Newsletter #220

Hey friends! So, this week, I decided to take a look at some of the research into the surprising health effects of vinegar.

I'm a little late to the party on this topic, to be honest - for example, I remember hearing about studies showing glycemic benefits from consuming vinegar regularly a few years back, and you may have already heard about those too. But the story of how vinegar does this is pretty darn interesting. Vinegar has been shown to activate an enzyme called adenosine monophosphate activated protein kinase, or AMPK for short. AMPK is often characterized as a sort of cellular fuel gauge, because it can detect energy levels in the cell, and it intervenes in various ways when cellular energy status is compromised.

Here's how it works: in order to fuel our metabolic processes, adenosine triphosphate or ATP (our main energy source) has to be broken down into adenosine monophosphate or AMP. Consequently, when you burn a lot of energy, ATP levels go down and AMP levels will go up. When the ratio of AMP to ATP is high, this delivers a signal to the body that our energy is getting depleted. Thus, AMP-activated protein kinase comes to the rescue and scrounges up some more energy wherever it can find it. One way it does this, for instance, is by triggering autophagy, which basically means that the body gobbles up damaged cellular parts for extra energy.

As you would expect, AMPK is reliably activated in tissues throughout the body in response to states that involve energy stress, such as intense exercise and caloric restriction. This has emerged as an important target in the prevention and delay of age-related disease because one of the hallmarks of aging is dysregulation of nutrient sensing signaling pathways, including AMPK. Activation of AMPK has been shown to extend lifespan and improve health span in animal models, in part through ramping up autophagy. In fact, the anti-diabetic drug metformin is an activator of AMPK, and part of the reason why it has attracted so much interest as a potential anti-aging therapy is due to its effects on AMPK.

Right. Getting back to vinegar. Vinegar is just diluted acetic acid, and providing acetic acid itself appears to indirectly activate AMPK in some tissues, probably because the process of metabolizing acetate winds up generating some AMP, and anything that causes the accumulation of AMP can in theory activate AMPK. So does this mean that adding vinegar to your food could fight aging? One thing to keep in mind is that acetic acid doesn’t hang around for very long after you consume it, so the total impact is likely to be fairly modest. However, it’s cheap and easy, and even small effects like this add up over time, so it’s certainly worth a shot. Just make sure to practice good oral hygiene - vinegar is good for most of your body, but alas it’s pretty bad for your teeth. (This article has some good tips.)

Importantly, it looked like the subjects were losing weight from the right places too. These researchers performed abdominal CT scans on the subjects before and after the intervention, and found that most of the drop in BMI was due to reductions in visceral and subcutaneous adipose tissue. This fat loss occurred in spite of no significant differences reported in physical activity via their pedometers or in their energy intake through diet diaries (granted, the latter should probably be taken with a grain of salt). So what was going on here? Well, remember that vinegar can activate AMPK, and the role of AMPK is to generate more energy in response to apparent privation. One way it does this is by increasing expression of enzymes that promote fatty acid oxidation - basically telling the body to start burning more fat - and this has been shown in animal models where acetic acid was administered. Further support for this mechanism comes from a more recent RCT, in which Korean researchers found that women who drank vinegar daily for eight weeks experienced reductions in visceral adipose tissue, and biopsies of their fat tissue revealed significant activation of AMPK.

Researchers recruited 45 healthy adults deemed to be at elevated risk of metabolic syndrome. Subjects were randomly assigned to either consume red wine vinegar daily or a control treatment for eight weeks. Analysis revealed significant reductions in both blood sugar and insulin in the intervention group at the end of the study period. Now, this may be in part because of how vinegar interferes with enzymes that break down starch, thus slowing down the digestion of complex carbohydrates. However, these researchers also observed a significant decrease in insulin resistance (-8.3%) in the vinegar group, while the control group experienced an increase in insulin resistance (+9.7%), and this happened despite any significant changes in body weight in these subjects. Here, again, is where AMPK could be playing a role. To make sure that muscle cells refuel (for example during exercise), AMPK increases the activity of glucose transporters to help skeletal muscle take up sugar, which in turn lowers blood glucose. This is a major reason why regular exercise increases insulin sensitivity, and vinegar appears to be mimicking this to a degree.

Researchers in Japan analyzed nutritional data from 746 participants over the age of 40, who had also had their blood pressure measured and categorized. These researchers paid particular attention to consumption of sunomono, a traditional side dish made with sliced cucumber or seaweed in rice vinegar. The reason why they zeroed in on this is because it is a substantial and reliable source of vinegar in the diet - people usually consume all of the vinegar included in the bowl - and other uses of vinegar are sort of hard to quantify in dietary surveys. Indeed, they found that men who ate sunomono tended to have lower blood pressure. This by itself might not be super compelling but it’s notable in light of the fact that the participants in the weight loss study described above also experienced a significant reduction in systolic blood pressure, from 127mmHg to 121 mmHg. Plus animal research has shown this effect as well. In rats that are bred to be predisposed to hypertension, administration of acetic acid boosted the AMP/ATP ratio and in turn activated AMPK in the arterial walls of these rodents. This dropped their blood pressure because AMPK increases production of nitric oxide in the walls of blood vessels, which helps them dilate.

Thanks for reading, enjoy the weekend, and we'll see y'all next week!

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