Dark-hued fruits, veggies are good for the brain (Les fruits de couleurs foncée, les légumes sont bon pour le cerveau)

Neuroscientist James A. Joseph is one of those lucky people who gets to have his cake and eat it, too. At the Human Nutrition Research Center on Aging at Tufts University (Medford, Massachusetts), Joseph revels in his research demonstrating that dark-hued fruits and vegetables, especially blueberries, are just about the best foods you could consume for inoculating brain and body against the ravages of time.

Every morning before heading to his Boston lab, Joseph pours himself a glass of ruby-red pomegranate juice and then chases it with roughly a cup of blueberries. Not just any blueberries but wild ones, flash-frozen to preserve the phytochemicals that research shows are particularly abundant in the tiny fruits that fend for themselves against the short growing season and harsh conditions of northern climates. There they stretch themselves across stony fields so inhospitable they're known as blueberry barrens.

At work, studying the nutritional modulation of cognitive decline, Joseph delineates the bioactive properties of the fruits he calls "brainberries." Yes, blueberries provide traditional nutrients - carbohydrates, fiber, vitamins C and E, manganese. But the deeply pigmented flavonoid phytochemicals known as anthocyanidins found in the fruit are not nutrients in the strict sense of the word. They are, however, biologically active in surprisingly sophisticated ways: intervening at the molecular level along signaling pathways to turn vital genes on or off in brain cells, making brain cells maximally responsive to incoming messages from other cells, even prompting the growth of new nerve cells.

Cumulatively, the berries produce antioxidant effects, neutralizing cellular damage created by free radicals of oxygen and blocking pathways by which oxidative stress damages cells. Perhaps more important, they function as anti-inflammatory agents to preserve cardiovascular as well as brain integrity. "Oxidative stress and inflammation are the evil twins of brain aging," Joseph insists.

Berries make a difference at the behavioral level, too. Aging rats fed the equivalent of a cup of berries a day navigate water mazes like pups, with few mistakes of memory. Plus, as Joseph told a meeting of the Metropolitan (New York) Area Geriatric Society, the animals were powered by leg muscles "that look like those in the legs of young rats."

As good as blueberries are by themselves, Joseph finds, they are more biologically extravagant in combination with certain other foods. Blueberries have a particularly complex relationship with fats - both the good kind and the bad.

Eaten, for example, with oil-rich walnuts or avocados, the berries act synergistically to keep brain cell membranes youthfully flexible - a feat of wide impact since every flicker of thought or intentional movement starts with a transaction across a brain cell membrane. Then, too, blueberries lower the body's burden of cholesterol, minimizing the threat of atherosclerosis in the blood vessels that supply heart and brain.

Walnuts, Joseph finds, contain both polyphenols, like dark berries, and omega-3 fatty acids. They are especially rich in the omega-3 fat known as alpha-linolenic acid. Nerve cell membranes, he explained to the New York conference, are host to a wide array of receptors, such as those for serotonin and other neurotransmitters; receptors are the gateway to nerve cells. But with age, the membranes become rigid and blunt the actions of receptors.

"Together, the polyphenols in berries and walnuts and the fatty acids in the walnuts fluidize the nerve cell membrane," Joseph reported. "They make it more responsive to a wide array of signals," increasing the efficiency of all transactions. The membrane effects are at least as powerful as the antioxidant effects that have already earned blueberries a place at the well-appointed table.

Walnuts may amplify the effects of richly hued berries in still other ways. The equivalent of one ounce of walnuts - the amount recommended for heart health - may help block inflammation at the cellular level, a process now implicated in cardiovascular disease, Alzheimer's disease, and other degenerative processes of aging. "All this is reversible," Joseph insists. "The effects of natural combinations such as walnuts and blueberries - or strawberries or blackberries - are powerful."

In a study led by Joseph's occasional collaborator, Canadian Wilhelmina Kalt, researchers found that a diet moderately rich in blueberries also directly affects cholesterol transport in the body. The net effect is a decrease in total cholesterol and especially of artery-clogging LDL, or low-density lipoprotein, cholesterol.

Kalt's study, published recently in the British Journal of Nutrition, is the first to document lipid-lowering effects of blueberries. The investigators called the results especially notable because they were achieved in pigs - models of human heart disease - with "doses that could reasonably be achieved in the adult human diet," about a cup of berries a day. The anthocyanins had the greatest cholesterol-lowering effect in those animals fed diets rich in other plant foods as well. Kalt, a Nova Scotia-based researcher with Agri-Food

Canada, spends part of every summer meeting with Joseph and his "brainberry group" at the halfway point, in Maine.

"We have fun in here," Joseph says of his research lab, filled with baskets of fruit. "And it's fun to talk about. It's something that people can use right now. Adding walnuts and berries or purple grape juice to the diet could delay the onset of the degenerative diseases of aging."

It's never too late

The right dietary changes have immediate brain payoffs at any age, contends Joseph. They can slow down neural aging. He advises:

- Eat plenty of colorful fruits and vegetables, which are high in antioxidants, along with nuts such as almonds, walnuts, and pecans.

- Spice up your food with circumin, which has neuroprotective effects.

- Consume foods rich in folic acid to preserve memory.

- Maintain zinc levels to help ward off Alzheimer's disease.

Novartis: une étude menace le FTY720 (Fingolimod) contre la sclérose en plaques (BCZ)

Zurich (AWP) - Une étude de chercheurs américains, parue dans la revue "Nature" (édition du 14 août), pourrait bien mettre un terme à la carrière du produit candidat FTY720 (Fingolimod) de Novartis pour le traitement de la sclérose en plaques (MS). L'étude montre que le FTY720 ne freine pas durablement le système immunitaire mais, au contraire, l'active d'une façon non désirée, note Michael Nawrath de la Banque cantonale de Zurich (BCZ) dans un commentaire. Le Fingolimod passe actuellement des tests de phase III dans une indication contre la MS.

La BCZ n'attribue "presque plus aucune chance" au Fingolimod en tant que médicament. La substance pourrait à la rigueur devenir un virostatique, mais cela demanderait de lancer une batterie de tests supplémentaires. Une commercialisation n'interviendrait alors qu'en 2015, "dans le meilleur des cas".

L'étude américaine montre que Fingolimod a un effet antiviral. La substance freine le système immunitaire, puis le réactive, ce qui la rend inapte à combattre la MS et provoque de nombreux effets secondaires, note la BCZ.

Selon M. Nawrath, 2,5 mio de personnes sont atteintes de MS. Le marché devrait croître de 5% par an. Le potentiel de chiffre d'affaires d'un médicament comme le Fingolimod atteint les 2,5 mrd USD en 2014, soit 20% des parts de marché, estime la BCZ. Les quatre interférons et le Tysabri utilisés jusqu'ici ont permis de réaliser un chiffre d'affaires de 7,75 mrd USD en 2007.

Certains analystes attendaient la commercialisation du Fingolimod pour 2010; elle aurait dû compenser de 2010 à 2012 les pertes liées à l'échéance de certains brevets.

La BCZ n'a pas inclus le Fingolimod dans ses prévisions de chiffre d'affaires. Mais tous les analystes ne vont pas forcément procéder ainsi, ce qui risque de conduire à "d'importantes révisions des prévisions de bénéfices" au cas où l'indication de MS devait être abandonnée, lit-on dans le commentaire de la BCZ.

La BCZ attribue "pondérer au marché" au titre Novartis.

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(AWP/18 août 2008 13h36)

Recombinant hepatitis B vaccine and the risk of multiple sclerosis

NEUROLOGY 2004;63:838-842
© 2004 American Academy of Neurology

Recombinant hepatitis B vaccine and the risk of multiple sclerosis
A prospective study
Miguel A. Hernán, MD, DrPH, Susan S. Jick, DSc, Michael J. Olek, DO and Hershel Jick, MD

From the Department of Epidemiology (Dr. Hernán), Harvard School of Public Health, Boston; Boston Collaborative Drug Surveillance Program (Drs. Susan S. Jick and Hershel Jick), Boston University, Lexington, MA; and Department of Neurology (Dr. Olek), College of Medicine, University of California, Irvine.

Address correspondence and reprint requests to Dr. Miguel Hernán, Department of Epidemiology, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA 02115; e-mail: miguel_hernan@post.harvard.edu

Background: A potential link between the recombinant hepatitis B vaccine and an increased risk of multiple sclerosis (MS) has been evaluated in several studies, but some of them have substantial methodologic limitations.

Methods: The authors conducted a nested case-control study within the General Practice Research Database (GPRD) in the United Kingdom. The authors identified patients who had a first MS diagnosis recorded in the GPRD between January 1993 and December 2000. Cases were patients with a diagnosis of MS confirmed through examination of medical records, and with at least 3 years of continuous recording in the GPRD before their date of first symptoms (index date). Up to 10 controls per case were randomly selected, matched on age, sex, practice, and date of joining the practice. Information on receipt of immunizations was obtained from the computer records.

Results: The analyses include 163 cases of MS and 1,604 controls. The OR of MS for vaccination within 3 years before the index date compared to no vaccination was 3.1 (95% CI 1.5, 6.3). No increased risk of MS was associated with tetanus and influenza vaccinations.

Conclusions: These findings are consistent with the hypothesis that immunization with the recombinant hepatitis B vaccine is associated with an increased risk of MS, and challenge the idea that the relation between hepatitis B vaccination and risk of MS is well understood.

Received March 31, 2004. Accepted in final form May 8, 2004.


Recombinant_hepatitis_B_vaccine_and_the_risk_of_MS.pdf