UCLA scientists and colleagues from UC Riverside and the Human BioMolecular Research Institute have found that a form of vitamin D, together with a chemical found in turmeric spice called curcumin, may help stimulate the immune system to clear the brain of amyloid beta, which forms the plaques considered the hallmark of Alzheimer’s disease.

The early research findings, which appear in the July issue of the Journal of Alzheimer’s Disease, may lead to new approaches in preventing and treating Alzheimer’s by utilizing the property of vitamin D3 — a form of vitamin D — both alone and together with natural or synthetic curcumin to boost the immune system in protecting the brain against amyloid beta.

Vitamin D3 is an essential nutrient for bone and immune system health; its main source is sunshine, and it is synthesized through the skin. Deficiencies may occur during winter months or in those who spend a lot of time indoors, such as Alzheimer’s patients.

“We hope that vitamin D3 and curcumin, both naturally occurring nutrients, may offer new preventive and treatment possibilities for Alzheimer’s disease,” said Dr. Milan Fiala, study author and a researcher at the David Geffen School of Medicine at UCLA and the Veterans Affairs Greater Los Angeles Healthcare System.

Using blood samples from nine Alzheimer’s patients, one patient with mild cognitive impairment and three healthy control subjects, scientists isolated monocyte cells, which transform into macrophages that act as the immune system’s clean-up crew, traveling through the brain and body and gobbling up waste products, including amyloid beta. Researchers incubated the macrophages with amyloid beta, vitamin D3 and natural or synthetic curcumin.

The synthetic curcuminoid compounds were developed in the laboratory of John Cashman at the Human BioMolecular Research Institute, (http://www.hbri.org/), a nonprofit institute dedicated to research on diseases of the human brain.Researchers found that naturally occurring curcumin was not readily absorbed, that it tended to break down quickly before it could be utilized and that its potency level was low, making it less effective than the new synthetic curcuminoids.

“We think some of the novel synthetic compounds will get around the shortcomings of curcumin and improve the therapeutic efficacy,” Cashman said.

The team discovered that curcuminoids enhanced the surface binding of amyloid beta to macrophages and that vitamin D strongly stimulated the uptake and absorption of amyloid beta in macrophages in a majority of patients.

Previous research by the team demonstrated that the immune genes MGAT III and TLR-3 are associated with the immune system’s ability to better ingest amyloid beta. In this earlier work, Fiala noted, it was shown that there are two types of Alzheimer’s patients: Type 1 patients, who respond positively to curcuminoids, and Type II patients, who do not.

“Since vitamin D and curcumin work differently with the immune system, we may find that a combination of the two or each used alone may be more effective — depending on the individual patient,” he said.

Fiala noted that this is early laboratory research and that no dosage of vitamin D or curcumin can be recommended at this point. Larger vitamin D and curcumin studies with more patients are planned.

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BOSTON (May 18, 2009) Curcumin, the major polyphenol found in turmeric, appears to reduce weight gain in mice and suppress the growth of fat tissue in mice and cell models. Researchers at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University (USDA HNRCA) studied mice fed high fat diets supplemented with curcumin and cell cultures incubated with curcumin.

“Weight gain is the result of the growth and expansion of fat tissue, which cannot happen unless new blood vessels form, a process known as angiogenesis.” said senior author Mohsen Meydani, DVM, PhD, director of the Vascular Biology Laboratory at the USDA HNRCA. “Based on our data, curcumin appears to suppress angiogenic activity in the fat tissue of mice fed high fat diets.”

Meydani continued, “It is important to note, we don’t know whether these results can be replicated in humans because, to our knowledge, no studies have been done.”

Turmeric is known for providing flavor to curry. One of its components is curcumin, a type of phytochemical known as a polyphenol. Research findings suggest that phytochemicals, which are the chemicals found in plants, appear to help prevent disease. As the bioactive component of turmeric, curcumin is readily absorbed for use by the body.

Meydani and colleagues studied mice fed high fat diets for 12 weeks. The high fat diet of one group was supplemented with 500 mg of curcumin/ kg diet; the other group consumed no curcumin. Both groups ate the same amount of food, indicating curcumin did not affect appetite, but mice fed the curcumin supplemented diet did not gain as much weight as mice that were not fed curcumin.

“Curcumin appeared to be responsible for total lower body fat in the group that received supplementation,” said Meydani, who is also a professor at the Friedman School of Nutrition Science and Policy at Tufts. “In those mice, we observed a suppression of microvessel density in fat tissue, a sign of less blood vessel growth and thus less expansion of fat. We also found lower blood cholesterol levels and fat in the liver of those mice. In general, angiogenesis and an accumulation of lipids in fat cells contribute to fat tissue growth.”

Writing in the May 2009 issue of the Journal of Nutrition, the authors note similar results in cell cultures. Additionally, curcumin appeared to interfere with expression of two genes, which contributed to angiogenesis progression in both cell and rodent models.

“Again, based on this data, we have no way of telling whether curcumin could prevent fat tissue growth in humans.” Meydani said. “The mechanism or mechanisms by which curcumin appears to affect fat tissue must be investigated in a randomized, clinical trial involving humans.”

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This study was funded by a grant from the United States Department of Agriculture. Asma Ejaz, a graduate student who worked on this project received a scholarship grant from the Higher Education Commission of Pakistan.

Ejaz A, Wu, D, Kwan P, and Meydani M. Journal of Nutrition. May 2009; 139 (5): 1042-1048. “Curcumin Inhibits Adipogenesis in 3T3-L1 Adipocytes and Angiogenesis and Obesity in C57/BL Mice. 919-925.”