Feeding the mood: The role of macronutrients in depression prevention and treatment

Table 1 The outline of clinical researches on the relation between depression and carbohydrates

Ref.	Research type	Country	Population (P)	Intervention (I)	Comparison (C)	Duration	Assessment scales	Outcome	Limitations
de Castro[18], 1987	Observational study	United States	8 male and 30 female undergraduate students	-	-	9 days	7 point mood rating scales	High proportionate carbohydrate intake correlated with energy and negatively with depression	Observational study; small sample size; insufficient follow-up time; lack of sensitivity in assessment scales
Brezezinski et al[19], 1991	RCT	United States	17 women with premenstrual syndrome	D-fenfluramine	Placebo	The luteal phases of six menstrual cycles	Hamilton Rating Scale for Depression and its Addendum	D-fenfluramine decreased premenstrual Hamilton Rating Scale for Depression and Addendum scores by 62%. Kilocalorie, carbohydrate, and fat intakes suppressed	Small sample size
Cheatham et al[21], 2009	RCT	United States	42 overweight adults aged 35 ± 5 years	High-GL diet	Low-GL diet	6 months	POMS questionnaire	High-GL diet was associated with a poorer mood outcome for depression at the sub-clinical level compared to the low-GL diet	Small sample size; without investigating the energy contribution ratio of carbohydrates
Breymeyer et al[22], 2016	RCS	United States	82 healthy weight and overweight adults aged 18-45 years	High-GL diet	Low-GL diet	Two 28-days	POMS subscales; CES-D scale	High-GL diet resulted in a 38% higher score for depressive. Symptoms on the CES-D compared to the low-GL diet. The overweight/obese participants had 40% higher scores on the CES-D scale compared to healthy weight participants	Small sample size; insufficient follow-up time; without investigating the energy contribution ratio of carbohydrates
Gangwisch et al[23], 2015	Prospective cohort study	United States	87618 postmenopausal women aged 50-79 years	High-GI diet	Low-GI diet	3 years	the Burnam 8-item scale	High-GI diets could be a risk factor for depression in postmenopausal women	Without investigating the energy contribution ratio of carbohydrates
Gopinath et al[24], 2016	ross-sectional study	Australia	2334 participants aged 55+ years and 1952 participants aged 60+ years	Dietary information was collected using a semi-quantitative FFQ	-	-	Mental Health Index scale and antidepressant use and CES-D-10 scale	Dietary glycemic index is associated with the prevalence of depressive symptoms	Cross-sectional study; without investigating the energy contribution ratio of carbohydrates
Danilenko et al[25], 2008	RCT	Russia	22 unmedicated, DSM-IV-diagnosed depressed women with seasonal affective disorder aged 19-63 years	Morning carbohydrate-rich diet, evening carbohydrate-rich diet, or evening protein-rich diet (1600 kcal)	-	9 days	DSM-IV and SIGH-SAD score	None of the three nine-day diets had a selective mood-elevating effect upon winter depression	Small sample size; insufficient follow-up time; without investigating the energy contribution ratio of carbohydrates
Lemmens et al[26], 2011	RCS	The Netherlands	38 Caucasian subjects aged 18-51 years	A high-protein meal (En% P/C/F 65/5/30)	A high-carbohydrate meal (En% P/C/F 6/64/30)	4 times in a fasted state between 08: 00 and 9: 00 AM	POMS and STAI questionnaires	Consumption of the high-protein vs high-carbohydrate meal did not affect feelings of depression	Small sample size; insufficient follow-up time; without investigating the energy contribution ratio of carbohydrates
Brambilla et al[27], 2009	RCT	Italy	30 BED patients	Three treatment groups: A 1700-kcal diet, CBT, Sertraline and topiramate; or the same diet, CBT, sertraline; or nutritional counselling and CBT	-	6 months	the SCL-90-R and the PDQ-4-R	Group 2 patients improved on the SCL-90-R subitems ‘depression’	Small sample size
Wagner et al[28], 2023	RCT	United States	188 participants, aged 35–75 years	lifestyle intervention called EWS; EWS plus medication therapy management	Social services	12 months	Unclear	No health behavior changes were associated with improved depression	Lifestyle is difficult to control; many confounding factors
Endevelt et al[29], 2011	RCT	Israel	127 eligible participants aged < 75 years	Dietetic Intervention treatment	Non-randomized “untreated nutrition”	6 months	The geriatric depression Screening Scale	The dietetic intervention treatment group showed a significant improvement in intake of carbohydrates and protein, and showed significant improvement in cognitive function and depression score	The underlying condition is malnutrition, and dietary habits were not considered
Lynch et al[30], 2017	RCT	United States	211 Low-income African Americans	Females	Males	18 months	Incidence of depression	Males consumed more daily calories, but females consumed a greater proportion of carbohydrates. Females were found to have a higher incidence of severe depression compared with males	Dietary habits were not considered
Elsayed et al[31], 2022	RCT	Egypt	60 postmenopausal women aged 66.61 ± 4.80 years	Laser biostimulation and low-calorie diet (50%-60% carbohydrates, 15%-20% protein, 20%-35% fat, 500-1000 kcal/day)	Low-calorie diet	12 weeks	HAMD-17	Both experimental group and control group showed a reduction in the body weight, BMI, IR, inflammatory markers, and depression scores	Small sample size; insufficient follow-up time
Xi et al[32], 2017	RCT	China	60 patients with perimenopausal syndrome	Health education, diet supervision and exercise supervision twice a week	As normal	12 weeks	KMI score	The total KMI score and the individual KMI scores for depression were significantly lower in experimental group compared with the control group	Small sample size; Insufficient follow-up time

RCT: Randomized controlled trial; High-GL: High-glycemic load; Low-GL: Low-glycemic load ; POMS: Profile of Mood States; CES-D: Center for Epidemiological Studies - Depression; RCS: Cross-sectional study; FFQ: Food Frequency Questionnaire; STAI: State Trait Anxiety Inventory; BED: Binge-eating disorder; CBT: Cognitive-behavioral therapy; SCL-90-R: Symptoms Check List-90-Revised; PDQ-4-R: Personality Diagnostic Questionnaire-4-Revised; EWS: Eat, Walk, Sleep; HAMD: Hamilton Depression Rating Scale; BMI: Body mass index; IR: Insulin resistance; KMI: Kupperman Menopause Index.