele of the apolipoprotein E (apoE) is the major genetic risk factor for AD (5). Several lines of evidence indicate that apoE 4 and statins have a related influence on AD. The normal cellular function of apoE is uptake and delivery of lipids. The isoform apoE 4 correlates with an increased risk for atherosclerosis (6) and amyloid plaque formation (7). Moreover, elevated cholesterol uptake increases amyloid plaque formation or amyloid deposition (8,9). This correlation may be extended to A␤ production, since cellular cholesterol levels affect neuronal A␤ production in vitro (10). Initially, A␤ has been a focus of AD research, because it was found to be the major constituent of the amyloid plaque. It is unknown whether the amyloid plaque is actively involved in the neurodegenerative process in AD or instead is a consequence of the disease process. More recently, however, A␤ has been a focus of AD research not because of it presence in the amyloid plaque, but because an overproduction of a minor A␤ isoform, A␤42, is linked to all identified inherited forms of AD (11-13).A␤ is produced during normal cellular processing of the Alzheimer amyloid precursor protein (APP) (14) by ␤-secretase and ␥-secretase (15). While the majority of all A␤ isoforms produced is A␤40, Ϸ10% of total A␤ ...

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Section: Resultsmentioning

confidence: 99%

Simvastatin strongly reduces levels of Alzheimer's disease β-amyloid peptides Aβ42 and Aβ40 in vitro and in vivo

Faßbender

Simons

Bergmann

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

1,040

724

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“…In addition to fermented milks, unfermented milk is also known to exhibit hypocholesteremic properties. In bovine milk hydroxymethylglutaric, uric and orotic acids have been identified as in-hibitors of cholesterol biosynthesis [126][127][128][129][130].…”

Section: Anticholesteremic Factorsmentioning

confidence: 99%

Therapeutic role of dietary lactobacilli and lactobacillic fermented dairy products

Fernandes

Shahani

Amer³

1987

FEMS Microbiology Letters

198

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Lactic acid bacteria present in the human and animal gut are introduced through fermented milk products, food and feed supplements containing viable bacteria. Lactobacillus species, such as L. acidophilus, L. bulgaricus, L. lactis along with B. bifidum and Streptococcus faecium constitute an integral part of the healthy gastro‐intestinal microecology and are involved in the host metabolism. They impart nutritional and therapeutic benefits to the consumer. The vitamins and enzymes produced by the lactic acid bacteria contribute to host metabolism. The antimicrobial substances produced by these bacteria control the proliferation of undesired pathogens. They also elaborate enzymes that aid host metabolism. This is particularly true in case of lactase nonpersistent individuals. Their anticholesteremic properties assist in lowering serum cholesterol. It has been suggested that the tumor suppression trait of these microbes reduces the incidence of colon cancer.

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Influence of Diet on Various Disorders

Frape¹

1987

The Future of Predictive Safety Evaluation

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Hypocholesteremia Induced by Orotic Acid: Dietary Effects and Species Specificity

Cited by 16 publications

References 29 publications

Simvastatin strongly reduces levels of Alzheimer's disease β-amyloid peptides Aβ42 and Aβ40 in vitro and in vivo

Simvastatin strongly reduces levels of Alzheimer's disease β-amyloid peptides Aβ42 and Aβ40 in vitro and in vivo

Therapeutic role of dietary lactobacilli and lactobacillic fermented dairy products

Influence of Diet on Various Disorders

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