According to researchers in Thailand and the US, while omega-3 could reduce the amount of proteinuria in both type 1 and type 2 diabetes, the association was only significant among people with T2D (p=0.03).
Proteinuria is commonly used as a predictor of cardiovascular and stroke events among diabetic patients, and between 30 to 40% of patients with diabetes will develop diabetic kidney disease which is characterised by proteinuria.
Researchers say of their current findings that omega-3 fatty acids could possibly help diminish proteinuria and subsequently reduce cardiovascular complications and stroke incidence among people with T2D.
Even though several meta-analyses have previously investigated the effects of omega-3 fatty acids on proteinuria, the possible benefits of omega-3 fatty acids remain unclear, especially among diabetic patients.
They added: “This is the largest meta-analysis to assess the treatment effect of omega-3 fatty acids on proteinuria and other outcomes among different types of diabetic patients.”
The study was published in the journal, PLOS ONE.
Selection of trials
The researchers conducted electronic searches in PubMed, Embase and Cochrane Central Register of Controlled Trials from 1960 to 2019 and selected 10 RCTs with a total of 344 participants.
The criteria for RCTs were those examining the effect of omega-3 fatty acid supplementation compared to control on proteinuria or albuminuria, and included both T1D and T2D patients. There were no restrictions on sample size or study duration.
There were three trials conducted in North America (USA), three in Europe (UK, Denmark, Czech), three trials conducted in Asia (two in Japan, South Korea) and one trial conducted in Australia.
There were five trials that included only T2D, three trials that included only T1D and two trials that included both T1D and T2D.
In these RCTs, sample size varied from nine to 79 patients. Study follow-up durations ranged between 6 to 52 weeks.
Omega-3 supplementation was taken in the form of fish oil containing either EPA or DHA or a combination of both.
Effect on type 2 diabetes
Results from the meta-analysis revealed among T2D group with 213 participants, omega-3 fatty acids could significantly reduce proteinuria (p=0.03) when compared to control group. However, among T1D group with 97 participants, there was no significant difference in proteinuria (p=0.95) between omega-3 fatty acids group and control group.
Researchers explained their findings: “The pathophysiology of diabetic nephropathy in T2D and T1D patients is somewhat different. For T2D, proteinuria could be caused by various etiologies including but not limited to insulin resistance, concomitant hypertension and obesity,
“One of the possible explanations would be that among T2D there are pro-inflammatory cytokines generated from abundant adipose tissue as a part of obesity in T2D. This inflammatory response leads to proteinuria among diabetic nephropathy. Omega-3 fatty acids help reduce insulin resistance as well as pro-inflammatory responses from adipose tissue.
“This effect might result in lower proteinuria compared to patients with T1D which proteinuria is mainly through polyol, hexosamine, advanced glycation end product and protein kinase C (PKC) pathways.”
Half a year supplementation
In addition, only T2D patients who received omega-3 fatty acids for at least 24 weeks (165 participants) had a significant decrease in proteinuria compared to control group (p=0.04).
Researchers chose 24 weeks as the cut off point since this value was the median.
Studies with follow-up period less than 24 weeks failed to show significant difference in proteinuria (p=0.68).
On the other hand in T1D patients, there was no significant difference in decreasing proteinuria even supplementing with omega-3 fatty acids for more than 24 weeks (38 participants) (p=0.93).
Limitations and recommendations
While the strength in this meta-analysis was its use of RCTs, there were some limitations.
“Different doses and components of omega-3 fatty acids in each trial as well as different control group could lead to heterogeneity and we did not have enough data to perform a dose response meta-analysis,
Moreover, it was also difficult to conclude whether the effects on proteinuria or other outcomes were caused by EPA or DHA,” researchers acknowledged.
Diabetes affects an estimated 350 million people worldwide, which is predicted to grow to over 550 million people by the year 2035, hence studies on potential preventive treatment will be impactful.
Researchers suggested clinical trials with more participants, longer duration of follow-up, analysing markers of oxidative stress, inflammation and urine protein fingerprinting should be extensively studied to address the potential mechanism of omega-3 fatty acids on delaying proteinuria, cardiovascular complications and incidence of stroke among diabetic patients.
Source: PLOS ONE
https://doi.org/10.1371/journal.pone.0228315
“The effects of omega-3 fatty acids on diabetic nephropathy: A meta-analysis of randomized controlled trials”
Authors: Api Chewcharat, et al.
