“A glass of wine a day keeps you alive until you are ninety-nine”, is that true?

People often say "a glass of wine a day, live to ninety-nine", and some say "too much alcohol is harmful to the body, a little alcohol is good for the mood". Are these sayings reliable? Will drinking a little alcohol every day have an impact on health in the long run?

The answer to this question is yes. Although humans have spent tens of millions of years evolving a set of abilities to deal with alcohol, it is not omnipotent after all, and it will still cause damage to the liver. So if you can't quit, you have to pay attention to protecting your liver.

Today we’re going to talk about how humans cope with alcohol.

01. How did humans evolve the ability to metabolize alcohol?

When we talk about alcohol, we often think of drinks such as liquor, beer, red wine, etc. In fact, alcohol itself is a very common substance in nature. For example, glucose, which is a basic energy substance, will produce alcohol under certain conditions. Under the action of yeast, a widely distributed microorganism, the production of alcohol is easier, and as a result, alcohol is widely distributed in nature.

A typical example is ripe fruit, which will naturally ferment into alcohol. So how to degrade and process alcohol becomes a problem that many animals must solve.

In this case, we primates may have begun to have the ability to absorb and degrade ethanol 80 million years ago. This time point is generally believed to be the era when angiosperms began to produce fleshy fruits. With fleshy fruits, there is naturally the possibility that the fruits can be fermented into alcohol after they mature.

However, our primates' ability to metabolize alcohol is not static. In 2014, the Proceedings of the National Academy of Sciences (PNAS) published a study on the evolution of primate alcohol metabolism. This study targeted an important enzyme in alcohol metabolism, alcohol dehydrogenase 4 (ADH4). By analyzing the ADH4 protein sequences of nine ancestors of primates over the past 70 million years, it was found that in history, the ADH4 of our primate ancestors was actually basically inactive towards ethanol. Instead, it had an effect on alcohols in other plants, typically the metabolic degradation of terpenoid alcohols such as geraniol, which are abundant in plant leaves [1].

But 10 million years ago, this enzyme suddenly underwent a major mutation, resulting in ADH4 becoming an enzyme that can metabolize ethanol. What happened at that time?

The answer is that the lifestyle of human ancestors changed dramatically. At that time, the climate in Africa changed significantly, causing a large number of trees to be replaced by grasslands. Under this circumstance, human ancestors were forced to walk from trees to the ground, and with it came a change in diet. The fruits picked from the trees were mainly fresh fruits, while the fruits picked from the ground at that time were mainly ripe and fallen. These ripe fruits often underwent fermentation and therefore contained some alcohol.

Faced with this situation, primates with ADH4 variants that had a better ability to break down ethanol gained an advantage, ultimately leading to our human ability to metabolize and degrade ADH4.

In fact, this evolution is not just this one huge change. Research has found that after humans entered the agricultural society, the ability to metabolize and decompose ethanol underwent another huge evolution, and this time, it is very likely related to the development of winemaking.

02. Alcohol metabolism gene alcohol dehydrogenase-1B

This time, scientists focused on another ethanol metabolism gene, alcohol dehydrogenase-1B (ADH1B), which is closely related to alcoholism. They compared the DNA of ancient humans from the Neolithic Age, the Han Dynasty, the Tang Dynasty and other periods, and found that a subtype of the ADH1B gene, H7, began to appear about 2,800 years ago. It is worth mentioning that the geographical distribution of this gene variation is very unique. In fact, H7 individuals have obvious positive selection in East Asia, which makes our ADH1B gene more powerful and has a stronger ability to metabolize alcohol [2].

Of course, seeing this, do you feel like we are chosen by God? It seems that we are a group that can decompose alcohol very well, so drinking is no problem for us?

03. Can alcohol really be completely metabolized by humans?

Can alcohol really be completely metabolized by humans? The answer is no. In fact, alcohol dehydrogenase is not the only enzyme that plays a role in the metabolism of alcohol in the human body.

When ethanol enters the human body, except for a small part that evaporates and is excreted, most of the alcohol goes to the liver. Here, the alcohol is first processed by alcohol dehydrogenase and turned into acetaldehyde, which is also an important factor in alcohol damage. Acetaldehyde must be processed by acetaldehyde dehydrogenase before it can be turned into relatively low-toxic acetic acid.

However, we are inferior in terms of acetaldehyde dehydrogenase. For example, compared with Europeans and Africans, our acetaldehyde clearance rate is lower. One important factor is that some gene mutations have occurred in acetaldehyde dehydrogenase 2. The homozygous rate of this mutation in the Chinese population is 4.5%, and the heterozygous rate is 34.27%. In other words, about 40% of the population is much slower in clearing acetaldehyde after ethanol metabolism. Therefore, many people blush after drinking, which has a lot to do with this [3].

It can be seen from this that although we have evolved a certain ability to process and metabolize alcohol, we cannot completely eliminate the risks brought by alcohol, so to a certain extent, we have to take certain measures against alcohol.

In fact, regarding the dangers of drinking, the ancients were aware of the fact that "drinking hurts the liver", and the progress of modern medicine, especially anatomy and biochemistry, has confirmed that the main site of damage caused by alcohol is the liver.

In fact, over the years, both academia and public health have been conducting popular science education on the dangers of drinking. However, the act of drinking itself has a certain degree of dependence and addiction. Coupled with the social nature of drinking itself, it is difficult for us to avoid alcohol.

In this case, choosing relatively healthy alcohol, drinking rationally and moderately, and not allowing minors to drink may be the best option.

1 Carrigan, Matthew A., Oleg Uryasev, Carole B. Frye, Blair L. Eckman, Candace R. Myers, Thomas D. Hurley, and Steven A. Benner. "Hominids adapted to metabolize ethanol long before human-directed fermentation." Proceedings of the National Academy of Sciences 112, no. 2 (2015): 458-463.

2 Li, Hui, Sheng Gu, Yi Han, Zhi Xu, Andrew J. Pakstis, Li Jin, Judith R. Kidd, and Kenneth K. Kidd. "Diversification of the ADH1B gene during expansion of modern humans." Annals of human genetics 75, no. 4 (2011): 497-507.

3 Nakano, Yukiko, Hidenori Ochi, Yuko Onohara, Akinori Sairaku, Takehito Tokuyama, Hiroya Matsumura, Shunsuke Tomomori et al. "Genetic variations of aldehyde dehydrogenase 2 and alcohol dehydrogenase 1B are associated with the etiology of atrial fibrillation in Japanese." Journal of Biomedical Science 23, no. 1 (2016): 1-9.