Mulberry has many health benefits including glucose-lowering effects as mentioned in a previous blog on the Health Benefits of Mulberry. Here are a few newly published papers that specifically examined the hypoglycemic effects of mulberry in humans
Glucose tolerance is influenced by our internal clock and is worse in the evening. To prevent diabetes, it is important to consider the timing of eating functional ingredients. One study looked at how the timing of taking mulberry leaf extract affects blood sugar levels after meals in young adults (1).
Twelve young adults participated in four different trials. Blood samples were taken before eating and at 30, 60, 120, and 180 minutes after eating a mixed meal with 6 mg of mulberry leaf extract or a placebo. The trials included:
1. Morning placebo trial (8:00 AM; MP trial),
2. Evening placebo trial (6:00 PM; EP trial),
3. Morning mulberry leaf extract trial (8:00 AM; MM trial),
4. Evening mulberry leaf extract trial (6:00 PM; EM trial) (1).
Results showed:
- The increase in blood glucose levels (iAUC) in the evening mulberry leaf extract trial (EM) was significantly lower than in the evening placebo trial (EP) (p = 0.010).
- Blood glucose levels 120 minutes after the meal were significantly lower in the evening mulberry leaf extract trial (EM) compared to the evening placebo trial (EP) (p = 0.006).
- Insulin levels 120 minutes after the meal were significantly lower in the morning mulberry leaf extract trial (MM) compared to the morning placebo trial (MP) (p = 0.034).
- Insulin levels 180 minutes after the meal were significantly lower in the evening mulberry leaf extract trial (EM) trial compared to the evening placebo trial (EP) (p = 0.034) (1).
Increasing evidence has shown an association between an evening chronotype (i.e., young and middle-aged population) and an increased risk of obesity, cardiovascular disease, and diabetes. In general, the evening chronotype is associated with larger meals later in the day and delayed food intake due to a later awaking time. Although dinner time varied between 17:00 to 24:00 in previous studies, dinner caused a higher postprandial glucose response than that caused by breakfast.
This study confirmed that glucose tolerance is worse at night, which is caused by insulin sensitivity and functions regulated by circadian rhythms. The main finding was that acute intake of mulberry leaf extract in the evening, but not in the morning, significantly suppressed the increase in blood glucose levels (iAUC) and postprandial glucose concentrations. Thus, the effectiveness of mulberry leaf extract in lowering glucose levels may be optimal if taken at dinner time, which is associated with diabetes development (1).
Extracts of mulberry have been shown to reduce post-prandial glucose and insulin responses, but the reliability of these effects and required doses and specifications are unclear. One study aimed to assess the efficacy of various mulberry fruit extract doses, using boiled rice as the carbohydrate source. Two randomized controlled intervention studies were conducted with healthy Indian males and females aged 20-50 years (n=84 per trial), with post-prandial glucose area under the curve over 2 hours as the primary outcome (2).
Trial 1 used doses of 0, 0·37, 0·75, 1·12, and 1·5 g mulberry fruit extract mixed in boiled rice and 0 or 1·5 g mulberry fruit extract in rice porridge. Trial 2 used doses of 0, 0·04, 0·12, 0·37 g mulberry fruit extract in boiled rice. In trial 1, relative to control, all mulberry fruit extract doses significantly decreased post-prandial glucose (-27·2 to -22·9 %; all p ≤ 0·02) and post-prandial insulin (-34·6 to -14·0 %, all p < 0·01). In trial 2, only 0·37 g mulberry fruit extract significantly affected post-prandial glucose (-20·4 %, p = 0·002) and post-prandial insulin (-17·0 %, p < 0·001) (2).
Together, these trials showed that mulberry fruit extract in doses as low as 0·37 g can reliably reduce post-prandial glucose and post-prandial insulin responses to a carbohydrate-rich meal, with no apparent adverse effects. Based on a typical bioactive level in the mulberry fruits, the lowest consistently efficacious dose here of 0·37 g mulberry fruit extract would equate to about 20 g of fresh mulberry fruit (2).
One study evaluated the effect of premixed insulin, premixed insulin combined with metformin, or insulin combined with mulberry twig alkaloids on blood glucose fluctuations in patients with type 2 diabetes using continuous glucose monitors (3).
Thirty patients with type 2 diabetes and poor blood glucose control using drugs were evaluated for eligibility during the screening period. Subsequently, their original hypoglycemic drugs were discontinued during the lead-in period, and after receiving insulin intensive treatment for 2 weeks, they were randomly assigned to receive either insulin, insulin combined with metformin, or insulin combined with mulberry twig alkaloids treatment for the following 12 weeks. The main efficacy endpoint comprised changes in their continuous glucose monitor indicators changes during the screening, lead-in, and after the 12-week treatment period. Changes in glycosylated hemoglobin (HbA1c), fasting blood glucose, 1-h postprandial blood glucose, 2-h postprandial blood glucose, fasting blood lipids, and postprandial blood lipids were also measured at baseline and after 12 weeks of treatment (3).
The continuous glucose monitor indicators of the three groups during the lead-in period all showed significant improvements compared to the screening period (p<0.05). Compared with those in the lead-in period, all of the continuous glucose monitor indicators improved in the insulin combined with metformin and insulin combined with mulberry twig alkaloids groups after 12 weeks of treatment (p<0.05), except for the mean of daily difference. After 12-week treatment, compared with the insulin group, insulin combined with metformin and insulin combined with mulberry twig alkaloids groups showed improved mean blood glucose level, standard deviation of blood glucose, time in range between 3.9-10.0 mmol/L, breakfast area under the curve for each meal, lunch area under the curve for each meal, HbA1c, fasting blood glucose, 1-h postprandial blood glucose, fasting blood lipid and postprandial blood lipid indicators (p<0.05). Further, the largest amplitude of glycemic excursions, postprandial glucose excursions, mean amplitude of glycemic excursions, dinner area under the curve for each meal, and 2-h postprandial blood glucose levels of the insulin combined with mulberry twig alkaloids group were significantly lower than those of the insulin combined with metformin and insulin groups (p<0.05) (3).
These findings highlighted the efficacy of combination therapy (insulin combined with mulberry twig alkaloids or insulin combined with metformin) in improving blood glucose fluctuations, as well as blood glucose and lipid levels. Insulin combined with mulberry twig alkaloids reduced postprandial blood glucose fluctuations more than the insulin combined with metformin and Ins groups (3).
This blog outlines several studies investigating the hypoglycemic effects of mulberry and its potential benefits for blood glucose control. Here’s a summary of the key points:
1. Glucose-Lowering Effects of Mulberry Leaf Extract in Young Adults (1):
- The timing of mulberry leaf extract intake affects blood glucose levels.
- 12 young adults participated in four trials, involving morning and evening intakes of mulberry leaf extract and placebo.
- Significant reduction in blood glucose and insulin levels was observed in the evening mulberry leaf extract trial compared to the evening placebo trial.
2. Mulberry Fruit Extract Doses and Post-Prandial Glucose Response (2):
- Two randomized controlled trials assessed the efficacy of various doses of mulberry fruit extract in reducing post-prandial glucose and insulin responses.
- Significant reductions were observed with doses as low as 0.37 grams, equating to about 20 grams of fresh mulberry fruit.
3. Combination Therapy with Mulberry Twig Alkaloids in Type 2 Diabetes Patients (3):
- The study evaluated the effects of premixed insulin, insulin combined with metformin, and insulin combined with mulberry twig alkaloids on blood glucose fluctuations using continuous glucose monitors.
- Combination therapies improved blood glucose and lipid levels more effectively than insulin alone, with the mulberry twig alkaloids group showing the greatest reduction in postprandial blood glucose fluctuations.
These findings highlight the potential benefits of mulberry in managing blood glucose levels, particularly when taken in the evening or as part of a combination therapy for type 2 diabetes.
References:
1. Takahashi M, Mineshita Y, Yamagami J, Wang C, Fujihira K, Tahara Y, Kim HK, Nakaoka T, Shibata S. Effects of the timing of acute mulberry leaf extract intake on postprandial glucose metabolism in healthy adults: a randomised, placebo-controlled, double-blind study. Eur J Clin Nutr. 2023 Apr;77(4):468-473. doi: 10.1038/s41430-023-01259-x. Epub 2023 Jan 17. PMID: 36650279; PMCID: PMC10115625.
2. Mela DJ, Cao XZ, Govindaiah S, Hiemstra H, Kalathil R, Lin L, Manoj J, Mi T, Verhoeven C. Dose-response efficacy of mulberry fruit extract for reducing post-prandial blood glucose and insulin responses: randomised trial evidence in healthy adults. Br J Nutr. 2023 Mar 14;129(5):771-778. doi: 10.1017/S0007114522000824. Epub 2022 Mar 11. PMID: 35272722.
3. Meng Z, Xu C, Liu H, Gao X, Li X, Lin W, Ma X, Yang C, Hao M, Zhao K, Hu Y, Wang Y, Kuang H. Effects of mulberry twig alkaloids(Sangzhi alkaloids) and metformin on blood glucose fluctuations in combination with premixed insulin-treated patients with type 2 diabetes. Front Endocrinol (Lausanne). 2023 Nov 2;14:1272112. doi: 10.3389/fendo.2023.1272112. PMID: 38027146; PMCID: PMC10653384.
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