Published: February 7, 2024
Revised: February 13, 2024
Over the last few blog posts, I covered the key roles of visceral and ectopic fat as well as insulin resistance in the development of many chronic diseases, including type 2 diabetes, cardiovascular disease, kidney disease, liver disease, and many types of cancer.
With this blog post here, I am starting a new series to discuss dietary factors to prevent or reverse insulin resistance. A central part of this is how to prevent or reverse excess weight gain, and specifically the accumulation of visceral and ectopic fat.
And we are starting with what I consider to be among the lowest-hanging pieces of fruit, and that has to do with alcoholic and sugar-sweetened beverages.
In most societies around the globe, drinking beverages that contain alcohol or sugar is an important part of the culture. It can undoubtedly be wonderful to celebrate a special event with a glass of champagne, enjoy a nice wine while dining out, or have an ice-cold lemonade or beer on a hot summer day. And, of course, I am not opposed to this type of drinking to help make a special occasion even more special. However, the dose makes the poison. If it’s not an occasional treat but a regular habit, it’s a health risk. And I think most people are not clear on how damaging these beverages are for their health if consumed regularly.
So, with this blog post, I will explain how alcoholic and sugar-sweetened beverages are a real metabolic double whammy, with major effects on calorie intake, body weight and fat mass on the one hand, and liver fat content on the other.
The Impact of Alcoholic and Sugar-Sweetened Beverages on Calorie Intake
Quite a few studies have looked into the effect of drinking alcoholic or sugar-sweetened beverages on overall calorie intake in a meal. In most studies, participants were given the same standardized meal, on different days. They were usually given more than they could eat, and asked to eat only as much as they needed to feel comfortably full. On some days, the investigators served a glass of water with the meal, and while the participants could still decide how much of the food to eat, they had to drink all of the water. By doing this a few times, investigators could measure how much of this specific meal participants would choose to eat. Let’s say, on average, they ate 600 kcal worth of food in one sitting.
Now, the research question was: what if we don’t serve water, but instead serve a beverage that contains calories, such as soda or beer? For example, if we serve a glass of regular sugar-sweetened soda containing about 150 kcal, and participants have to drink this, do they end up eating less of the solid food? And will it be exactly 150 kcal less? One way to think about this is: do people compensate for the energy in soda by eating less of the solid food?
As the figure above shows, the answer is quite clearly no. In most of these types of studies, adding soda, juice, wine, or beer to a meal does not change the consumption of solid foods, or at least not meaningfully. There are some exceptions, however, which suggest that the relative timing of beverage and solid food intake, as well as the composition of the solid food meal, matter. In most studies, however, beverage calories are simply consumed on top of the calories from the solid food participants chose to eat, and there is usually no or very little compensation. In fact, one study suggests that people even eat more solid food when they are served beer with that food.
The take-home message is that if you sit down to eat a meal, you are likely to consume significantly more calories if the meal contains a beverage such as soda, fruit juice, an energy drink, lemonade, beer, or wine.
Now, that’s just the impact of an alcoholic or sugar-sweetened beverage on calorie intake within a single meal, and you may wonder whether this effect would persist if we constantly consumed such drinks with our meals.
My lab conducted a clinical study in which we investigated this. As in the single meal studies, we also provided participants with all of their solid food, but not just for one meal, but for eight continuous days. Participants were also given four servings per day of a sweetened beverage, the consumption of which was mandatory, while the consumption of the solid food was ad libitum, which means that they could eat as much or as little of the solid food as they wanted. We conducted this study in two randomized cross-over design experiments. In the first experiment, participants received, in random order, four servings per day of beverages sweetened with aspartame, 100% fructose, or 100% glucose, each for eight consecutive days, with identical solid food provided. The second experiment had the exact same design, except that now we provided beverages sweetened with high-fructose corn syrup, 100% fructose, or 100% glucose. In all studies, solid food was provided well in excess of what participants were expected to require. All food was weighed during preparation and packaging, and all leftovers were weighed upon return, in order to assess the total calorie intake over the course of each eight-day period.
We found that people consistently consumed more calories, even over eight days, when they were drinking sugar-sweetened beverages than when they were drinking diet soda sweetened with aspartame. Total calorie intake was, on average, 14% higher during the diet phases when participants were drinking sugar-sweetened beverages, which is a huge difference.
The type of sugar used did not matter, by the way, as calorie intake was almost exactly the same independent of whether the beverages were sweetened with fructose, glucose, or high-fructose corn syrup, which is a mixture of fructose and glucose.
We also have evidence that replacing sugar-sweetened beverages with water is associated with substantially lower overall calorie intake, i.e., people do not spontaneously consume more solid food calories to compensate for sugar-sweetened beverage calories that have been replaced by water.
As far as I know, we do not have similar data for how alcoholic beverages affect ad libitum calorie intake over a few days, at least not from a similarly well-controlled study where all of the food and beverages were provided. My best guess would be that regularly drinking beer or wine or hard liquor would have a similar impact on overall calorie intake.
We can conclude that in the course of a meal, calorie consumption increases significantly if we have a sugar-sweetened or alcoholic beverage with that meal. That is because liquid calories from such drinks do not seem to be as satiating as calories from solid food, and as a result, we do not spontaneously reduce our intake from solid food to compensate for the calories in the drinks. You can think of liquid calories basically as just being added on top of the solid food calories. It’s almost as if liquid calories are a burglar that sneaks by our satiety-regulating alarm system largely undetected. For sugar-sweetened beverages, we also have solid evidence that this effect extends over several days, and that replacing sugar-sweetened beverage calories with water sustainably lowers total calorie intake.
One question I often get asked is whether this effect extends to milk. The short answer is almost certainly not. The data on milk is a bit varied, and effects on calorie intake differ a bit for low-fat vs. whole milk, but overall calorie intake does not seem to go up nearly as much, or at all, when we drink milk with a meal. Some studies actually show that a meal containing milk is more satiating, and reduces calorie intake at that meal or at a later meal.
If calorie intake is increased in people who consume alcoholic or sugar-sweetened beverages, does this mean that regularly consuming such beverages leads to weight gain?
The Impact of Alcoholic and Sugar-Sweetened Beverages on Body Weight
For sugar-sweetened beverages, the answer is clearly yes, regularly consuming these beverages leads to weight gain. In observational studies and randomized controlled trials, adults and children who drink the most sugar-sweetened beverages gain more weight and have a higher risk of developing obesity than those who don’t drink sugar-sweetened beverages. And people who are asked to reduce their consumption of sugar-sweetened beverages tend to lose weight compared to those who continue drinking sugar-sweetened beverages.
For alcoholic beverages, the evidence is not as clear.
What we can say with some confidence is that regular and heavy drinking likely does promote weight gain. I am saying “likely” here because this is largely based on observational studies. Heavy drinking is usually defined as two drinks per day, or more.
The biggest problem in this field is that we barely have any solid experimental evidence. All of the randomized controlled trials that have been conducted on the impact of alcoholic beverages on body weight tended to have very small sample sizes of often just 12 or 14 participants; they usually included only beer or wine, not other alcoholic beverages; they tended to be short in duration; and they tended to study low to moderate amounts of alcoholic beverages. This is particularly problematic in studies looking at weight change, an endpoint that is notoriously variable in the short term, with large differences in response between people even to very standardized interventions. We simply don’t have data from a large, long-term study in which people were randomized to different groups drinking various amounts of alcohol daily, or to be totally abstinent. It would be hard to find enough people willing to be randomized to such very different interventions, and it would be ethically questionable to have participants regularly consume large or even moderate amounts of alcohol for a long period of time.
The existing data from randomized trials is, therefore, very limited, and mostly shows that moderate alcohol intake in the short term doesn’t seem to affect body weight. That could mean that modest drinking doesn’t have any effect on body weight, or – my best estimate – that modest drinking only has a small effect on body weight that is too small to be detectable by these small, short-term studies. This idea is supported by a very comprehensive analysis of the relationship between changes in the consumption of alcoholic beverages and weight changes, which suggests that any increase in daily alcohol consumption is associated with a small, but significant weight gain. There is also evidence suggesting that the impact of alcoholic beverages on body weight is dependent on which specific type of alcoholic beverage we are drinking. Specifically, weight gain seems to be more pronounced in people regularly drinking beer than wine.
So what the available data cumulatively suggest is that regularly consuming alcoholic and particularly sugar-sweetened beverages increases calorie intake and body weight. But that’s not the only negative health consequence of regularly drinking sugar-sweetened or alcoholic beverages. Let’s move on to the second part of this double whammy, and that is …
The Impact of Alcoholic and Sugar-Sweetened Beverages on Liver Fat Content
As I have mentioned in previous blog posts, the liver is not a fat-storage organ, and fat in the form of triglycerides should normally make up close to zero percent of liver tissue. However, through a number of different factors, fat can accumulate in the liver, and whenever the fat content increases to more than 5% of the liver tissue, we call it fatty liver disease.
Fatty liver disease is a major health concern, and not to be taken lightly. It is a major contributor to insulin resistance, and also a risk factor for advanced liver diseases, including liver fibrosis, cirrhosis, and liver cancer. To say this plainly: you do not want to store fat in your liver.
Unfortunately, fatty liver disease is extremely common, and about a third of all adults worldwide are now thought to have fatty liver disease. Actually, just the global prevalence of non-alcoholic fatty liver disease (NAFLD) has recently been estimated at 32%, and this does not include alcoholic fatty liver disease.
There are several factors that contribute to the accumulation of fat in the liver. One is a gain in body weight and fat mass, specifically when the extra fat can no longer be safely stored in the subcutaneous fat tissue. I talk about this in detail in a separate blog post about the so-called Personal Fat Threshold hypothesis by Dr. Roy Taylor.
Now, you can probably guess why I am mentioning fatty liver here in this blog post. We have seen that the regular consumption of sugar-sweetened and alcoholic beverages causes excess calorie intake. These extra calories are converted to fat and need to be stored. Initially, the extra calories may be stored in subcutaneous fat tissue. However, over the course of many years, depending on how much fat we personally are able to store in our subcutaneous fat tissue, this primary storage location for fat will eventually be filled to capacity. And when it’s full, it will no longer be able to take up additional fat. That leads to an increased flow of fat in the form of free fatty acids from the subcutaneous fat tissues to visceral fat depots as well as ectopic fat depots, including the liver (see figure below). This flow of free fatty acids from the subcutaneous fat tissue to the liver occurs to some degree all the time, in everyone, mostly in the fasting state to fuel the body while we are not eating. However, if our subcutaneous fat tissues are filled to capacity, and have become insulin resistant as a result, more and more free fatty acids will flow to the liver. The liver may usually temporarily store a little bit of fat, and then try to burn it to generate fuel. We call this fat oxidation. Or it may package the fat up with other fats and cholesterol as well as some proteins in very-low-density lipoprotein or VLDL particles and transport the fat back to the fat tissue. Now, you can maybe already see a problem here: the liver doesn’t want the fat, and doesn’t want to store too much of it. So it wants to transport the fat back to the fat tissues, but these also don’t want it because they are already overly full.
The liver wants to get rid of the accumulating fat by burning it or by transporting it out of the liver cells using VLDL lipoprotein particles. However, if now the amount of fat that arrives in the liver cells from the subcutaneous fat tissue exceeds the organ’s ability to handle fat, then more and more fat will accumulate in the liver cells. So yes, because sugar-sweetened and alcoholic beverages lead to weight gain, that’s one way through which these drinks can contribute to the accumulation of fat in the liver.
But there is another mechanism that is more specific through which alcoholic and sugar-sweetened beverages contribute to fat accumulation in the liver above and beyond this effect mediated by weight gain.
To understand this, let me show you what happens to alcohol. Let’s assume an adult man drinks 3 cans of beer. That’s equivalent to about 40 g of alcohol. If we measured the concentration of alcohol in his blood for a few hours afterwards, it would look roughly as illustrated in the figure below. From a baseline concentration of 0 mg/dL, we would reach a peak of maybe 60 to 70 mg/dL. From there, the concentration would slowly decline back to baseline, which usually takes about 4-6 hours. Considering that this man may have about 6 liters of blood in total, this means that the total amount of alcohol in all of his blood at the peak is about 4 g. So how can that be? He drinks 40 g of alcohol, but at no time is there more than 4 g of alcohol in his entire blood? Where does all of the alcohol go?
Well, alcohol that we absorb into our blood enters the portal vein, which leads right to the liver. And the liver is by far the primary organ that takes up and degrades alcohol in the human body. So immediately after absorption, much of the alcohol that we just consumed ends up inside of liver cells. That’s why the alcohol concentration in peripheral blood doesn’t increase all that much.
So what happens with the alcohol in the liver? Alcohol is not a healthy substance for any cell, and so the liver cells degrade it, mostly by burning it for energy. Now, the liver cells only need a pretty small amount of energy, so while they are burning alcohol, they stop burning other stuff, specifically fat. So, an additional mechanism through which alcohol affects the amount of fat in the liver is that alcohol acutely inhibits or even stops fat oxidation in the liver. And remember, fat oxidation is one of only two ways through which the liver cells can get rid of fat.
If too much alcohol is coming in too fast, some of it can even be directly converted to fat. So alcohol does not just inhibit fat oxidation, but also can directly increase the amount of fat made by the liver.
And this is very consistent with a large body of evidence directly linking excessive alcohol consumption to fatty liver disease. In animal models of alcoholic liver disease, excessive alcohol feeding directly leads to fatty liver and then to more advanced liver disease. Clinically, it’s been known for a long time that people who drink large amounts of alcohol habitually often have a fatty liver, which is fully reversible if they stop drinking, unless it has progressed to more advanced stages of liver disease. In observational studies, regular heavy drinking is associated with a higher liver fat content and an increased risk of fatty liver disease. And even among those who drink only small or moderate amounts of alcohol, there is some evidence of an association between the amount of alcohol consumed and the amount of fat in the liver. It is worth pointing out, however, that the evidence linking low to moderate alcohol consumption to an elevated liver fat content is weak and inconsistent. Some studies even suggest that moderate alcohol consumption may be protective against the development of a fatty liver. However, in observational studies, there is concern that those in the control group who do not consume any alcohol tend to be more likely to have obesity, are more metabolically unhealthy, and are more likely to have a history of alcohol abuse, all of which may be confounding the relationship between moderate alcohol consumption and liver fat content. Still, it is fair to say that it remains uncertain to which degree moderate drinking of alcoholic beverages plays a role in the development of fatty liver disease.
Lastly, independent of the total amount of alcohol consumed, another variable that is associated with liver fat content is the frequency of binge drinking.
So even though we don’t have the gold-standard type of evidence for alcohol, which would be large long-term randomized controlled trials looking at different doses and types of alcoholic beverages and their effect on liver fat content, the evidence we do have does strongly suggest that regular heavy drinking can pretty substantially lead to fat accumulation in the liver and fatty liver disease, while more moderate consumption plausibly has either no or a less substantial impact on liver fat content.
So that’s the impact of alcoholic beverages on liver fat content. How about sugar-sweetened beverages?
The data are very clear here as well. In observational studies, people who consume the most sugar-sweetened beverages have a much higher risk of developing fatty liver disease than people who do not drink sugar-sweetened beverages. And this is consistent with extensive experimental data from both animal models and humans showing that the regular consumption of sugar-sweetened beverages causes an increase in the fat content of the liver. Of note, in animal models, diets that are high in both fat and fructose most reliably create a non-alcoholic fatty liver disease that resembles the human condition. And, vice versa, people who have fatty liver and reduce their consumption of sugar-sweetened beverages experience a reduction in their liver fat content as a result (a limitation here is that these interventions also aimed to reduce the consumption of added sugar in solid form, i.e., these were not just focused on reducing sugar-sweetened beverage consumption).
Now, why is it that drinking sugar-sweetened beverages increases the fat content in the liver?
Again, the number 1 factor is clearly that sugar-sweetened beverages induce a calorie surplus and weight gain. But as with alcoholic beverages, there does seem to be an additional mechanism on top of that.
Beverages that contain sugar include sodas, lemonades, energy drinks, fruit juices, and fruit drinks. These contain either natural sugar, from fruit, or added sugar. If it’s added sugar, it’s either sucrose, normal household sugar, which consists of 50% glucose and 50% fructose, or high-fructose corn syrup, the most common version of which contains 45% glucose and 55% fructose (see figure below). If the source of the sugar is fruit, as in fruit juices or fruit drinks, then the natural sugar in the drink is also a mixture of mostly glucose and fructose. How much fructose and how much glucose depends on the type of fruit used to make the juice, but usually, it’s around half glucose and half fructose.
So, let’s say you drink a can of some kind of lemonade. One can may contain around 45g of sugar, and let’s estimate that’s 20 g of glucose and 25 g of fructose. And you are thirsty and gulp it all down in just a few minutes. The sugar is absorbed quickly into your bloodstream, so let’s look at the changes in blood glucose and fructose concentrations. If you are glucose tolerant, as we have discussed in prior blog posts, your blood sugar would start from a baseline of under 100 mg/dL, and a typical blood sugar response may look like the one shown in the figure below. Maybe topping out at 140 mg/dL. As we discussed in the blog post on the regulation of blood sugar, the glucose will mostly be taken up into muscle cells and fat cells.
The blood fructose concentrations, however, only increase from a baseline of around 5 mg/dL to a peak of around 8 or 10 mg/dL. Way, way lower than blood concentrations of glucose. And that is even though we consumed a beverage that contains more fructose than glucose. Right? Our lemonade contained 25 g of fructose, but at a peak blood fructose concentration of 10 mg/dL, and assuming we have about 6 liters of blood, we would never have more than 0.6 g of fructose in all of our blood. So, the body does seem to make a major effort to keep blood fructose levels very, very low. Why that is the case is not entirely clear, but one potential explanation is that fructose is a lot more reactive than glucose. As I have mentioned in the past, glucose attaches itself to proteins, in a process called glycosylation. And the glycosylation of proteins can change the biological function of these proteins, which is not usually a good thing. Fructose does the same, but it’s a lot more potent than glucose in doing so. By some estimates 10 times more potent, and this could explain why the body tries very hard to keep peripheral blood fructose levels extremely low.
How exactly the body does this is not entirely clear. It is likely that the liver removes much of the fructose right after it has been absorbed. Again, remember, once the glucose and fructose from our lemonade have been absorbed, they enter the portal vein, which passes the liver before entering the general blood circulation. And when glucose enters the liver, most of it passes through, while most of the fructose is taken up into liver cells.
Recent experiments in mice also suggest that the intestines and the gut microbiome play key roles in metabolizing fructose even before it enters the portal vein, thereby protecting the liver against excess dietary fructose. In mice, as much as 90% of all ingested fructose may never reach the liver as fructose, instead being oxidized or being metabolized to glucose, lactate, glyerol, or fatty acids. It is not known to which degree these findings from animal studies reflect the handling of fructose by humans. However, it is known from human tracer studies that some dietary fructose is converted to fatty acids already in the intestines. All we can say so far is that likely through a combination of fructose uptake and metabolism in the intestines and the liver, peripheral blood fructose levels are kept extremely low at all times. And it is also clear that the liver has to handle a substantial amount of fructose in people consuming large amounts of fructose.
And what does the liver do with fructose? Well, the problem is that the liver cannot store fructose. The liver cells can burn fructose for energy, or the fructose can be converted to glucose, lactate, or fat. And burning fructose for energy reduces the need to burn fat for energy, so if that happens, then fat oxidation is inhibited, which would be expected to temporarily raise the liver fat content. Similarly, the liver can convert fructose to fat, which would also raise the liver fat content (see figure below). So in a way, both alcohol and fructose have three things in common: both are preferentially taken up by the liver, and in the liver, both inhibit fat oxidation, and both can also be directly converted to fat by the liver cells.
As an aside, there are a few studies that have directly compared beverages sweetened with 100% fructose vs. 100% glucose. Again, even though no one drinks such beverages sweetened with just fructose or just glucose, using these types of sweeteners in a research study can be useful to try to figure out which of the two sugars plays the primary role in increasing weight gain or the fat content in the liver. As I discussed earlier, fructose- and glucose-sweetened beverages do not differ in the degree to which they trigger an overconsumption of calories or weight gain. However, fructose-sweetened beverages do increase de novo lipogenesis, i.e., the amount of fat synthesized by the liver, while glucose-sweetened beverages do not. This difference in the handling of fructose and glucose led to massive differences in metabolic health in one landmark study: drinking four servings per day of a 100% fructose-sweetened beverage induced all features of the metabolic syndrome in as little as 10 weeks, while an identical dose of 100% glucose-sweetened beverages did not in spite of similar weight gain. Specifically, dietary fructose-, but not glucose-sweetened beverages induced an increase in hepatic de novo lipogenesis, visceral fat mass, insulin resistance, and dyslipidemia characterized by massively elevated diurnal plasma triglyceride levels. Fructose, as compared to starch (glucose) is also able to induce an increase in the fat content of the liver even under isocaloric, weight-stable conditions. Still, two small, short, randomized controlled trials comparing the impact of fructose- versus glucose-sweetened beverages have not been able to detect differences on liver fat content. It is possible that these studies were too small or too short to detect differences; it is also possible that the previously detected differences in the effect of fructose versus glucose on de novo lipogenesis do not necessarily translate to greater liver fat content on diets rich in fructose versus glucose. While some uncertainties remain as to whether fructose indeed has a greater impact on liver fat content than glucose, the cumulative evidence would suggest that the fructose content of common sugar-sweetened beverages plays a particular role in the increase in liver fat content simply because fructose is the sugar that preferentially ends up in the liver and there can be converted into fat while also inhibiting an important pathway through which the liver can get rid of fat, fat oxidation (see figure below).
Lastly, let me clarify one important issue. Whenever you hear about fatty liver disease, clinicians usually make a distinction between alcoholic fatty liver disease and non-alcoholic fatty liver disease. These are basically the same conditions, but in non-alcoholic fatty liver disease, the patient doesn’t drink enough alcohol to fully explain the development of a fatty liver. I personally do not like this distinction very much. Both of these conditions are primarily, in the initial stage, characterized by excessive fat accumulation in the liver. There are a number of factors that affect fat accumulation in the liver, and excessive calorie intake, alcohol, sugars and particularly fructose in beverages are all among them. There are a few others that we will discuss in a separate blog post about fatty liver disease. But the key take-home message here is that these are all risk factors, and I would encourage you to think about these not as mutually exclusive, but as contributing to the disease together. In other words, if a person who is a habitual alcohol drinker also consumes two or three sugar-sweetened soft-drinks every day, do they really just develop an alcoholic fatty liver? Or isn’t it likely that the soft drinks contribute as well? And similarly, an average adult who gains, say 2 pounds per year and who regularly consumes moderate amounts of regular soda and, say, beer, will eventually develop fatty liver disease not because of one triggering factor, but because of this combination of several moderate exposures that lead to the gradual accumulation of fat in the liver over time. They may be diagnosed with NON-ALCOHOLIC fatty liver disease (NAFLD), but is it really fair to say that alcohol consumption didn’t play a role here?
Impact of Sugar and Fructose from Solid Foods on Liver Fat Content
So, naturally, many of you will wonder whether eating a lot of sugar and fructose from solid foods such as sweets, cakes, cookies, donuts, muffins, or even fruit and berries could similarly trigger fatty liver. We will talk about this in more detail in future blog posts, but my short response is that if someone consumes a lot of fructose from these solid foods, the fructose content may contribute to the fat content of the liver IF that person is in a state of chronic caloric excess and weight gain. In other words, if you chronically overeat on candy, cookies, and cake, and gain weight as a consequence, the weight gain itself could contribute to accumulation of fat in the liver, and the fructose content of these foods would be expected to also contribute. However, the data are pretty clear that all of these sugar- and fructose-rich solid foods are not nearly as bad as sugar-sweetened beverages, both in terms of their impact on excess calorie intake and weight gain, and almost certainly also in terms of their impact on liver fat content. While we currently do not have any randomized trials directly comparing the impact of sugars/fructose in liquid vs. solid form on liver fat content, the impact of an equal amount of sugar in solid form will almost certainly be smaller than that of a sugar-sweetened beverage because of the less pronounced/absent impact of sugar from solid foods on total calorie intake. I certainly do not want this to be understood as an endorsement of eating sugary foods in solid form; I still think they should be limited. I’d rather like what I am saying to be understood as a statement that I believe that sugar-sweetened beverages are even worse than other poor foods, and that strongly limiting our consumption of sugar-sweetened beverages is one of the most important things we can do for our health.
Now, a few specific words about whole fruit and berries. I mentioned that a high intake of sugar and fructose from solid foods could be problematic IF the overall calorie intake is chronically high and we gain weight. A particular benefit of fruit and berries is that these are very low in energy density, meaning calories per gram, and they have a lot of fiber. Both of these attributes make it hard to overeat calories on fruit or berries, and I personally would therefore not be concerned about fruit or berries. That is also informed by all of the evidence out there, from observational studies as well as randomized controlled trials, that link higher fruit and berry intake to a reduced risk of weight gain and obesity as well as chronic diseases, including metabolic diseases such as type 2 diabetes. I have actually authored a review paper on this very issue in which we found the relationship between fruit intake and metabolic disease to be either protective or neutral, with no consistent evidence suggesting that fruit intake increases the risk of obesity or metabolic disease. Let me state this clearly, because there is a lot of misinformation and confusion about this topic: I know of no good evidence linking greater consumption of fruit and berries to a higher risk of fatty liver disease, insulin resistance, or type 2 diabetes.
Summary and Conclusions
The regular consumption of alcoholic and sugar-sweetened beverages is a bit of a metabolic double whammy.
First, drinking these caloric beverages leads to an increase in calorie intake, which over time leads to weight gain in those drinking these beverages regularly. As we’ve discussed in prior blog posts, any weight gain raises the possibility that not all of the extra body fat can be stored in the subcutaneous fat tissue, which I consider the only safe storage location for fat in the human body. If the subcutaneous fat tissue is filled to capacity, this leads to increased flux of free fatty acids to the liver and muscle tissues, and an increase accumulation of fat in these ectopic fat depots, as well as the visceral fat depot surrounding the inner organs.
Second, regular consumption of both alcoholic and sugar-sweetened beverages is a major risk factor for the accumulation of fat in the liver. This is thought to occur primarily because of the excessive calorie surplus these beverages induce, but also because alcohol and fructose are specifically removed from the blood by the liver, and both can be converted into fat while also inhibiting fat oxidation by the liver cells.
Taken together, these two effects of alcoholic and sugar-sweetened beverages make these a primary contributor to weight gain, the accumulation of fat in ectopic depots, and all of the downstream consequences of these, including low-grade chronic inflammation and insulin resistance. So anyone who wants to prevent or reverse weight gain, fatty liver, low-grade inflammation, or insulin resistance would do well to minimize their consumption of alcoholic and sugar-sweetened beverages. I think minimizing the consumption of alcoholic and sugar-sweetened beverages is one of the lowest pieces of fruit if you are serious about preventing or reversing insulin resistance.
Let me add that there are additional suggested mechanisms through which fructose may affect metabolic health, including effects through elevated uric acid synthesis, mitochondrial dysfunction, and leptin resistance. Both fructose and alcohol have also been implicated in changing the gut microbiome and increasing intestinal permeability. I decided not to go into all of that in this blog post, but rest assured that all of these issues will be addressed in future blog posts. Step by step, right?
How I Use this Information
You will not be shocked to hear that I believe very strongly in the prevention of chronic disease. But then, I also do believe in the enjoyment of life, and good food and a nice drink in friendly company are among the very enjoyable things in life. So, how do I balance the information I shared here with the desire to enjoy a nice drink every once in a while?
Well, I can say quite honestly that I never drink sugar-sweetened beverages such as soda, energy drinks, or such. I just never got into the habit, and don’t feel compelled to start now.
I do very occasionally have a cold glass of apple juice diluted in sparkling water, which is wonderful on a cold summer day. And I do enjoy a glass of wine or some hard cider every once in a while (I have celiac disease, so I cannot drink most beer). In an average week, I may have zero to three of these drinks, and that is adding up the juice and the alcoholic drinks. But to me, I am not super strict about this, and there have probably occasionally been weeks when I had more than three drinks. I am just trying to be mindful and see alcoholic beverages as special treats for special occasions, and not to develop a regular habit.
So one suggestion I have for you is to examine if there is something you do regularly, such as always having soda in the fridge, tempting you to have some, or having a glass of wine with every dinner, or maybe you have a couple of beers while watching TV every night. Or you get drunk once per week, every week. Either of these would put you at risk of developing fatty liver along with insulin resistance.
If I HAD a fatty liver, or if my fasting triglycerides were higher than 150 mg/dL (>1.7 mmol/L) or my HOMA-IR greater than 2.5, or if I had type 2 diabetes, I would probably not have any alcoholic or sugar-sweetened beverages, ever. That’s me, and not everyone will want to be so strict, but I thought I’d share my thoughts about this as a way of helping you think this through for yourself.
As always, please feel free to post a comment below if you have any questions or comments. And if you’d be willing to do me a favor, please share this content with anyone you think may be interested.
Thank you for reading. Take care!
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9 Responses
Mario, thank you very much for the article!
It seems very obvious that sugar can make anyone fat and sick, but many people cannot understand and accept it. They think of fat and diseases as of natural process of ageing. Sad.
Thanks for sharing all that knowledge, Mario 👌👍
I tried several times to post the following comment, which might be of interest to your audience, on your YouTube video, but it kept disappearing, so I’m posting it here.
The study “The Small Intestine Converts Dietary Fructose into Glucose and Organic Acids” conducted by Cholsoon Jang’s lab at UC Irvine shows that “the small intestine clears most physiological doses of fructose even before fructose reaches the liver. Only high fructose doses overwhelm the intestine’s capacity, resulting in fructose spillover to the liver and also to the colonic gut microbiome. Such spillover causes excessive fatty acid synthesis in the liver and gut dysbiosis.”
The study can be accessed at https://www.cell.com/cell-metabolism/fulltext/S1550-4131(17)30729-5?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1550413117307295%3Fshowall%3Dtrue
An overview is available on the Jang Lab website (https://sites.uci.edu/janglab/):
“There are numerous associations between foods and diseases (e.g., the link between soda drinking and fatty liver). In most cases, however, the causality is elusive or underlying mechanisms are controversial. This problem likely originates from our incomplete understanding of how nutrients are processed in our body. One example is the metabolism of dietary fructose, a risk factor for obesity, diabetes, and fatty liver. Based on gene expression, it was believed that the liver is the sole site of fructose breakdown. However, our recent works showed that the small intestine clears most physiological doses of fructose even before fructose reaches the liver. Only high fructose doses overwhelm the intestine’s capacity, resulting in fructose spillover to the liver and also to the colonic gut microbiome. Such spillover causes excessive fatty acid synthesis in the liver and gut dysbiosis. Now, we study how fructose and other nutrients such as dietary fibers or alcohol interacts with and worsens/prevents systemic disorders (diabetes, obesity, fatty liver) and liver cancers.”
Best,
Stephane
Hi Stephane,
Thank you. Yes, that is a very nice paper. One problem I have with this is that it’s based on experiments in rodents, and we don’t have any data to tell us to which degree this applies to humans, as far as I am aware. Do you know of a similar paper in humans?
There are tracer studies in humans investigating the metabolic fate of fructose, but they only look at that in response to a single meal, which may be quite different from what happens with chronic overconsumption.
I’ll try to find some time to add a paragraph about the issue of fructose processing by the intestines to the blog post, as I do agree it’s important, and shouldn’t totally be ignored. It is also well possible that I overstated the importance of the liver in keeping peripheral blood fructose levels low, as the rodent data suggest that it’s primarily the intestines and secondarily the liver.
Interesting stuff. Thank you for bringing this up. And not sure why your comments on YouTube are disappearing; that’s concerning. I usually see all comments, and haven’t seen one of yours.
Cheers
Mario
Stephane,
I have now included a short discussion of the intestinal metabolism of fructose. I do think there is uncertainty as to how the mouse data translate to humans. Mice and humans are similar in a lot of ways, but our response to foods tends to differ, often substantially, simply because we evolved on very different diets and also because we have such different body weights. To my knowledge, there are no human studies that have investigated the role of the intestines and the gut microbiota in fructose catabolism. My best guess, partly also informed by human tracer studies, is that the intestines to catabolize fructose also in humans; to which degree this is practically relevant is anyone’s guess.
Best,
Mario
Thanks for your feedback, Mario. No, I’m not aware of any study on intestinal metabolism of fructose conducted on humans neither.
On the YouTube comment posting issue, I’ve got that once on another channel. I made a Google search and I’m definitely not the only one facing that problem. What is really odd is that it is not consistent : most of the times the comments get posted and from time to time they won’t.
Best,
Stephane
Hi Mario,
Thanks as always for your high quality and evidence forward content.
I understand that excess of highly processed food/drinks that are very palatable, especially sweetened drinks, can add to incremental calories very easily and lead to weight gain.
However, alcohol can suppress spikes in blood glucose (I don’t understand the mechanics of how/why this happens and have not been able to find a reference that explains it clearly and simply enough for me to understand)
For people with glucose spikes, say something like reactive hypoglycemia, what’s the harm on balance of having a moderate amount of wine for the occasional meals with higher sugar content that helps to head off the glucose spike so long as their overall weight is managed and they do not have fatty liver? In other words, is there a use case of moderate alcohol to prevent glucose spikes that can be a strategic lever.
Thanks
Hyeyeon
Hello Hyeyeon,
It’s a reasonable question. And it certainly comes down to personal choice.
To be sure, one or even two drinks occasionally are not a huge worry. However, I would not recommend using alcohol to suppress blood glucose levels, for one reason: if you have blood glucose spikes or even chronically high blood glucose levels, that’s when you would want to ‘use’ alcoholic drinks to suppress the blood glucose level. But particularly then, would I personally want to minimize any factors that make my glucose intolerance and determining factors, such as liver fat content, worse. I think the risk here is that we convince ourselves that the wine or beer is good for us, and many of us will embrace such reasoning to have a few drinks every night.
So, to me, alcoholic drinks are in a category I’d call ‘treats’, and just like other treats, I’ll have them and enjoy them, but only occasionally and in small doses. For the simple reason that excessive regular consumption clearly has negative consequences, and I don’t want to develop a regular habit. You certainly know yourself best, both in terms of your health and your ability to enjoy in moderation.
Cheers
Mario
Thank you for the excellent information. Several breweries are now producing zero-alcohol beer, my question is would a zero-alcohol beer be substantially better than a beer with alcohol? This is assuming only 1 beer is consumed.
Beer, even zero-alcohol beer, still contains sugars, but yes, I would assume it’s a bit better than regular beer.