Could Having ALDH2 Deficiency Offer Unexpected Heart Protection?

If you get a red face after drinking alcohol, you might have a deficiency in an enzyme called aldehyde dehydrogenase 2 (ALDH2). This enzyme plays an important role in breaking down acetaldehyde, a toxic byproduct of alcohol metabolism that is bad for us in many ways. Interestingly, recent research has suggested that ALDH2 deficiency might also offer unexpected heart protection by influencing the risk of obesity and atrial fibrillation.

Understanding ALDH2 Deficiency

ALDH2 deficiency, sometimes referred to as Asian flush, is most common among East Asian populations and has been linked to various cardiovascular conditions. This deficiency makes it harder for the body to detoxify aldehydes, leading to increased oxidative stress and tissue damage.

Given its link with various cardiovascular conditions, it is surprising that ALDH2 deficiency is being shown to offer some degree of heart protection (at least in mice).

Does ALDH2 Deficiency Actually Protect Our Hearts?

A recent study published in the International Journal of Molecular Sciences explored the connection between ALDH2 deficiency, obesity, and atrial fibrillation (a condition involving the chaotic and irregular beating of the heart). Researchers from the Cardiovascular Division at Chang Gung Memorial Hospital and Chang Gung University College of Medicine in Taiwan, used mice to mimic human ALDH2 deficiency and fed them a high-fat diet to induce obesity. These mice were then compared to wild-type mice under the same conditions.

The study made some interesting findings in the following areas:

Oxidative Stress and ALDH2 Deficiency

Both ALDH2 deficient and wild mice showed higher levels of harmful molecules called reactive oxygen species when fed a high fat diet. However, what the researches noticed next was very interesting:

"The ALDH2*2 KI mice did not exhibit a greater propensity for AF compared to the WT controls"​​

They found that the ALDH2 deficient mice (referred to above as ALDH2*2 KI mice) didn't have a higher risk of developing atrial fibrillation compared to the normal wild mice. This suggests that there might be some degree of protection that helps reduce the risk of atrial fibrillation in ALDH2 deficient mice.

According to the researchers, this might be because their bodies activated protective pathways, specifically the Nrf2 and HO-1 pathways that have been found to reduce oxidative stress and inflammation.

Inflammation and Fibrosis

Obesity can cause the heart's tissue to scar, a process known as fibrosis. Interestingly, the study found that ALDH2 deficient mice had less scarring than normal mice, despite having higher levels of a protein that promotes fibrosis, called TGF-β1. The researchers noted that:

"Atrial fibrosis did not proportionally increase with TGF-β1 expression in ALDH2*2 KI mice, suggesting compensatory upregulation of the Nrf2 and HO-1 pathway, attenuating fibrosis"​

The researchers were expecting to see more scarring in the heart (fiborosis), but didn’t. This suggests that the Nrf2 and HO-1 pathways were activated in the ALDH2 deficient group, which helped reduce the scarring and protected the heart tissue.

Body Weight and Metabolic Parameters

ALDH2-deficient mice did not gain significantly more weight than normal mice on a high-fat diet. This finding contrasts with some human studies where ALDH2 deficiency is linked to a higher risk of obesity and related health problems.

In humans, ALDH2 deficiency has indeed been linked to a higher risk of obesity and related health problems. This deficiency makes it harder for the body to break down certain toxic substances, leading to more oxidative stress and metabolic issues.

Studies have found that people with ALDH2 deficiency often have problems like glucose intolerance, insulin resistance, and fatty liver disease, all of which are common in obesity.

However, in the study with ALDH2-deficient mice, the results were different. These mice did not gain significantly more weight compared to normal mice when both groups were fed a high-fat diet. This suggests that the way ALDH2 deficiency affects metabolism might be different in mice than in humans, or that other protective mechanisms are at work in the mice.

Implications for People with ALDH2 Deficiency

The study found that having ALDH2 deficiency, which causes "Asian flush," affects heart health in complex ways, especially in obesity. One important discovery is that the Nrf2 and HO-1 pathways help protect the heart, suggesting they could be targets for treatments to reduce atrial fibrillation risk in people with ALDH2 deficiency.

This opens up new research opportunities to understand how lifestyle choices like diet and drinking alcohol interact with genetic factors to impact heart health.

Conclusion

While ALDH2 deficiency is known for causing "Asian flush" (a red face after drinking alcohol), it also impacts other health issues like obesity and irregular heartbeats (atrial fibrillation). In the above-mentioned mouse study, ALDH2-deficient mice didn't gain more weight on a high-fat diet, which is different from what some human studies have found. In humans, ALDH2 deficiency is usually linked to higher risks of obesity and related problems like insulin resistance and fatty liver disease.

Interestingly, the study found that ALDH2-deficient mice had a lower risk of developing a heart condition called atrial fibrillation compared to normal mice, even though they had more oxidative stress. This was surprising because human studies usually show a higher risk of heart problems in people with ALDH2 deficiency.

The differences between the mouse and human studies show that results in animals don't always match up with humans. But by understanding these differences, scientists can develop better treatments for ALDH2 deficiency. The protective pathways found in mice, Nrf2 and HO-1, could be new new areas of focus for research around reducing heart risks in people with ALDH2 deficiency.