Update 83: High Fructose, Vitamin D, & Oxidative Stress
本文由‘中国推动’学者、江南大学药学院石漱新同学编辑整理。
MedcCram.com. Welcome to another MedMram COVID-19 update.
And we’re at an interesting time in terms of where we are globally. For there are some countries in areas where the viral pandemic is winding down. In other areas where there’s a lockdown things are opening up. In certain other areas, there is a resurgence or a surge and so really depending on where you are and in what country or in what part of the country are in and even whether you’re in a city
or a suburb, you could have a different story. And so it’s really important for you to pay attention to what’s going on locally to find out exactly what it is that’s going on.
In terms of vaccines, there is an update there with the Johnson & Johnson stage. They say here that on June 10th, Johnson & Johnson announced that it’s accelerating phase 1/2 trials for its vaccine candidate and that human trials will begin in the second half of July. That’s just next month instead of
September of 2020 as originally planned. You may remember that Johnson & Johnson was one of the top five selected for Operation Warp Speed, so we will be keeping an eye on them.
I wanted to continue where we left off in the last video talking about vitamin D. And I wanted to remind you all of what evidence is come out in terms of research. And we came up with a slide that summarizes it nicely. And what we’ve got down here at the bottom is oxidative stress in the form of superoxide, which is a reactive oxygen species. And what we believe is going on here is when SARS-Covid-2
Infects the cell and takes out the ACE2 receptor. ACE2 is no longer able to convert Angiotensin-II to Angiotensin-1,7. And that’s important because Angiotensin-II does promote the production of superoxide, which is not a good thing. What we also see is that Angiotensin-1,7 inhibits the production of superoxide, which is a good thing. When you knock out ACE2, that doesn’t happen
and you get more of this. In addition to that, SARS-Cov-2 virus itself causes a predilection for increased PMNs, which are basically neutrophils. And neutrophils also give off superoxide. And this is important because when you have an increased amount of oxidative stress, and that’s the key word there, that can cause issues.
So again, what are those issues? SARS-Cov-2 leads to decrease ACE2 because that’s the receptor that it hits, increasing Angiotensin-II, decreasing Angiotensin-1,7, increasing superoxide. And that superoxide causes an oxidative stress, which causes issues with endothelial cell dysfunction, these are the cells that cover the vasculature, increasing release of Von Willebrand’s factor, leading to thrombosis. And thrombosis can cause issues in the lungs.
It can cause issues with oxygenation and we’ve seen the autopsies in the New England Journal of Medicine report about a month ago that showed that SARS-Cov-2 patients had 9 times the amount of clots in the lungs over control groups, for instance, with influenza virus in their lungs. So bearing this in mind, specifically oxidative stress is very important. And the reason why it’s important is because if this
virus is going to give you a burst of oxidative stress, it’s the people who don’t have oxidative stress in the first place that are going to be better able to tolerate that kind of a hit. And as is evidenced by the number of patients and the type of patients that were seeing ending up in the hospital with COVID-19, (they are) not the patients that we thought that was going to be, not the patients with chronic lung disease, not the patients with COPD, although there are those patients.
No, instead what we are seeing is we’re seeing patients with elevated BMIs. These are overweight patients, patients with kidney disease, patients with cardiovascular disease, diabetes. As we showed you last time, it was the patients with normal hemoglobin A1Cs but increased glucose that were almost 10 times more likely to have problems with SARS-Covid-2. With that in mind, we’re going to embark on a journey
into what else can we do to prevent the negative effects of coronavirus.
And up to this point, we have talked about things that you could take. We have talked about zinc, N-acetylcysteine, vitamin D, vitamin C. We’ve talked about the supplements in our update number 59. What I’d like to do is, for the first time, let’s talk about things that we are taking into our body that may not be helpful. Now, I recognize
this is a completely different discussion. And we need to stick to the evidence and see whether or not it makes sense to analyze these things.
Okay, so we’re going to talk about fructose and this paper was published three years ago in the journal Nutrients. And I think it’s an excellent reference article in terms of fructose and what it does in terms of obesity and oxidative stress. And it’s titled “Fructose Consumption in the Development of Obesity and the Effects of Different Protocols of Physical
Exercise on the Hepatic Metabolism”. So first of all, what is fructose? Fructose is basically a six carbon sugar. The one that we typically see in our body is D-fructose, which is the mirror image of L-fructose.
When you take fructose here on the right and couplet with glucose here on the left, the combination of these two that are linked gives you something called sucrose. And all of these things are naturally occurring sugar compounds that you’ll see in cane sugar, in fruits and things of that in nature. However, what we’ve decided to do in terms of manufacturing, especially in the United States, but also in other countries, is to make high concentrations of fructose called high fructose corn syrup and
other types of fructose. And put it into foodstuffs and have those eaten. So the question is what does fructose do to animals and to human beings in terms of oxidative stress. So let’s investigate that since we’ve always thought here at MedCram that oxidative stress may play an important role in the body’s ability to fight coronavirus.
So in this article, it ties fructose consumption
with obesity and weight gain and this article is really a compendium of a lot of different articles and references. So I thought it was a very good reference to have if anyone is interested in learning more about this. As they say here, “The present study is characterized as a narrative literature review.” Now, notice what it says here under animal evidence, “as previously discussed the rates of obesity and fructose consumption are following the same pattern; thus, several studies were conducted to understand how
fructose consumption was related to weight gain. In an experiment in which rodents were fed fructose or sucrose”, remember that sucrose contains both fructose and glucose, “during 8 weeks, the author’s observed that even though there were no differences between the total caloric intake, animals fed fructose gain more weight than those fed sucrose”, remember that sucrose is a 50% combination of glucose and fructose. So therefore on a per weight basis, sucrose would have half the amount of
fructose than fructose does itself. It also goes on says, “In the same study, when the intervention period lasted 6 months, male and female rodents fed fructose had an accumulation of adipose tissue mainly in the abdominal area and an increase in serum triglyceride levels.” And this is exactly what we know in medicine as not a good pattern of fat distribution. Now watch this very carefully, “Moreover, several studies corroborated with the evidence that high fructose consumption might lead to
accumulation of adipose tissue, systemic inflammation, obesity and oxidative stress, and consequently insulin resistance in different tissues.” and their references for all of that. “Furthermore, mice who receive fructose in their water had an elevation of serum proteins with proinflammatory activity, such as interleukin 1β, interleukin-6”, by the way, interleukin-6 is directly implicated in coronavirus, in fact, one of the medications that’s being used, Tocilizumab, is an
IL-6 inhibitor. We move on, “and tumor necrosis factor alpha. Rodrigues and colleagues demonstrated that the replacement of sucrose for fructose in one meal was enough to establish inflammation in the liver and in adipose tissue. In addition, one hour after intervention, tumor necrosis factor alpha levels of those fructose fit animals were higher than those sucrose fed animals, and this raised remained for at least four hours.” They move on to a nice figure here. That
shows the effects of fructose on metabolism of the cell and also a metabolic diseases. Interesting point here, it says, “finally reactive oxygen species generated by fructosylation increases oxidative damage and stress response in the inner of the cell, leading to DNA damage and postinflammatory cytokine production.
They go on to say in this article that exercise can actually reverse some of the oxidative stress, as they mentioned here, at least in rodents. They summarize their findings here in figure 2 where they talk about a fructose rich diet which causes hyperinsulinemia, oxidative stress, pancreatic beta-cell exhaustion and then finally diabetes, and these are the people that we’re seeing that are affected by COVID-19 in the hospital. Reduction in energy expenditure, obesity
, adipocyte hypertrophy and inflammation. Lipid spillover going to increase the LDL, decreased HDL, which leads to peripheral insulin resistance, hepatic steatosis and finally diabetes. And folks, this is exactly what we were talking about in the last update in terms of elevated glucose found in these patients when they came into the hospital. This is exactly the type of pathways that we’re seeing in COVID-19. And it apparently shows that physical exercise can re
verse a lot of what we’re seeing here in terms of fructose rich diets.
Here’s another study going back to 2011 published in the Annals of the New York Academy of Sciences. and it’s titled “Fructose consumption: Recent results and their potential implications”. So we’ve known this for a while even dating back 10 years or more.
They say here that recent data suggests that fructose consumption and human results in increased visceral, lipid dysregulation and decrease insulin sensitivity, all of which have been associated with increased risk for the very things that we’re seeing in our COVID-19 patients, cardiovascular disease and type 2 diabetes.
So here’s an interesting article that was published in Global Public Health back in 2012, and it’s an interesting article because they look at high fructose corn syrup and diabetes country by country. Here’s the abstract, “the overall aim of the study was to evaluate, from a global and ecological perspective, the relationships between availability of high fructose corn syrup, HFCS, and the prevalence of type 2 diabetes using published resources,
country-level estimates with an n = 43 different countries were obtained for: total sugar, high fructose corn syrup and total calorie availability. Obesity, two separate prevalence estimates for diabetes, prevalence estimates for impaired glucose tolerance and fasting plasma glucose.” They use different correlations and what it was that they found was that diabetes prevalence was 20% higher in countries with higher availability
of HFCS, what I mean by that is that there are certain laws and restrictions about how much high fructose corn syrup can be put in the products in that country. And so they looked at the availability of that. And when they did that, it was 20% higher in countries with higher availability compared to countries with low availability. And these differences were retained or strengthened after adjusting for country-level estimates of body mass index, population and gross domestic product. And that was statistically significant
with a p-value of 0.03; fasting plasma glucose=5.34 vs. 5.22 mmol/L. Again, that is a European adjustment of glucose. The p-value they’re also statistically significant at 0.03. And this was despite similarities in obesity and total sugar and calorie availability. So what does that mean? Despite the fact that all of these things are the same. It
seems as though the availability of high fructose corn syrup increases the amount of diabetes. And these results suggest that countries with higher availability of high fructose corn syrup have a higher prevalence of type 2 diabetes independent of obesity.
And when you looked into that article of the different countries, the country that was at the top for use of high fructose corn syrup was, you guessed it, the United States, 24.78 kilograms per year per person. As opposed to in most of the European countries, especially the eastern European countries that I reviewed in the article, it was around zero because they don’t allow high fructose corn syrup. I will give you the link to the article. However, the next
thing that I found regarding fructose was mind-blowing, especially given the fact that we have just talked about COVID-19 and vitamin D levels and how essential vitamin D may play a role in terms of good health immunity and potentially fighting COVID-19.
First of all, though, you’ve got to understand exactly how Vitamin D is metabolized in your body. Either you can get it from the sun or from a pill form, but you’re going to get a basic vitamin D level and this vitamin D level, cholecalciferol, if you will, is the product that is in route ready to be used with some modifications that still need to happen. The first modification is 25 hydroxylase, which occurs in the liver and that converts the vitamin D
into 25 hydroxy vitamin D. But it’s still not in its active form, only until it gets hydroxylized again at the one position. So 1-hydroxylase, which occurs in the kidney will now convert your vitamin D to the active form that it can be used which is 1,25-dihydroxy vitamin D. There is another enzyme called 24 hydroxylase, which will take either 25 or 1,25-dihydroxy vitamin D and
convert it to an inactive form, in this case, 24,25 dihydroxy-vitamin D or 1,24,25 hydroxy-vitamin D. So now you know the metabolism. So if you’re not getting enough sun, you can take a pill supplement and that will get you enough raw material vitamin D, floating around in your body ready for activation. So that your body can regulate how much vitamin D that you need.
So now you understand that let’s move on to the next step.
Well, here’s an interesting article that was published in 2013 in the American Journal of Physiology-Endocrinology and Metabolism, “Excessive Fructose Intake Causes 1,25-(OH)(2)D(3)-dependent Inhibition of Intestinal and Renal Calcium Transport in Growing Rats”. So what do they say here? They say, “we recently discovered that chronic high fructose intake by lactating racks prevents adaptive increases in rates of active intestinal
transport. And in levels of 1,25-dihydroxy vitamin D”, that’s the active form of vitamin D, “since sufficient calcium absorption is essential for skeletal growth. Our Discovery may explain findings that excessive consumption of sweeteners compromises bone integrity in children. We tested the hypothesis that 1,25”, which is the active form, “mediates the inhibitory effect of excessive fructose intake on active calcium to transport.” What they found was that
dietary fructose increase the expression of 24-hydroxylase and decrease that of 1α-hydroxylase.
So in other words, the enzymes that are responsible for moving product away from this assembly line toward the active form, was increased by fructose and the final product that finally put that 1-hydroxylase, so that 1-hydroxy on the number one carbon to make that active form, was inhibited by high fructose.
So essentially, fructose or high levels of it, we should say, stimulated
the breakdown of vitamin D and it’s active metabolites and inhibited the final activation phase in the kidney to make the active form that you need for your body, which is 1,25-dihydroxy vitamin D.
And they found the significant for the same reason that I find it significant, saying that because of the large amounts of fructose now consumed by Americans specifically, increasingly vulnerable to calcium and vitamin D deficiency.
Here is another article put out by the same group a year later in 2014. And it’s titled “Chronic
High Fructose intake Reduces Serum 1,25 (OH)2D3 Levels in Calcium-Sufficient Rodents”. What they found was that over a three-month period of time of feeding them a high fructose or glucose diet with normal calcium levels, there was a reduction in dihydroxy-vitamin D.
Here’s another article that was published another year later in 2015 by a different group published in the Iranian Journal of medical Sciences.
And interesting, they looked at a compound very similar to n-acetyl cysteine for which we were talking about previously, called S-methyl cysteine. It’s a hydrophilic cysteine containing compound. So it still has the SH part of it and found in garlic and onions. And then wanted to see whether or not this substance could protect against oxidative stress, which is what we’ve been talking about in COVID-19. So, what was it that they did to induce this metabolic syndrome or this
oxidative stress. They fed these rats a high fructose diet.
60% fructose was used for 8 weeks and then they used this substance called S-methyl cysteine and a dose of 100 milligrams per kilogram per day per rat in the study. The fasting glucose, insulin, insulin resistance and tumor necrosis factor alpha and erythrocyte enzymatic antioxidants were measured. And what they found was interesting, “Increased levels of plasma glucose, insulin, malondialdehyde, tumor necrosis
factor-alpha and insulin resistance and decreased levels of glutathione, glutathione peroxidase and catalase were found in rats on the high fructose diet.”
Remember in some of our previous lectures that we talked about these systems of the body has in place to get rid of oxidative stress, like catalase, glutathione peroxidase, superoxide dismutase. These are some of the very things that they’re talking about here that are reduced in this high fructose diet.
However, this oral administration of SMC for 60 days resulted in a significant attenuation of plasma glucose, insulin, tumor necrosis factor-alpha, insulin resistance and improved antioxidant enzyme activities. And of course we’ll put all of these studies links in the description below.
So think about this the next time you go to the supermarket to pick up food. Look at the ingredient list and see whether you see fructose.
And as you’re taking your vitamin D, think about whether or not fructose is actually working against your vitamin D. Now, remember we don’t have randomized controlled data with fructose and COVID-19. We have a bunch of data that looks at laboratory values, animal studies, population studies. So we
can’t say this for absolute sure but we do know that there are some definite studies that show that fructose does affect the metabolism of vitamin D in ways that may be negative. And the United States is a big consumer of high fructose. And I love to hear your comments regarding this issue.
Thanks for joining us.
Add comment