Protein source affects plasma AGE markers

Group of non dairy lactose free vegan milks and ingredients shot from above on kitchen table. Soy, coconut, almond, oat and rice milks. Source of healthy plant based proteins
Soy protein supplementation can significantly increase the plasma levels of the AGE N(6)-(1-carboxymethyl)-L-lysine (CML) – an AGE found to be elevated in patients with type 2 diabetes and coronary heart disease, says a new study from Singapore. (Image: Getty/Fcafotodigital)

Protein supplementation, depending on the types of protein taken, can affect the plasma levels of different advanced glycation end products (AGEs), according to a new RCT from Singapore.

For instance, soy protein supplementation can significantly increase the plasma levels of the AGE N(6)-(1-carboxymethyl)-L-lysine (CML) – an AGE found to be elevated in patients with type 2 diabetes and coronary heart disease.

Casein protein supplementation, on the other hand, showed a significant increase in plasma levels of the AGE pentosidine, where high levels are identified as a risk factor for fractures in older adults with diabetes.

AGEs are a large group of complex and heterogeneous compounds and are obtained from diets or produced in the body via the Maillard reaction between reducing sugars and free amino groups, such as on proteins.

Existing studies showed that higher blood levels of AGEs were associated with a higher risk of cardiovascular diseases, neurodegenerative diseases and type 2 diabetes.

Explore related questions

One way that AGEs increase the risk of chronic disease is by altering the structures of essential biological macromolecules via chemical modification of proteins, lipids and nucleic acids. This may cause a loss of their respective functions and collectively contribute to cellular dysfunction and tissue damage.

In the present study, although plasma CML and pentosidine increased significantly, no alterations were seen in dietary, skin and total circulating AGE levels, the researchers wrote in Nutrients.

“In this study, we found that protein supplementation does not alter levels of circulating total AGEs in blood and accumulated AGEs under the skin...” they wrote. “However, different protein sources resulted in differential responses in specific AGEs.”

Study method

Sixty-five older adults aged 60 to 80 took part in this 16-week single-blinded, three-arm parallel RCT.

They were randomized to either the control, 20 grams of casein protein isolate or 20 grams of soy protein isolate powder per day.

The protein powders were from the UK brand Myprotein and were consumed together with 250 mL of UHT low-fat milk. The protein content of the casein and soy protein isolate powders was 16.4 and 18.0 g protein/20 g of powder, respectively.

All participants were also assigned to follow the My Healthy Plate diet created by Singapore’s Health Promotion Board, comprising three main food groups, namely, wholegrains, meat and others, and fruits and vegetables daily.

To assess the effects of different protein supplementation, blood pressure, dietary intake, skin and blood AGE levels were measured before and after the intervention.

The study was funded by the National University of Singapore Mind Science Centre and the National University of Singapore, Bezos Centre for Sustainable Protein–Bezos Earth Fund.

The study is also said to be the first RCT to investigate the effects of protein supplementation with different protein sources on different AGE levels while adhering to an HDP among older adults.

Why the increase?

The increase in plasma CML levels in the soy protein group could be due to its amino acid composition, such as the presence of high lysine residues in soy protein as compared to milk proteins.

On the other hand, the increase in pentosidine in the casein protein group should be interpreted with caution, as the time-by-group interaction was not statistically significant, said the researchers.

They pointed out how the increase in pentosidine could be related to the digestion characteristics of casein, which has a long gastrointestinal digestion time.

“Casein is generally considered a slowly digested protein and has a relatively long gastrointestinal residence time, resulting in a more sustained release of amino acids,” the researchers wrote. “This prolonged availability of amino acids may potentially influence endogenous AGE formation via crosslinking between lysine and arginine from casein proteins with reactive carbonyl species, like 3-deoxyglucosone, and fructose present in the diet, which increases the formation of Pen in the gastrointestinal tract.”

However, they also said that since postprandial amino acid concentrations and AGE formation pathways were not directly measured in the study, the explanations remained speculative.

Still, the researchers highlighted that plant protein may have beneficial effects on AGE levels, as compared to animal protein.

Citing a study published in Food Function last year, researchers highlighted that obese prediabetic individuals consuming black soymilk had significantly lower circulating fluorescent AGE levels compared to those consuming pork protein.


Source: Nutrients. doi: 10.3390/nu18172925 “Investigating the Impact of Protein Supplementation from Different Sources on Advanced Glycation End Products in Older Adults in Singapore Following a Healthy Dietary Pattern.” Authors: Ting, M. et al.