Every day for years I have made my best effort to consume vinegar with every meal. Whether this is apple cider vinegar mixed in carbonated water or a touch of white vinegar on steamed greens or rice, I always try and find a way to have my vinegar. If you asked me why, I would say that it helps reduce post-prandial glycemia (the blood glucose response following a meal). In fact, it was the first guest-post article I had written for Adel Moussa over at SuppVersity. Since then I have never really given vinegar a second thought, until a newly published study popped into my inbox that once again brought vinegar to my attention. Only this time, I want to do it more justice than I had in the short article I wrote for Adel.

So, what is vinegar?

Vinegar is a liquid consisting mainly of water and acetic acid, which is responsible for the tart flavor and sour taste. However, although acetic acid identifies the product as vinegar, they are not one and the same. Acetic acid is produced and excreted by acetic acid bacteria found universally in foodstuffs, water, and soil, and is produced naturally as fruits and other fermentable carbohydrate sources spoil. Vinegar is typically four to eight percent acetic acid by mass, and contains various other compounds including organic acids (formic, lactic, malic, citric, succinic, and tartaric), vitamins, minerals, amino acids, and bioactive compounds. Vinegar is thus not equivalent to diluted acetic acid.

What can vinegar do for you?

There is no shortage of research investigating the effects of vinegar on blood glucose management. As of October 2014, 20 human intervention trials in both healthy and diabetic populations have evaluated the glycemic effects of vinegar consumption and only three have failed to find a beneficial effect.

The first failed experiment involved seven healthy adults who consumed 50 g of sucrose with or without 60 mL (4 tbsp) of strawberry vinegar. Although postprandial glycemia (PPG) was similar between the conditions, vinegar resulted in a 20% reduction in the overall insulin response. The second failed experiment involved 16 adults with type-2 diabetes (T2D) who consumed baked beans, rice, and a salad with or without 50 g of grape vinegar. Vinegar consumption actually increased PPG without affecting insulin. The final failed experiment involved 12 elderly adults with T2D who consumed a 75 g glucose beverage with or without 25 g white vinegar. There was no difference in PPG or insulin between the conditions.

The reason for why these failures is best  explained by the work of Johnston et al, who conducted four separate double-blind, randomized, crossover trials to investigate the dosage, timing, and application of vinegar for blood glucose management. These trials are outlined in the table below.

Collectively, these four trials revealed that consuming vinegar with meals reduced the glycemic response by 20-25% compared to a placebo, but that there was no effect when the vinegar was consumed alongside dextrose, five hours prior to the test meal, or when acetate was consumed.

The dose of vinegar may be an important consideration. In trial 1, PPG was unaffected with 2 g of vinegar and marginally reduced (6-12%) with 20 g of vinegar but significantly reduced by 23-28% with 10 g of vinegar. These results are in-line with the second failed experiment using a 50 g vinegar dose and suggest that more may not be better. However, the vast majority of trials documenting benefits equivalent to the 10 g dose used 20-30 g, and Ostman et al. demonstrated a dose-dependent effect of vinegar’s benefits with 18, 23, and 28 g doses. The reason for these discrepancies is not clear, and it appears that 1-2 tablespoons (15-30 g) is a prudent amount of vinegar to consume with a starchy meal.

The timing of the vinegar is another important consideration. In trial 2, there was no effect of vinegar when consumed five hours prior to the test meal, suggesting its mode of action for reducing PPG is acute. It has been suggested that vinegar acts to slow gastric emptying and inhibit carbohydrate digestion. The former has been supported by studies using an indirect tracer in healthy participants and ultrasonography in type-1 diabetics with gastroparesis, with reasons being related to vinegar’s acidity (acetic acid). This hypothesis is further supported by trial 4 that showed no effect of acetate on PPG, but other research has compared vinegar and vinegar neutralized with baking soda and shown no differences between the two with regard to gastric emptying rate despite only vinegar resulting in a 31% reduction in PPG.

Regarding inhibition of carbohydrate digestion, acetic acid has been shown to significantly inhibit disaccharidase (sucrase, maltase, trehalase, and lactase) activity by 40-50% in vitro. This would explain why acetate shows no benefits independent of effects on gastric emptying, and also why trial 3 and the first and third failed experiments found no benefit of vinegar consumption. However, the only human trial to investigate starch absorption found no inhibition by vinegar; although, these results must be viewed cautiously because there were only five subjects and the researchers admit that their method of evaluating carbohydrate absorption was novel and unproven.

Clearly vinegar’s acetic acid component and acidity play a role in mediating its beneficial effects, but whether it does so through slowing the digestion and absorption of carbohydrates is contested. A more remarkable explanation is that acetic acid is an insulin sensitizer. This novel concept has been supported in animal studies but only recently has it been confirmed in humans thanks to the work of Mitrou et al from Greece, who measured PPG and insulin and forearm muscle blood flow and glucose uptake in T2D subjects after consuming a mixed meal with or without 30 mL (2 tbsp) of vinegar. Over the following 300 minutes, blood glucose uptake into the skeletal muscle of the forearm was 32% greater in the vinegar than the placebo condition despite no differences in blood flow and a 21% reduction in insulin.

Glucose uptake and utilization by muscle cells is entirely dependent on the action of insulin with several exceptions. Therefore, the reduction in insulin concentrations that occurred alongside enhanced glucose uptake suggests that the hypoglycemic effect of vinegar may be mediated through a direct effect on muscle tissue. There is certainly an abundance of animal trials to support this idea.

In diabetic mice fed a diet containing 0.3% acetic acid by weight (~2 tbsp of vinegar per pound of food) for eight weeks, fasting glucose, HbA1c, and liver fat were significantly reduced, and liver and skeletal muscle glycogen significantly increased compared to the control group. These effects were attributed to reductions in the expression of G6Pase, PEPCK, and SREBP-1 via an increase in the expression of AMPK, which would collectively reduce gluconeogenesis (creation of glucose from other compounds) and lipogenesis (creation of fat) within the liver.

These effects have been corroborated under a more acute timeframe in healthy normal rats as well. For ten days, Fushimi and Sato fed rats a commercial non-purified chow with or without 0.07% acetic acid, which is far less than the previous study and amounts to about ½ tbsp of vinegar per pound of food. Importantly, the rats were starved on the last day to deplete glycogen stores and were then fed a final meal before being monitored for eight hours and then sacrificed. The acetic acid group had significantly greater glycogen concentrations in the liver and skeletal muscle than the control group four hours after the final meal, but there were no differences in the maximum amount of glycogen content in any tissue, suggesting that acetic acid enhances glycogen repletion but does not lead to super-compensation. Gene expression analyses suggested that these effects were owed to a transient reduction in skeletal muscle and liver glycolysis (the breakdown of glucose for use as energy) coupled with an enhancement of fatty acid oxidation.

Another study revealed that acetic acid directly stimulates the expression of muscular GLUT4 and genes involved in fatty acid oxidation within fat tissue, again mediated through increases in AMPK.

Although no healthy human trials have evaluated glucose uptake with vinegar consumption, there is reason to believe that the effects may be even more pronounced because vinegar consumption has been shown to stimulate vasodilation in otherwise healthy postmenopausal women through an increase in the expression of nitric oxide synthase. It is well known that vasodilation is considered an important component of insulin-mediated glucose uptake. It may be that in T2D the defect in vasodilatation cannot be reversed by vinegar ingestion, since vinegar-stimulated increases in blood flow have also been observed in individuals with impaired glucose tolerance but not T2D.

Now, although I dislike ending on a less than ideal note, the majority of explanatory data is derived from animal models and the scant human evidence that does exist suffers from incredibly small sample sizes (usually around 10-20 people) and the risk of publication bias, since positive results have a better chance of being published than negative results. There is also a paucity of evidence evaluating the long-term impact of vinegar ingestion. Finally, more research to evaluate the potential mechanisms of vinegar is needed as some data appears contradictory. For instance, acetic acid would be neutralized by pancreatic bicarbonate as soon as it leaves the stomach, meaning that acetate would be absorbed into the blood stream. If that were the case, then why did consuming acetate directly not benefit post-prandial glycemia through its effects on muscle tissue? Similarly, if acetic acid is an insulin sensitizer, then why were no effects observed when consumed alongside pure glucose?

Despite these short-comings, all studies reported that vinegar was well-tolerated and without adverse effects. Vinegar appears to benefit blood glucose management through increasing insulin sensitivity and reducing the digestion and absorption of starchy carbohydrates. For both healthy and diabetic people, consuming 2 tbsp (30 mL) of vinegar with every meal, as a dressing or mixed into carbonated water (my preference, with a small amount of stevia to remove the acid-sting), appears to be a safe and affordable method to improve one’s health.