Synergistic Interplay between Curcumin and Polyphenol-Rich Foods in the Mediterranean Diet: Therapeutic Prospects for Neurofibromatosis 1 Patients

Abstract

Neurofibromas are the hallmark lesions in Neurofibromatosis 1 (NF1); these tumors are classified as cutaneous, subcutaneous and plexiform. In contrast to cutaneous and subcutaneous neurofibromas, plexiform neurofibromas can grow quickly and progress to malignancy. Curcumin, a turmeric-derived polyphenol, has been shown to interact with several molecular targets implicated in carcinogenesis. Here, we describe the impact of different dietary patterns, namely Mediterranean diet (MedDiet) compared to the Western diet (WesDiet), both with or without curcumin, on NF1 patients' health. After six months, patients adopting a traditional MedDiet enriched with 1200 mg curcumin per day (MedDietCurcumin) presented a significant reduction in the number and volume of cutaneous neurofibromas; these results were confirmed in subsequent evaluations. Notably, in one patient, a large cranial plexiform neurofibroma exhibited a reduction in volume (28%) confirmed by Magnetic Resonance Imaging. Conversely, neither unenriched MedDiet nor WesDiet enriched with curcumin exhibited any significant positive effect. We hypothesize that the combination of a polyphenol-rich Mediterranean diet and curcumin was responsible for the beneficial effect observed on NF1. This is, to the best of our knowledge, the first experience with curcumin supplementation in NF1 patients. Our report suggests that an integrated nutritional approach may effectively aid in the management of NF1.

Keywords: curcumin; diet; neurofibromas; neurofibromatosis 1; polyphenols.

Figure 1

Neurofibroma resection specimen. (a,b) Spindle “wavy” cells in a matrix of fine fibrillary collagen; neurofibromatous tissue merges with mature fat and ectatic vessels (Hematoxylin-eosin, Magnification 10×); (c,d) Spindle cell nuclei in a fine fibrillary matrix, at a greater magnification (Hematoxylin-Eosin, Magnification 40×); (e) S100 immunohistochemical test confirmed the neurogenic origin of the lesion (Magnification 20×); (f) Actin-hhf35 immunohistochemical test excluded the myogenic origin of the lesion (note that only perivascular splindle smooth cells were reactive) (Magnification 20×); (g) Proliferation index by Ki67 immunohistochemical test was almost negative (Magnification 20×).

Figure 1

Neurofibroma resection specimen. (a,b) Spindle “wavy” cells in a matrix of fine fibrillary collagen; neurofibromatous tissue merges with mature fat and ectatic vessels (Hematoxylin-eosin, Magnification 10×); (c,d) Spindle cell nuclei in a fine fibrillary matrix, at a greater magnification (Hematoxylin-Eosin, Magnification 40×); (e) S100 immunohistochemical test confirmed the neurogenic origin of the lesion (Magnification 20×); (f) Actin-hhf35 immunohistochemical test excluded the myogenic origin of the lesion (note that only perivascular splindle smooth cells were reactive) (Magnification 20×); (g) Proliferation index by Ki67 immunohistochemical test was almost negative (Magnification 20×).

Figure 2

Right lateral view of thoracic region in patient 9: serial clinical assessment. (a,c) The large red square outlines the sampled area at baseline (a) and after six months of MedDietCurcumin (c); the small red square indicates the most prominent neurofibroma in the area, which was removed immediately after baseline observation for histological examination; (b,d) Digital re-elaboration of the images in A and C to facilitate manual counting of cutaneous neurofibromas; (e) Bar chart representing the number of neurofibromas in the sampled area at baseline and at six-month follow-up.

Figure 2

Right lateral view of thoracic region in patient 9: serial clinical assessment. (a,c) The large red square outlines the sampled area at baseline (a) and after six months of MedDietCurcumin (c); the small red square indicates the most prominent neurofibroma in the area, which was removed immediately after baseline observation for histological examination; (b,d) Digital re-elaboration of the images in A and C to facilitate manual counting of cutaneous neurofibromas; (e) Bar chart representing the number of neurofibromas in the sampled area at baseline and at six-month follow-up.

Figure 3

Left breast of case 10: serial clinical assessment. (a,c). Clinical observation at baseline (a) and after six months of MedDietCurcumin (c); the red border is provided for reference; (b,d) Digital reworking of the image in A and C to facilitate manual counting of cutaneous neurofibromas; (e) Bar chart representing the number of neurofibromas in the sampled area at baseline and at six-month follow-up.

Figure 3

Left breast of case 10: serial clinical assessment. (a,c). Clinical observation at baseline (a) and after six months of MedDietCurcumin (c); the red border is provided for reference; (b,d) Digital reworking of the image in A and C to facilitate manual counting of cutaneous neurofibromas; (e) Bar chart representing the number of neurofibromas in the sampled area at baseline and at six-month follow-up.

Figure 4

Serial MR imaging assessment of case 11. (a) Coronal FLAIR-weighted and (c,e) Axial TSE T2-weighted images of the left facial plexiform neurofibroma at baseline; (b) Coronal FLAIR-weighted and (d,f) Axial TSE T2-weighted images after six months of MedDietCurcumin. After six months there was a significant reduction especially in the hyperintense parts of the lesion, as indicated by arrows in (c,d). In (e,f) a green border contours the area used for volume measurement.

Figure 5

Plasma levels of curcuminoids. HPLC analysis of enzymatically hydrolyzed plasma samples. For each sample, three different experiments were conducted and the results expressed as the mean of the values obtained (mean ± SD). Statistically significant variations: ** p < 0.01 4 months diet versus 2 months diet; ## p < 0.01 6 months diet versus 2 months diet; ### p < 0.001 6 months diet versus 2 months diet.