Dietary Protein

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References

Bracco F, Malesani R, Saladini M, Battistin L. Protein redistribution diet and antiparkinsonian response to levodopa. Eur Neurol. 1991;31(2):68-71.
Abstract: Sixteen parkinsonian patients with daily fluctuations in the clinical response to levodopa have been placed on a redistribution protein diet. The diet was virtually protein-free until the evening meal and then unrestricted until bedtime. While on the redistribution protein diet, a group of patients (5 out of 16) had a clear and significant benefit from dietary therapy showing a definite reduction of diurnal motor performance fluctuations. In addition, all patients tended to show an improvement and a more constant response to levodopa treatment. A trial of redistribution protein diet appears a simple, reasonable, worthwhile approach to PD patients who begin to experience oscillating clinical response to levodopa treatment.

Carter JH, Nutt JG, Woodward WR, Hatcher LF, Trotman TL. Amount and distribution of dietary protein affects clinical response to levodopa in Parkinson's disease. Neurology. 1989 Apr;39(4):552-556.
Abstract: Reducing dietary protein improves the effectiveness of levodopa (LD) but the most effective distribution of a low-protein diet (0.8 g/kg) is unclear. We compared a 1.6 g/kg protein diet, a 0.8 g/kg diet with protein evenly distributed between meals, and a 0.8 g/kg diet with protein restricted to the evening meal in 5 parkinsonian patients with motor fluctuations. We monitored clinical response, plasma LD, and plasma large amino acids (LNAAs) hourly throughout the day. Mean "on" times were 51% (1.6 g/kg diet), 67% (0.8 g/kg evenly distributed), and 77% (0.8 g/kg restricted). Hourly averages of plasma LD did not differ between the diets. The mean plasma LNAAs were 732 nmol/ml (1.6 g/kg diet), 640 (0.8 g/kg distributed), and 542 (0.8 g/kg restricted), and the diurnal pattern reflected the distribution of protein intake. In conclusion, the amount and distribution of dietary protein affect clinical response to LD. These effects are not related to LD absorption but are explained by the variation in plasma LNAAs.

Eriksson T, Granerus AK, Linde A, Carlsson A. "On-off" phenomenon in Parkinson's disease. Neurology 1988;38:1245-1248.
Abstract: Administration of a low-protein diet to parkinsonian patients with "on-off" syndromes consistently increased the total daily time of "on" states when compared with a high-protein diet. The clinical effect of the low-protein diet may be due to a marked decrease in the plasma concentration of large neutral amino acids that compete with L-dopa for carrier-mediated transport into the brain.

Holt GA. Food and Drug Interactions. Chicago: Precept Press, 1998.

Juncos JL, Fabbrini G, Mouradian MM, Serrati C, Chase TN. Dietary influences on the antiparkinsonian response to levodopa. Arch Neurol. 1987 Oct;44(10):1003-1005.
Abstract: The ability of dietary factors to modify the response to levodopa was evaluated in six patients with idiopathic Parkinson's disease who manifested fluctuations in motor performance. The single oral administration of a high-protein formula substantially elevated plasma large neutral amino acid levels, and prematurely terminated the antiparkinsonian response to levodopa/carbidopa. In contrast, during oral or intravenous administration of levodopa, the ingestion of diets meeting the recommended daily allowance (RDA) for protein had no significant effect on plasma levodopa or large neutral amino acid levels or variance, nor on parkinsonian scores or variance. The results suggest that while protein intake in excess of the RDA can diminish the antiparkinsonian response to orally administered levodopa/carbidopa in patients with advanced disease, diets adhering to RDA protein guidelines have no clinically appreciable effect.

Kurlan R. Dietary therapy for motor fluctuations in Parkinson's disease . Arch Neurol. 1987;4:1119-1121. (Editorial)

Mena I and Cotzias GC. Protein intake and treatment of Parkinson's disease with levodopa. NEJM. 1975;292:181-184.

Molina JA, Jimenez-Jimenez FJ, Gomez P, Vargas C, Navarro JA, Orti-Pareja M, Gasalla T, Benito-Leon J, Bermejo F, Arenas J. Decreased cerebrospinal fluid levels of neutral and basic amino acids in patients with Parkinson's disease. J Neurol Sci 1997 Sep 10;150(2):123-127.
Abstract: We measured the CSF levels of 21, and the plasma levels of 26, amino acids in 31 patients with Parkinson's disease (PD) and in 45 matched controls. We used an ion-exchange chromatography method. When compared to controls, PD patients had lower CSF levels of taurine, alanine, valine, leucine, isoleucine, ethanolamine, citrulline, ornithine, lysine, histidine, arginine, and alpha-aminobutyric acid. PD patients not treated with levodopa or with dopamine agonists had higher CSF tyrosine and phenylalanine levels than those not treated with these drugs and also than controls. PD patients had higher plasma levels of phosphoserine, threonine, methionine, tyrosine, sarcosine and alpha-aminoadipic acid, and lower plasma levels of valine, leucine, and tryptophan, than controls. The CSF/plasma ratio of many of these amino acids was significantly lower in PD patients than those of controls, suggesting that PD patients might have a dysfunction in the transport of neutral and basic amino acids across the blood-brain barrier.

Nesbitt LT Jr. Minimizing complications from systemic glucocorticosteroid use. Dermatol Clin 1995 Oct;13(4):925-939. (Review)
Abstract: For proper use of systemic GCS, a basic knowledge of the normal HPA axis, as well as knowledge of the pharmacology, clinical usage guidelines, and adverse reactions of these agents is imperative. Both short-term (acute) and long-term side effects should be well known by the physician. The pros and cons of oral and parenteral therapy for various disorders and in various situations should be recognized. For long-term therapy, an intermediate-acting agent such as prednisone in single, early morning doses is most commonly used to minimize suppression of the HPA axis. Alternate-morning doses produce even less suppression if the disease process will respond. A through patient history, including general medical history and medications the patient is taking, is important to anticipate any potential problems. Weight and blood pressure should be checked initially and every 1 to 3 months thereafter. Blood glucose, electrolytes, and lipid studies, including triglycerides, should be done approximately every 6 months. An ophthalmology examination should be performed every year, and stool examination for occult blood and chest radiography can be obtained as indicated. Bone density studies might be necessary in patients who are at high risk for osteoporosis. Specific acute situations may dictate other studies. The patient on long-term GCS should be kept as active as possible, as mild-to-moderate exercise helps prevent certain side effects, such as osteoporosis. The dose of oral GCS is best given with food to prevent gastrointestinal irritation, and agents to decrease gastric acidity might be needed in certain situations. Exposure to infections should be prevented, where possible, and treatment initiated at the first sign of systemic or cutaneous infection. Pain should be evaluated early, especially abdominal pain or bone pain; MRI is indicated if aseptic necrosis of bone is suspected. Both trauma and severe sun exposure should be avoided. Consultation with other specialists is strongly recommended when the situation dictates. Diet is one of the most important strategies to minimize side effects from long-term GCS therapy. Vegetable protein should be increased in the diet, and fats and carbohydrates limited. Adequate calcium is imperative, and calcium supplementation is recommended for high-risk osteoporosis patients. Small amounts of vitamin D may be necessary to increase absorption of calcium. Restriction of sodium is also important, as is maintainance of dietary potassium. Supplemental potassium may be necessary in some patients, and a thiazide diuretic might be useful in patients with hypertension, edema, or osteoporosis. Vitamin C can be given to promote wound healing. A good doctor-patient relationship is important in managing the patient on long-term GCS. The patient must return for regular visits and be encouraged to promptly report any adverse reactions to the physician. If these criteria are maintained and the strategies noted previously are followed, problems from long-term therapy with GCS will be minimized.

Nutt JG, Woodward WR, Hammerstad JP, Carter JH, Anderson JL. The "on-off" phenomenon in Parkinson's disease. N Engl J Med 1984 Feb 23;310(8):483-488.
Abstract: To determine whether the oscillating clinical response to levodopa in Parkinson's disease (the "on-off" phenomenon) reflects fluctuations in absorption and transport of the drug, we investigated this phenomenon in nine patients with an oscillating motor state. We studied the response to continuous infusion of levodopa and the effects of meals on the plasma levodopa concentrations and on the clinical response during oral and intravenous administration of the drug. Meals reduced peak plasma levodopa concentrations by 29 per cent and delayed absorption by 34 minutes. Bypassing absorption by constant infusion of the drug produced a stable clinical state lasting for 12 hours in all of six patients and for up to 36 hours in some. High-protein meals or oral phenylalanine, leucine, or isoleucine (100 mg per kilogram of body weight) reversed the therapeutic effect of infused levodopa without reducing plasma levodopa concentrations. Glycine and lysine at identical doses had no effect. We conclude that interference with absorption of levodopa by food and by competition between large neutral amino acids and levodopa for transport from plasma to the brain may be partly responsible for the fluctuating clinical response in patients with Parkinson's disease.

Pincus JH, Barry KM. Influence of dietary protein on motor fluctuations in Parkinson's disease. Arch Neurol. 1987;44:270-272.
Abstract: On a nearly zero protein diet, 11 patients with Parkinson's disease with the "on-off" effect demonstrated great sensitivity to levodopa (L-dopa)-carbidopa and reduced fluctuations. Eight patients required a 41% reduction in total L-dopa dosage and discontinuation of all adjuvant therapy to reduce the preponderance of chorea. On a high-protein diet, all patients were immobilized by bradykinesia for most of the day. A low-protein dietary regimen during the daytime offers an important technique for the control of fluctuations in patients with Parkinson's disease who are receiving L-dopa-carbidopa.

Pincus JH, Barry KM. Plasma levels of amino acids correlated with motor fluctuations in Parkinsonism. Arch Neurol. 1987;44:1006-1009.
Abstract: Seven patients with Parkinson's disease who experienced severe motor fluctuations in response to levodopa were studied in detail with relation to the effect of dietary protein on their motor function. The levodopa dose for each patient was not changed during the period of study, and no other antiparkinsonian drugs were used. Regular and high-protein diets resulted in a marked elevation in the plasma concentrations of large neutral amino acids (LNAAs) that are known to compete with levodopa for transport across the blood-brain barrier. Despite elevated plasma levodopa levels, all patients with elevated LNAA levels experienced parkinsonian symptoms. When the amino acid level dropped while plasma levodopa levels were elevated, patients experienced relief of these symptoms. On a low-protein diet, LNAA levels remained low and all patients were consistently dyskinetic throughout the day, even though the mean plasma levodopa levels were somewhat lower than when the patients consumed a high-protein diet. A redistribution diet that is virtually protein free until supper and then unrestricted until bedtime is tolerated by patients because this simple manipulation permits near-normal daytime motor function.

Pincus JH, Barry KM. Dietary method for reducing fluctuation in Parkinson's disease. Yale J Biol Med. 1987 Mar-Apr;60(2):133-137.
Abstract: Motor fluctuations and non-response to carbidopa-levodopa (Sinemet) therapy are major problems in the long-term management of Parkinson's disease. Levodopa manipulation, addition of adjuvants, and drug holidays are often unsuccessful. Others have shown that the clinical state of stabilized Parkinsonians can be reversed with intravenous administration of large neutral amino acids. Reasoning that dietary protein might precipitate motor oscillations and non-response, a low-protein daytime diet (7 g) was offered to fifteen patients. Eighty-six percent of this sample demonstrated immediate sensitivity to Sinemet. While on a low-protein diet, patients' clinical function was predominantly choreatic. Eight patients required a 10-60 percent reduction in their daily levodopa dose in order to minimize this choreatic tendency. Discontinuation of adjuvants did not compromise motor independence. Conversely, while on a high-protein diet (160 g), patients were predominantly immobile with markedly elevated plasma amino acid and levodopa levels. Consequently, elimination of dietary protein from breakfast and lunch can offer an effective and easily modified method for the amelioration of motor fluctuations and non-response to Sinemet in Parkinson's disease during working hours.

Pincus JH, Barry KM. Protein redistribution diet restores motor function in patients with dopa-resistant "off" periods. Neurology. 1988;38:481-483.
Abstract: Sixteen parkinsonians with acquired drug-resistant "off" periods without dyskinesia were placed on a diet in which virtually all protein was concentrated in the evening meal. Restoration of sensitivity to levodopa resulted in 88%. Ten patients (62%) have continued to comply with the diet for 7 months (mean). Two patients were studied in detail. Immobility correlated with elevated plasma levels of large neutral amino acids (LNAA), normality with low LNAA.

Pronsky, Zaneta. Powers and Moore's Food-Medications Interactions. Ninth Edition. Food-Medication Interactions. Pottstown, PA, 1991.

Riley D, Lang AE. Practical application of a low-protein diet for Parkinson's disease. Neurology. 1988;38:1026-1031.
Abstract: Thirty-eight patients with Parkinson's disease were treated with a protein-restricted diet in addition to their usual drug regime. Patients who had failed to obtain a significant response to levodopa previously did not benefit. Sixty percent of those with fluctuations in response to levodopa improved, primarily obtaining an increase in the ratio of "on" to "off" hours. Benefit was always noted within a week of diet initiation. The diet was well tolerated with a low incidence of side effects, which could usually be reversed by a reduction in levodopa dosage. A low-protein diet is a simple adjunct to levodopa therapy that can be readily instituted on an outpatient basis. It may improve even those patients with fluctuations who have failed to obtain optimal benefit from all forms of manipulation of the dosage schedule of levodopa or the addition of newer ancillary medications.

Robinson C, Weigly E. Basic Nutrition and Diet Therapy. New York: MacMillan, 1984.

Roe DA. Diet and Drug Interactions. New York: Van Nostrand Reinhold, 1989.

Roe DA. Drug-induced Nutritional Deficiencies. 2nd ed. Westport, CT: Avi Publishing, 1985.

Roe DA. Risk factors in drug-induced nutritional deficiencies. In: Roe DA, Campbell T, eds. Drugs and Nutrients: The Interactive Effects. New York: Marcel Decker, 1984: 505-523.

Sanchis G, Mena MA, Martin del Rio R, Morales B, Casarejo MJ, de Yebenes MJ, Tabernero C, Jimenez A, de Yebenes JG. [Effect of a controlled low-protein diet on the pharmacological response to levodopa and on the plasma levels of L-dopa and amino acids in patients with Parkinson's disease]. Arch Neurobiol (Madr). 1991 Nov-Dec;54(6):296-302. [Article in Spanish]
Abstract: Levodopa is the treatment of choice in Parkinson's disease, but a high percentage of patients develop complications in the response, including fluctuations, after some years of treatment. Although the origin of fluctuations is unknown, these could be, at least partly, attributed to pharmacokinetic factors. Aromatic aminoacids interfere in the absorption and brain penetration of levodopa, and lowering protein intake improves the quality of the response. The continuation of a low-protein diet is difficult for some patients. In this way, to know if these diet effects are noticeable in an acute period would be interesting, in order to select groups of patients who were susceptible to improve with this treatment. In this report we have studied the acute effect of a low protein diet on the pharmacological response to levodopa, and the plasmatic levels of L-Dopa, 3-OM-Dopa and large neutral aminoacids. Protein restriction improves clinical response to levodopa, although the mechanisms of this improvement remain unknown.

Stenbaek O, Myhre E, Rugstad HE, Arnold E, Hansen T.  The absorption and excretion of methyldopa ingested concomitantly with amino acids or food rich in protein. Acta Pharmacol Toxicol (Copenh). 1982 Mar;50(3):225-229.
Abstract: Absorption and urinary excretion of 2-14C-L-alpha-methyldopa (alpha MD) were investigated in 5 healthy human volunteers. The drug was administered alone, with a mixture of amino acids and with a meal consisting of roast beef. The radioactivity in plasma and urine was not decreased significantly by either treatment, and it was concluded that the overall absorption of the drug was virtually unchanged. The amount of unconjugated alpha MD in plasma and urine, however, was significantly decreased following administration of the drug with roast beef. As the acid labile conjugates of alpha MD were practically unchanged an increased biotransformation to other metabolites owing to the protein rich meal was suggested more probable than competition between alpha MD and amino acids in the specific transport systems.

Sved AF, Goldberg IM, Fernstrom JD. Dietary protein intake influences the antihypertensive potency of methyldopa in spontaneously hypertensive rats. J Pharmacol Exp Ther. 1980 Jul;214(1):147-151.
Abstract: When spontaneously hypertensive rats consumed a single meal before receiving methyldopa (MD), the increase in brain MD levels and the blood pressure reduction varied inversely with the meal's protein content. MD injection elicited a greater reduction in blood pressure (and a larger rise in brain MD) in spontaneously hypertensive rats consuming a protein-free meal than in fasting animals; it induced a smaller fall in blood pressure (and a smaller increase in brain MD) in spontaneously hypertensive rats ingesting a protein-containing meal than in fasting animals. This effect may depend on the large neutral amino acids contained in protein. Ingestion of a food identical in amino acid content to 18% casein, but containing an amino acid mixture instead of protein, also blunted the MD-induced fall in blood pressure. However, consumption of a similar diet, lacking the large neutral amino acids (but not other amino acids), elicited an MD-induced blood pressure reduction similar to that caused by ingesting a protein-free diet. The combined effects of meal consumption and MD injection on brain MD and blood pressure correlated significantly with the serum ration of MD to the sum of the natural large neutral amino acids and not with serum MD alone. Similar effects were also noted with chronic dietary and MD treatments. Thus, dietary protein content can influence significantly the potency of a clinically important amino acid drug that acts within the brain.


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