Supplementation with a highly concentrated docosahexaenoic acid plus xanthophyll carotenoid multivitamin in nonproliferative diabetic retinopathy: prospective controlled study of macular function by fundus microperimetry

Figures & data

Figure 1 Effects of DHA/ω-3 fatty acids and lutein/zeaxanthin on pathways leading to DR.

Abbreviations: DHA, docosahexaenoic acid; DR, diabetic retinopathy.

Table 1 Composition of Brudyretina 1.5 g (Brudy Lab S.L.), per capsule

Composition	Per capsule	Recommended daily amount (%)	Per 3 capsules	Recommended daily amount (%)
Concentrated oil in ω-3 fatty acids	500 mg		1,500 mg
TG-DHA 70%	350 mg	–	1,050 mg	–
EPA 8.5%	42.5 mg	–	127 mg	–
DPA 6%	30 mg	–	90 mg	–
Xanthophylls
Lutein	3 mg	–	9 mg	–
Zeaxanthin	0.3 mg	–	0.9 mg	–
Glutathione	2 mg	–	6 mg	–
Vitamins
Vitamin B1 (thiamine)	0.37 mg	33	1.1 mg	100
Vitamin B2 (rivoflavin)	0.47 mg	33	1.4 mg	100
Vitamin B3 (niacin/niacinamide)	5.3 mg NE	33	16 mg NE	100
Vitamin B6 (pyridoxine)	0.47 mg	33	1.4 mg	100
Vitamin B9 (folic acid)	66.7 µg	33	200 µg	100
Vitamin B12 (cobalamin)	0.83 µg	33	2.5 µg	100
Vitamin C (ascorbic acid)	26.7 mg	33	80 mg	100
Vitamin E (d-α-tocopherol)	4 mg α-TE	33	12 mg α-TE	100
Essential trace elements
Zinc	1.66 mg	16.66	5 mg	50
Cooper	0.16 mg	16.66	0.5 mg	50
Selenium	9.16 µg	16.66	27.5 µg	50
Magnesium	0.33 mg	16.66	1 mg	50

Note: Patients in the supplementation group took 3 capsules a day.

Abbreviations: TG-DHA, triglyceride-bound DHA; DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid; DPA, docosapentaenoic acid; NE, niacid equivalent; TE, tocopherol equivalent.

Table 2 Demographics and clinical characteristics of the study population

Data	DHA group (n=12)	Controls (n=12)
Gender
Men	9	8
Women	3	4
Age, years, mean (range)	58 (36–77)	63.3 (46–79)
Overweight, BMI ≥25 kg/m^2	3	4
Current smokers	0	3
Comorbidities
Metabolic syndrome	2	2
Renal dysfunction	4	3
Hypertension	9	10
Dyslipidemia	5	6
Cardiac diseases	3	3
Chronic liver dysfunction	1	0
Peripheral artery disease	1	0
Obstructive sleep apnea	2	2

Note: Data expressed as number of patients unless otherwise stated.

Abbreviations: DHA, docosahexaenoic acid; BMI, body mass index.

Figure 2 Changes of macular sensitivity (A) and macular integrity index (B) in the 2 study groups at 90 days as compared with baseline (n=24 eyes in each study group).

Notes: Macular integrity index: P=0.002 as compared with baseline, P=0.03 as compared with 1.5 months.

Table 3 Changes of macular function variables, visual acuity, CSMT, biochemical markers, and vision-related quality of life from baseline to 90 days after treatment with DHA supplementation as compared with controls

Study variables	Baseline		45 Days		90 Days		P-value		P-value DHA vs controls
	DHA group (12 subjects, 24 eyes)	Controls (12 subjects, 24 eyes)	DHA group (12 subjects, 24 eyes)	Controls (12 subjects, 24 eyes)	DHA group (12 subjects, 24 eyes)	Controls (12 subjects, 24 eyes)	DHA group (12 subjects, 24 eyes)	Controls (12 subjects, 24 eyes)
Functional vision measures
Macular sensitivity, dB	25.9±2.4a	24.8±3.6	26.4±2.6	25.1±3.9	27.3±2.3a	25.8±2.6	<0.030a	0.179	<0.19
Macular integrity index	71.2±33.2a	73.1±35.0	63.5±36.4b	72.1±33.7	51.6±35.9^a<b	71.8±35.7	0.002;a 0.03b	1	<0.05
BCVA (ETDRS letters)	0.70±0.32	0.66±0.26	0.67±0.35	0.67±0.26	0.76±0.31	0.72±0.27	0.334	0.346	0.987
NEI-VFQ-25 score	87.0±9.6	77.2±16.3	88.2±7.8	76.3±15.3	91.4±5.3	73.6±20.6	0.22	0.49	<0.037
Structural retina measures
CSMT, µm	281.9±20.9	295.1±50.5	280.0±22.8	298.3±53.3	279.2±23.5	295.8±43.3	0.932	1	0.181
Biochemical measures
DHA erythrocyte membrane (% total fatty acids)	3.9±0.6a	3.5±0.3	ND	ND	5.6±0.8a	3.6±1.2	<0.001a	0.778	<0.001
Plasma TAC, µM Cu-reducing equivalent	121.3±33.4a	117.7±22.2	ND	ND	162.8±40.9a	129.1±28.4	<0.001a	<0.011	<0.001
Plasma IL-6, pg/mL	4.7±1.4a	2.9±1.4	ND	ND	3.2±1.0a	3.2±1.1	<0.005a	0.510	<0.015

Notes: Data are expressed as mean ± standard deviation.

a P-values for pairwise comparisons of data.

b P-values for pairwise comparisons of data.

Abbreviations: DHA, docosahexaenoic acid; BCVA, best-corrected visual acuity; NEI-VFQ-25, National Eye Institute Visual Function Questionnaire, near activities subscale score; CSMT, central subfield macular thickness; TAC, total antioxidant capacity; IL-6, interleukin 6; ND, not determined.

Figure 3 Changes of BCVA (ETDRs letters) (A) and CSMT (B) in the 2 study groups at 90 days as compared with baseline.

Note: Data expressed as mean values and 95% confidence interval (n=24 eyes in each study group).
Abbreviations: OCT, optical coherence tomography; BCVA, best-corrected visual acuity; ETDRS, Early Treatment Diabetic Retinopathy Study; CSMT, central subfield macular thickness.

Figure 4 Changes of plasma TAC (A) and plasma levels of IL-6 (B) the study groups at 90 days as compared with baseline (n=12 patients in each study group).

Abbreviation: TAC, total antioxidant capacity.

Figure 5 Changes in vision-related quality of life in the 2 study groups at 45 and 90 days as compared with baseline, with a clear trend toward improvement in the DHA supplementation group and toward worsening in the control group.

Note: Data expressed as mean values and 95% confidence interval (n=12 patients in each study group).
Abbreviations: NEI-VFQ-25, National Eye Institute Visual Function Questionnaire, near activities subscale score; DHA, docosahexaenoic acid.