Comments on the paper "High doses of riboflavin and the elimination of dietary red meat promote the recovery of some motor functions in Parkinson's disease patients. C.G. Coimbraand V.B.C. Junqueira. Brazilian Journal of Medical and Biological Research, 36: 1409-1417, 2003"

Parkinson's disease; Riboflavin; FAD; Glutathione; Iron; Hemin

Braz J Med Biol Res, September 2004, Volume 37(9) 1297-1299 (Short Communication)

Comments on the paper

"High doses of riboflavin and the elimination of dietary red meat promote the recovery of some motor functions in Parkinson's disease patients. C.G. Coimbra and V.B.C. Junqueira. Brazilian Journal of Medical and Biological Research , 36: 1409-1417, 2003" ( to see Coimbra full paper click here )

( to see C.G. Coimbra and V.B.C. Junqueira response to the comments click here )

H.B. Ferraz¹, E.A.B. Quagliato², C.R.M. Rieder³, D.J. Silva⁴, H.A.G. Teive⁵, E.R. Barbosa⁶, F. Cardoso⁷, J.C.P. Limongi⁶, J.M.F. Bezerra⁸, L.A.F. Andrade⁹, N. Allam¹⁰, R.C.P. Prado¹¹ and V. Tomas¹²

¹Setor de Distúrbios do Movimento, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brasil

²Ambulatório de Distúrbios do Movimento,Departamento de Neurologia, Universidade Estadual de Campinas, Campinas, SP, Brasil

³Setor de Distúrbios do Movimento, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brasil

⁴Unidade de Parkinson e Desordens do Movimento, Centro de Transtornos do Movimento, Hospital das Clínicas, Universidade Federal de Goiás, Goiânia, GO, Brasil

⁵Setor de Distúrbios do Movimento, Hospital das Clínicas, Universidade Federal do Paraná, Curitiba, PR, Brasil

⁶Setor de Distúrbios do Movimento, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil

⁷Setor de Distúrbios do Movimento, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil

⁸Universidade Estadual do Rio de Janeiro, and Ambulatório de Distúrbios do Movimento, Hospital do Servidor Público Estadual, Rio de Janeiro, RJ, Brasil

⁹Hospital do Servidor Público Estadual de São Paulo, São Paulo, SP, Brasil

¹⁰Ambulatório de Distúrbios do Movimento, Hospital de Base do Distrito Federal, Brasília, DF, Brasil

¹¹Ambulatório de Parkinson e Distúrbios do Movimento, Hospital Universitário, Universidade Federal de Sergipe, Aracaju, SE, Brasil

¹²Ambulatório de Distúrbios do Movimento, Hospital das Clínicas, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil

^{Comments on the paper}

References

^{Correspondence and Footnotes}

Key words: Parkinson's disease, Riboflavin, FAD, Glutathione, Iron, Hemin

Comments on the paper

We are being questioned by our colleagues and patients about a paper published in the Brazilian Journal of Medical and Biological Research by Coimbra and Junqueira (1). The authors analyzed the effect of oral vitamin B2 (riboflavin) and the dietary restriction of red meat in 31 patients with Parkinson's disease (PD). The authors found that the dietary intervention and the prescription of riboflavin induced a significant improvement in the clinical condition of their patients and stated that this regimen should be recommended to PD patients. In our opinion, this article has many methodological problems, which were surprisingly neglected by this peer-reviewed journal.

The authors made an open-label experiment not controlled with placebo. They selected the patients, evaluated them, recommended the dietary restriction, and prescribed vitamin B2. At the end of a 6-month period the authors themselves reevaluated the patients and concluded for an improvement on motor scales. This type of non-blinded experiment can lead to biased estimated differences between pre- and post-therapeutic intervention. In addition, there would have been no ethical problems if placebo tablets had been administered to some of the patients since the conventional treatment of PD could have been maintained in both groups.

Patients who were instructed to refrain from red meat should be warned about receiving another source of protein to prevent malnutrition. It is well known that protein, especially neutral amino acids, in the small intestine and blood stream competes with the intestinal absorption and with the brain penetration of levodopa (2,3). Thus, it may be speculated that the putative motor improvement found in PD patients under dietary protein restriction could be attributed to the increased bioavailability of levodopa in the brain. To minimize this bias, the authors should have recommended to their patients not to take their oral levodopa doses together with protein intake in the evaluation prior to vitamin B2 administration and to dietary intervention.

The authors did not report in their paper the reasons why 12 patients dropped out of the study. We do not know if there were adverse effects or if the patients experienced worsening of their clinical status. Also, the authors only analyzed the outcomes of the 19 patients who remained on the dietary and vitamin B2 regimen. It is highly recommended in good scientific practice to analyze the outcomes including the data for patients who dropped out (intention-to-treat analysis).

Serum vitamin B2 levels in PD patients were compared with those of 10 patients with "dementia". We know that "dementia" is too generic a term and the authors do not report the etiology of the disease in the 10 "demented" patients, which could obviously interfere with the serum measurements of vitamin B2. There are different criteria to establish the diagnosis of dementia and the authors did not disclose their criteria. Patients with memory complaints or even with established dementia usually take oral multivitamin preparations and this could also interfere with the blood measurements, i.e., demented patients could in fact have high vitamin B2 levels and PD patients could have normal levels. The authors do not mention if there is a study reporting the normal range of blood vitamin B2 levels in a Brazilian population. As far as we know, such a study has not been done.

The main outcome measure used was a new motor scale created by the authors of the paper. They made a modification to the Hoehn and Yahr scale, which is not used to rate motor performance but to rate PD patients at five different stages. Motor performance is best evaluated by the Unified Parkinson's Disease Rating Scale, which is a validated and widely used scale (4). If the authors wished to use their own scale they should have validated it before collecting the data.

The authors do not report if they evaluated the patients during the "off" or "on" state of the levodopa effect. Fluctuation of motor performance is observed in more than 50% of the patients after five years of treatment and an uncontrolled motor status evaluation of the patients at baseline and after 6 months would be an important source of bias.

Previous epidemiological studies with case-control methodology have failed to demonstrate any correlation between life-style or food habits and Parkinson's disease (5-7). There is no scientific evidence correlating vitamin B2 or protein consumption and Parkinson's disease in previous well-controlled studies (8,9) analyzing a much higher number of individuals than the 31 patients studied by Coimbra and Junqueira (1).

In summary, there is no current scientific evidence that vitamin B2 consumption and dietary red meat restriction can benefit patients with Parkinson's disease.

H.B. Ferraz, Setor de Distúrbios do Movimento, EPM, UNIFESP, Rua Botucatu, 740, 04023-900, São Paulo, SP, Brasil.

Received May 17, 2004. Accepted July 14, 2004.

• 1. Coimbra CG & Junqueira VBC (2003). High doses of riboflavin and the elimination of dietary red meat promote the recovery of some motor functions in Parkinson's disease patients. Brazilian Journal of Medical and Biological Research, 36: 1409-1417.
• 2. Pare S, Burr SI & Ross SE (1992). Effect of daytime protein restriction on nutrient intakes of free-living Parkinson's disease patients. American Journal of Clinical Nutrition, 55: 701-707.
• 3. Simon N, Gantcheva R, Bruguerolle B & Viallet F (2004). The effects of a normal protein diet on levodopa plasma kinetics in advanced Parkinson's disease. Parkinsonism and Related Disorders, 10: 137-142.
• 4. Fahn S, Elton RL & Members of the UPDRS Development Committee (1987). Unified Parkinson's Disease Rating Scale. In: Fahn S, Marsden CD, Calne DB & Goldstein M (Editors), Recent Developments in Parkinson's Disease Vol. 2. MacMillan Health Care Information, Florham Park, NJ, USA, 153-164.
• 5. Baldereschi M, DiCarlo A, Vanni P, Ghetti A, Carbonin P, Amaducci L & Inzitani D (2003). Italian longitudinal study on aging working group. Life-style related risk factors for Parkinson's disease: a populational study. Acta Neurologica Scandinavica, 108: 239-244.
• 6. Tsai CH, Lo SK, See LC, Chen HZ, Chen RS, Weng YH, Chang FC & Lu CS (2002). Environmental risk factors of young onset Parkinson's disease. Clinical Neurology and Neurosurgery, 104: 328-333.
• 7. Tanner CM (1994). Epidemiological clues to the cause of Parkinson's disease. In: Marsden CD & Fahn S (Editors), Movement Disorders 3 Butterworth-Heinemann, Oxford, UK, 124-146.
• 8. Golbe LI, Farrel TM & Davis PH (1988). Case-control study of early life dietary factors in Parkinson's disease. Archives of Neurology, 45: 350-353.
• 9. Abbot RD, Ross GW, White CR, Sanderson WT, Burchfiel CM, Kashon M, Sharp DS, Masaki KH, Curb JD & Petrovitch H (2003). Environment, life-style, and physical precursors of clinical Parkinson's disease: recent findings from the Honolulu-Asia aging study. Journal of Neurology, 250 (Suppl 3): III-30-III-39.

Correspondence and Footnotes

Publication Dates

• Publication in this collection
  16 Sept 2004
• Date of issue
  Sept 2004

History

• Received
  17 May 2004
• Accepted
  14 July 2004