PD and diet

Recently, at a talk regarding PD in Brunswick, a common question came up as to whether diet influences the disease.  I gave sort of a stock answer, in that no dietary intervention has been proven to treat the condition, but that there are several points to consider about diet (see, for example, the article in MPDN about constipation).  Here, I will review some other issues.

Not surprisingly, the data seems to favor eating a healthy diet.  Many ask, “What is a healthy diet?”  That is a complex question.  Most studies seem to point to something akin to the Mediterranean diet, which contains significant olive oil, grains, vegetables, fruits, potatoes, seeds, nuts, legumes, and fish; and generally lower intake of red meats, poultry, dairy, and alcohol (though small amounts of red wine can be beneficial).  Numerous observations have been made regarding longevity and the reduction of cardiovascular or metabolic diseases among those who eat this way.

These observations have led investigators to study diet for improving health and preventing disease.  The DASH diet (Dietary Approach to Stop Hypertension) is based on the Mediterranean diet, though using relatively more low-fat dairy and less fish.  The MIND diet (Mediterranean–DASH Intervention for Neurodegenerative Delay) takes elements from both diets and increases consumption of berries, nuts, and beans. A meta-analysis, which is an in-depth review of multiple similar studies, looked at 14 prospective trials totaling thousands of participants in the U.S., Greece, Europe, and Australia (1).  In these trials, people were followed from 3.7 to 18 years and had lower rates of Alzheimer disease.  One of the studies, conducted by the World Health Organization Study Group, followed more than 130,000 health care professionals for 16 years, and showed that those who ate a Mediterranean diet had lower rates of PD (2).  Studies of older people who followed the MIND diet showed less cognitive decline at a 4.7-year follow-up (3, 4).

The PREDIMED study included 522 people aged 55-80 who were at high risk for cardiovascular disease (5). These people were randomly assigned to one of three diets: a Mediterranean diet with supplemental extra-virgin olive oil (EVOO), a Mediterranean diet with supplemental mixed nuts, or a regular diet with reduced dietary fat.  Heart attack, stroke, and death from cardiovascular causes were all reduced in those eating the diet with EVOO, and those people scored higher on the Mini-Mental State Examination (MMSE) and the clock-drawing test at 6.5 years.

In a four-month study, 124 participants with high blood pressure started either a DASH diet, or aerobic exercise and a DASH diet (6).  Those with the combined approach had better psychomotor speed (basically, a measure of the time for the connection between thought and movement).  Though none of these patients were noted to have PD, the finding is interesting because one of the problems with PD is a decrease in psychomotor speed.

In a large population study of 1,260 people with cardiovascular risk factors for dementia, the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) (7), participants were chosen who had average, or slightly lower than average, cognitive performance for age, and were randomly assigned to a combination of diet, exercise, cognitive training, and vascular risk monitoring, or to a health advice control group.  The diet included fruit, vegetables, whole-grain cereals, low-fat milk, low-fat meat, low sugar, margarine instead of butter, and two or more portions of fish per week.  Participants underwent a group of 14 neuropsychological tests. During the 24-month follow-up period, composite scores were 25% higher in the intervention group than those who received advice alone.  Executive functioning, which includes problem solving, critical analysis, and processing speed, were better in the intervention group.

There is some data that caffeine consumption may decrease risk of PD.  Over 8,000 men were followed for 30 years in the Honolulu Heart Program (8). Incidence of PD decreased with amount of coffee intake:  the more coffee consumed, the lower the risk of PD.  Similar data was found among those that consumed caffeine from sources other than coffee, such as tea. The National Institutes of Health-AARP Diet and Health Study prospectively examined whether caffeine intake was associated with lower risk of PD among over 300,000 men and women (9).  The effect was equal, with no gender difference.  Again, the more caffeine consumed, the less likely one was to develop PD.  Multiple other studies have shown similar results. Caffeine is hypothesized to protect dopaminergic neurons by antagonizing a neuronal receptor known as adenosine A2A (10).  Animal models have shown that chemicals which inhibit A2A can protect dopamine-containing neurons, and caffeine has been shown to improve some motor function in PD (11).  The effect on A2A receptors has led to a new class of investigational drugs, such as istradefylline.  Of note, caffeine is also a CNS stimulant which may help with daytime sleepiness, alertness, and cognitive function.

Curcumin is an active ingredient of turmeric. In volumes used in cooking it is non-toxic. It is able to cross the blood-brain barrier.  Curcumin binds to mutant α-synuclein (see the article in MPDN about alpha-synuclein), and thus may prevent aggregation and formation of Lewy bodies (12, 13).

Mucuna pruriens, the velvet bean, aka cowhage, has long been used in traditional Ayurvedic medicine for Parkinsonism.  In 1937, researchers isolated levodopa from the beans (14), though this was prior to a scientific understanding of the link between levodopa and Parkinson disease.  From 1978 to 2000 there were at least three open label studies (in which patients knew they were taking the study drug instead of taking a blinded pill, which might be treatment or placebo) (15, 16, 17).  These studies reported significant improvements in Parkinsonism for up to 20 weeks.  In 2004, London researchers demonstrated with eight PD patients that single doses of immediate release 50/200 mg carbidopa/levodopa were not as fast in onset of effect as a 30 g mucuna preparation (34.6 v 68.5 min), and this was consistent with time to peak blood concentration (18).  Average ON time was 37 minutes longer with 30 g mucuna than carbidopa/levodopa, and plasma concentrations 110% higher, implying the amount of levodopa was much higher in the mucuna preparation, essentially double the dose of the carbidopa/levodopa.  Each of the eight patients were trialed with mucuna, and two complained of mild nausea, whereas one dropped out of the study due to “short lasting vomiting.”  Acute side effects of levodopa are known to include nausea and vomiting.  This is the reason carbidopa is combined with the drug in tablets.  The authors suggested that domperidone might be combined with mucuna to prevent these side effects, and that larger randomized trials should be undertaken to evaluate mucuna.  Mucuna is unfortunately still not endorsed by such trials, and no standard measurement of levodopa derived from the bean is as yet available.

Fava beans, Vicia fava, aka the broad bean, have been known to contain levodopa since 1913 (19).  One open-label study comparing 250 g of cooked fava with 100 mg synthetic carbidopa/levodopa showed lower peak plasma concentrations after eating the beans, though the effect was similar to synthetic levodopa (20). Unlike mucuna, however, the concentration of levodopa in fava beans is very low, and therefore would require a large number of beans to reach a benefit.  Likewise, there is no standard for the amount of levodopa in fava beans, making dosing unpredictable.  In addition, some people with a genetic deficiency of glucose 6-phosphate dehydrogenase may react to eating fava beans with favism, a form of hemolytic anemia.

Finally, because levodopa, the active ingredient in carbidopa/levodopa (Sinemet), Duopa, and entacapone/carbidopa/levodopa (Stalevo) competes with amino acids for absorption in the GI tract, it should be taken one hour before, or two hours after, meals containing protein.   This creates certain problems with timing of medications and foods.  It is better to stick with a consistent time to dose meds, and plan meals around this.  Often, patients report they have stopped eating proteins, or moved all protein to the nighttime.  There are problems with this approach as well, because we need proteins, but the all at once approach may not be the right path.

I discussed this issue with Alison Fernald, RD, LD, CDE, of Mid Coast Center for Diabetes & Endocrinology, in Brunswick, Maine.  She notes that “an average person can only digest 25-30 grams of protein at a time, and a 140 pound person needs at least 50 grams of protein a day.   So, they have to break it up, and not eat it all at once.”  For those who need detailed instructions, Alison suggested a way to tackle this might be the protein redistribution diet, which will be included in this edition of MPDN.

 

REFERENCES

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