High Intake of Carotenoids Linked to Reduced ALS Risk

Pauline Anderson

January 29, 2013

Consuming foods high in carotenoids, such as β-carotene and lutein, found in brightly colored foods such as spinach, kale and carrots, may help ward off amyotrophic lateral sclerosis (ALS), a new study comprising more than a million participants and over 1000 cases of ALS has shown.

"Our findings suggest that consuming carotenoid-rich foods could help prevent or delay the onset of ALS," said lead author Kathryn C. Fitzgerald, ScM, a doctoral student in the Department of Nutrition at Harvard School of Public Health in Boston, Massachusetts.

The analysis also found that high intake of dietary vitamin C or vitamin C supplements had no effect on ALS risk.

The study was published online January 29 in the Annals of Neurology, a journal of the American Neurological Association and Child Neurology Society.

Nutrient Intake

The study was a pooled analysis of 5 large prospective studies: the Nurses Health Study, the Health Professionals Follow-up Study, the Cancer Prevention Study II–Nutrition Cohort, the Multiethnic Cohort Study, and the National Institutes of Health–Association of American Retired Persons Diet and Health Study.

Study participants completed health questionnaires in which they reported any new diagnosis of specific medical conditions, including ALS. The study included only ALS cases confirmed by a neurologist with experience in ALS. ALS deaths were documented through linkage with the National Death Index.

Participants reported routine intake of each food during the preceding year on a scale ranging from never to less than 1 time per month to 6 servings or more per day. Experts calculated nutrient intake on the basis of frequency of consumption and portion size. As well, they collected detailed information on the use of multivitamins and of vitamin C and E and β-carotene supplements.

The analysis included 1093 cases of ALS in 1,053,575 men and women. Those with high dietary carotenoid intake tended to exercise more, have more advanced education and higher intake of dietary vitamin C, and were generally more likely to take vitamin C and E supplements.

The results showed that a high intake of total dietary carotenoids was associated with a lower risk for ALS. Those in the highest quintile experienced a 25% lower risk for ALS compared with those in the lowest (relative risk [RR], 0.75; 95% confidence interval [CI], 0.61 - 0.91; P for trend = .004).

The effect was stronger among participants who had never smoked; smoking modulates carotenoid levels. Here, the RR comparing the highest to the lowest quintiles was 0.65 (95% CI, 0.44 - 0.97).

β-Carotene and Lutein

Individually, β-carotene and lutein were associated with reduced risk for ALS. The pooled multivariate RR comparing persons in the top quintile with those in the bottom quintile for intake was 0.85 (95% CI, 0.64 - 1.13; P = .03) for β-carotene and 0.79 (95% CI, 0.64 - 0.96; P = .01) for lutein.

Dark green vegetables, such as spinach and kale, and brightly colored foods, such as carrots, pumpkins, sweet potatoes, and egg yolks, are rich sources of .β-carotene and lutein.

A post hoc analysis using deciles showed a 26% and 30% reduction in risk for ALS for the top compared with the bottom decile of β-carotene and lutein intake, respectively.

Results were similar in a lagged analysis that excluded the first 4 years of follow-up in each cohort, which accounted for the possibility that ALS symptoms were present at the time participants completed dietary questionnaires.

Other carotenoids — α-carotene, β-cryptoxanthin, and lycopene — were not individually associated with risk for ALS in the study.

Similarly, there was no association between supplemental use of vitamin C, or dietary vitamin C intake, and the risk for ALS. Fitzgerald pointed out that vitamin C is a water-soluble vitamin and therefore has different biological properties than carotenoids.

There was also no significant evidence of effect modification by vitamin E supplement use, suggesting that vitamin E alone can't explain the association.

An earlier pooled analysis of 5 prospective studies from researchers in the Department of Nutrition at Harvard School of Public Health showed that taking vitamin E supplements for more than 5 years or consuming a diet rich in this vitamin is associated with a reduced risk for ALS. That study appeared in the March 15, 2011, issue of the American Journal of Epidemiology and was reported at that time by Medscape Medical News.

The current results are of note because the study is one of the largest to look at dietary factors and risk for ALS, Fitzgerald noted. "Finding possible modifiable risk factors for ALS is important," she said.

According to Fitzgerald, the most plausible explanation for the association between certain carotenoids and ALS risk is their antioxidant activity, occurring primarily through quenching of multiple types of reactive oxygen species. This, write the authors, "may help prevent mitochondrial distress, interruptions of glial glutamate transport, protein aggregation, or inflammation, thereby preventing motor neuron death."

It's not clear from this study how often or how many brightly colored fruits and vegetables it's necessary to consume to lower the risk for ALS. "Right now there's no specific amount, or we can't say how much you should eat," said Fitzgerald.

A limitation of the study is that it used ALS deaths instead of cases, but the authors pointed out that deaths are a "reasonable proxy for incidence" because of the rapidly progressive nature of ALS.

The study was supported by the National Institutes of Health. Ms. Fitzgerald reports grants/grants pending from the National Institutes of Health. For conflicts of interest of other authors, see original paper.

Ann Neurol. Published online January 29, 2013. Abstract

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