A cheap regimen of vitamins in use fordecades is seen by scientists as a way to delay the start of Alzheimer'sdisease and dementia, a goal that prescription drugs have failed to achieve.
Drugmakers including Bristol-Myers SquibbCo., Pfizer Inc. (PFE) and Eli Lilly & Co. (LLY) have spent billions ofdollars on ineffective therapies in a so-far fruitless effort to come up with atreatment for dementia and Alzheimer's.
Now, in the latest of a steady drumbeat ofresearch that suggests diet, exercise and socializing remain patients' besthope, a study published today in the Proceedings of the National Academy ofSciences shows that vitamins B6 and B12 combined with folic acid slowed atrophyof gray matter in brain areas affected by Alzheimer's disease.
"You don't have any other options forthese patients, so why not try giving them this cocktail of B vitamins?"says Johan Lokk, a professor and head physician in the geriatric department atKarolinska University Hospital Huddinge in Sweden, who wasn't involved in thestudy.
Alzheimer's disease and dementia mostlyaffect older people. As people live longer, the number afflicted by theconditions is growing. Delaying dementia with an inexpensive vitamin regimenmay help stem the surge in cases, which the World Health Organization predictedwould more than triple from 36 million worldwide in 2010 to 115 million in2050, as well as the cost, estimated at $604 billion in 2010 by Alzheimer'sDisease International.
Vitamin makers and retailers such as Pfizer'sconsumer health-care unit and GNC Holdings Inc. (GNC) in the U.S. and ReckittBenckiser Group Plc and Holland & Barrett Holding Ltd. in Europe stand tobenefit. The Nutrition Business Journal estimates the global market forvitamins, minerals and supplements was $30 billion in 2012 and forecasts saleswill grow 3.6 percent by 2017.
In the PNAS study, researchers tracked 156people ages 70 and older who had mild memory loss and high levels of a proteinpreviously linked to dementia. Among people with elevated homocysteine, thestudy found that the amount of gray matter declined 5.2 percent in those takinga placebo, compared with 0.6 percent in those who took the vitamin cocktail.The supplements cost about 30 cents a day in pharmacies and health-food stores.
"It's the first and onlydisease-modifying treatment that's worked," said A. David Smith, professoremeritus of pharmacology at Oxford University in England and senior author ofthe study. "We have proved the concept that you can modify the disease."
The U.S. Food and Drug Administration hasn'tcleared new drugs for memory loss conditions in a decade. Approved medicinessuch as Eisai Co.'s Aricept ease symptoms without slowing or curing dementia. Ajoint U.S.-European Union task force in 2011 found that all disease-modifyingtreatments for Alzheimer's in the previous decade failed late-stage trials "despiteenormous financial and scientific efforts."
Since then, at least four more experimentaltreatments have failed. New York-based Bristol-Myers dropped development ofavagacestat in December after data showed the therapy wasn't effective enoughto move into the final stage of testing. Solanezumab, from Indianapolis-basedLilly, failed to meet the main goal of two large studies last year, though thecompany plans to conduct further research.
Bapineuzumab from Pfizer, Johnson &Johnson and Elan Corp. failed to improve patients' memory or thinking,according to test results released in August. This month, Baxter InternationalInc. said Gammagard, which is used to help patients with immune disorders, didn'thelp Alzheimer's patients in a late-stage study.
Meanwhile, scientists are exploring the useof experimental drugs to prevent Alzheimer's. Independent trials will beginthis year and run for three to five years.
Older people's brains shrink about 0.5percent a year from the age of 60, and faster in people with vitamin B12deficiency, mild cognitive impairment or Alzheimer's disease, Smith said. Ifthat pace can be significantly slowed before full-blown Alzheimer's develops,it may delay the disease's progression so that older people can enjoy betterlives until they die from another cause.
"If you delay the onset by five years,you can halve the number of people dying from it," says Jess Smith, aresearch communications officer at the Alzheimer's Society, a U.K. charity. Sheisn't related to A. David Smith.
The Oxford group studied people in theOxford, England, area who had mild cognitive impairment, also known as MCI, orsome memory loss. One in six people over 70 have MCI and about half of thosedevelop dementia within five years, A. David Smith said. Alzheimer's accountsfor 50 percent to 80 percent of all dementias, according to the Alzheimer'sAssociation.
Study volunteers were given either aplacebo or 0.5 milligrams of vitamin B12, 20 milligrams of vitamin B6 and 0.8milligrams of folic acid. Their brains were scanned using magnetic-resonanceimaging and blood levels of the protein homocysteine were measured at the startof the trial and two years later. The MRI scans compared how much gray matterwas lost in brain regions most affected by Alzheimer's disease.
"It's a big effect, much bigger thanwe would have dreamt of," A. David Smith said. "I find thespecificity of this staggering. We never dreamt it would be so specific."
The research reinforces previous findingsthat supplements slowed brain atrophy and cognitive decline in the group.
Smith and his colleagues at Oxford reportedin 2010 that the atrophy rate in patients' whole brains was reduced about 30percent in those taking the vitamins and 53 percent in those on the vitamins whoalso had elevated homocysteine. They published study results in 2012 of memorytests that found people on the treatment who had high homocysteine were 69percent likelier to correctly remember a list of 12 words.
The studies, known as Vitacog, were fundedby seven charities and government agencies and vitamin maker Meda AB (MEDAA) ofSolna, Sweden. Smith is an inventor on three patents held by Oxford Universityfor B vitamin formulations to treat Alzheimer's disease or MCI.
Vitamin B12 is found in liver, fish andmilk and folic acid in fruit and vegetables. Deficiency of folate and Bvitamins is already linked to dementia. Researchers such as Smith are studyingwhether less-than-optimal levels of B vitamins and folic acid contribute to itsdevelopment.
"If you have somebody who has outrightAlzheimer's disease, this isn't really going to help them much," saidJoshua Miller, a professor in the department of nutritional sciences at RutgersUniversity in New Brunswick, New Jersey. "If you can catch them at anearlier level, they may be able to benefit from it but only if you haveelevated homocysteine."
A U.S. study published in 2008 found thatpeople who had moderate or severe Alzheimer's didn't benefit from thesupplements. There's no evidence that B vitamins enhance cognitive function inhealthy people, A. David Smith said.
Doctors in Sweden began measuringhomocysteine in people who report declining memory about two years ago, saidLokk at Karolinska. Swedish patients with high homocysteine are given folicacid and B vitamins, even if they aren't deficient.
"We think the increased homocysteinelevel could be deleterious to the brain," Lokk said. "We wanted to beon the offensive in diagnosing and treating patients. In our opinion, it isharmless and cheap."
Vitamin B12 is probably the key to slowingthe brain's shrinkage and cognitive decline, Miller said. The FDA said in 1998that folic acid had to be added to breads, cereals and other products that useenriched flour, to reduce neural tube defects such as spina bifida in newborns.A study by Miller and his colleagues in people of Mexican and South and CentralAmerican ancestry age 60 and older in Sacramento, California, the followingyear found their homocysteine was still high and that very few had low folate.Europe doesn't require fortification of flour and breads.
Other studies have suggested that folicacid stimulates the growth of existing cancer cells. The data aren'tconclusive, so people at risk of cancer should avoid extra folic acid, Lokksaid. This could include men older than 70 who may have undetected prostatecancer, A. David Smith said.
"We're not suggesting everyone over 60take this; we're suggesting it should be targeted to people over 70 with highhomocysteine and memory problems," he said.
It's too early to put everyone on Bvitamins, said Jess Smith of the Alzheimer's Society.
"The evidence for supplementing isjust not there yet," she said. "We need bigger studies and moreevidence that looks at what homocysteine is doing and what is actually going onin the brain."
A. David Smith agrees. He plans a study ofB vitamins in 1,200 people over 70 with MCI and elevated homocysteine. He needs6 million pounds ($9.1 million) to pay for it. Miller plans another large studyand wants to see if folic acid in flour in the U.S. leads to different resultsthere. Meanwhile, the lack of blockbuster-drug potential presents fundinghurdles.
"The pharmaceutical companies aren'tgoing to make any money on this and the supplement companies aren't going tohave enough money to do it," Miller said. "This would have to begovernment-funded. I'm just not sure the climate is right for it now."
To contact the reporter on this story: Andrea Gerlin in London at [email protected].
To contact the editor responsible for thisstory: Phil Serafino at [email protected].