Vitamin D omega 3 may help clear amyloid plaques found in Alzheimers

A team of academic researchers has pinpointed how vitamin D3 and omega-3 fatty acids may enhance the immune systems ability to clear the brain of amyloid plaques, one of the hallmarks of Alzheimers disease.

In a small pilot study published in the Feb. 5 issue of the Journal of Alzheimers Disease, the scientists identified key genes and signaling networks regulated by vitamin D3 and the omega-3 fatty acid DHA (docosahexaenoic acid) that may help control inflammation and improve plaque clearance.

Previous laboratory work by the team helped clarify key mechanisms involved in helping vitamin D3 clear amyloid-beta, the abnormal protein found in the plaque. The new study extends the previous findings with vitamin D3 and highlights the role of omega-3 DHA.

"Our new study sheds further light on a possible role for nutritional substances such as vitamin D3 and omega-3 in boosting immunity to help fight Alzheimers," said study author Dr. Milan Fiala, a researcher at the David Geffen School of Medicine at UCLA.

For the study, scientists drew blood samples from both Alzheimers patients and healthy controls, then isolated critical immune cells called macrophages from the blood. Macrophages are responsible for gobbling up amyloid-beta and other waste products in the brain and body.

The team incubated the immune cells overnight with amyloid-beta. They added either an active form of vitamin D3 called 1alpha,25–dihydroxyvitamin D3 or an active form of the omega-3 fatty acid DHA called resolvin D1 to some of the cells to gauge the effect they had on inflammation and amyloid-beta absorption.

Both 1alpha, 25-dihydroxyvitamin D3 and resolvin D1 improved the ability of the Alzheimers disease patients macrophages to gobble-up amyloid-beta, and they inhibited the cell death that is induced by amyloid-beta. Researchers observed that each nutrition molecule utilized different receptors and common signaling pathways to do this.

Previous work by the team, based on the function of Alzheimers patients macrophages, showed that there are two groups of patients and macrophages. In the current study, researchers found that the macrophages of the Alzheimers patients differentially expressed inflammatory genes, compared with the healthy controls, and that two distinct transcription patterns were found that further define the two groups: Group 1 had an increased transcription of inflammatory genes, while Group 2 had decreased transcription. Transcription is the first step leading to gene expression.

"Further study may help us identify if these two distinct transcription patterns of inflammatory genes could possibly distinguish either two stages or two types of Alzheimers disease," said study author Mathew Mizwicki, an assistant researcher at the David Geffen School of Medicine at UCLA.

While researchers found that 1alpha,25-dihydroxyvitamin D3 and resolvin D1 greatly improved the clearance of amyloid-beta by macrophages in patients in both groups, they discovered subtleties in the effects the two substances had on the expression of inflammatory genes in the two groups. In Group 1, the increased-inflammation group, macrophages showed a decrease of inflammatory activation; in Group 2, macrophages showed an increase of the inflammatory genes IL1 and TLRs when either 1alpha,25-Dihydroxyvitamin D3 or resolvin D1 were added.

More study is needed, Fiala said, but these differences could be associated with the severity of patients nutritional and/or metabolic deficiencies of vitamin D3 and DHA, as well as the omega-3 fatty acid EPA (eicosapentaenoic acid).

"We may find that we need to caully balance the supplementation with vitamin D3 and omega-3 fatty acids, depending on each patient in order to help promote efficient clearing of amyloid-beta," Fiala said. "This is a first step in understanding what form and in which patients these nutrition substances might work best."

According to Fiala, an active (not oxidized) form of omega-3 DHA, which is the precursor of the resolvin D1 used in this study, may work better than more commercially available forms of DHA, which generally are not protected against the oxidation that can render a molecule inactive.

The next step is a larger study to help confirm the findings, as well as a clinical trial with omega-3 DHA, the researchers said.

High dose Vitamin D Prevents Fractures in Elderly

NEW YORK (Reuters Health) - A new analysis of nearly a dozen studies testing vitamin D in older individuals has concluded that it takes a daily dose of at least 800 international units (IU) to consistently prevent broken bones.

A dose that high was found to reduce the risk of hip fracture by 30 percent and other breaks by 14 percent. Lower doses didnt have any effect.

The report, published in the New England Journal of Medicine, also suggests that too much calcium -- perhaps more than 1,000 milligrams (mg) per day -- can weaken the benefit.

"These hip fractures cost a lot and are a really serious event. They are usually the end of independent life for a senior person; 50 percent do not regain their mobility. Reducing the risk by 30 percent with just a vitamin supplement would be an enormous public health opportunity," study researcher Dr. Heike Bischoff-Ferrari of University Hospital Zurich in Switzerland told Reuters Health.

The Institute of Medicine recommends that most adults get 1,000 to 1,200 mg of calcium per day and 600 to 800 IU of vitamin D. It sets a recommended upper limit at 2,000 mg of calcium and 4,000 IU of vitamin D.
Bischoff-Ferrari said the lack of benefit seen in other studies "may be explained by adherence to treatment and vitamin D supplements taken outside the study medication."

Dr. Richard Bockman, a hormone expert at the Hospital for Special Surgery in New York, said the findings are an important counterbalance to last months widely-reported recommendation by the U.S. Preventive Services Task Force.

The government-backed task force advised against taking doses of less than 400 IU of vitamin D with 1,000 mg of calcium and concluded the evidence was unclear for higher doses. It also said the supplements carry a risk of side effects such as kidney stones.

Bockman said the best trial is a 2003 study, known as the Trivedi trial, in which volunteers received an average of 800 IU per day as a single 100,000 IU dose every four months.

"It clearly showed a reduction in fracture risk in people who were getting vitamin D," he said.

In an editorial, Dr. Robert Heaney of Creighton University Medical Center in Omaha, Nebraska, said the problem with the conflicting studies may be that most have failed to consider each persons vitamin D levels to start with.

Giving it to people who already have enough, or not giving enough to people with very low levels, may show no benefit, he said.

"In this regard, as in several other respects, nutrients are unlike drugs. Once an adequate concentration has been achieved, additional intake has no effect," said Heaney.

Bischoff-Ferrari said the new results came without directly including the Trivedi results. "The authors lost the data sets to a computer accident," she said.

The new analysis is based on 11 trials that tested various regimens of oral vitamin D in people age 65 and older, mostly women, against an inactive placebo. Some of the trials also included calcium.

Overall, there were 4,881 hip and other fractures (not including breaks of the spine) among more than 31,000 people.

Vitamin D did not cut the rate of hip fracture significantly, and the drop in other fractures was small. When the researchers looked at people getting the highest doses of the vitamin, typically 800 IU daily, the benefits were clearer, with a 30-percent drop in hip fractures and 14-percent decline in other broken bones.

"Notably, there was no reduction in the risk of hip fracture at any actual intake level lower than 792 IU per day," the researchers said.

The benefits at the higher dose were seen regardless of age, additional calcium intake, whether the patients lived at home or in an institution, and baseline levels vitamin D.

Bischoff-Ferrari said the clearest impact was seen in nursing home patients, who were given the highest doses of vitamin D and regularly took their pills because the nurses were giving them.

Just as important is the discovery that too much calcium - more than 1,000 mg per day - may dilute vitamin Ds benefits to bones, she said. Because many supplements contain 1,000 mg, the calcium people get in their diets may send people over the limit.

"This is a very, very important public health message," Bischoff-Ferrari said. "There are still doctors around who are giving calcium without vitamin to hip fracture patients. Imagine giving a calcium supplement and increasing the fracture risk."

In an earlier study, she added, fewer than 10 percent of the people coming into the hospital for a hip fracture had been taking the vitamin. And 60 percent of them had suffered another fracture in the prior decade, yet "the red flag is not coming up."

"In the medical world, vitamin D seems like a very low priority. It may be the lack of lobbying for it, the fact that it costs almost nothing" and some people think its too good to be true, she said. "But the data are impressive."

SOURCE: http://bit.ly/NmCWUm New England Journal of Medicine, July 5, 2012.