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Serum Vitamin A and RBP
Some thoughts on Serum Vitamin A, and the fluctuating levels of RBP.
Vitamin A is released into the blood for a number of reasons. One, it is typically released in higher amounts when there is a higher viral load, infection, or illness. Vitamin A is an especially good weapon, but if there is no buffer, there will be collateral damage, and other cells will be damaged. This would theoretically also cause greater detox symptoms if the body has large stores of Vitamin A.
My main concern is how to slow the release of Vitamin A into the serum in order to reduce detox symptoms. Most digested Vitamin A will reach body stores. Whether they arrive in the organs or in fatty tissue, they will be safely stored. Vitamin A obviously becomes problematic when it is released in excessive amounts into the blood. One reason probably has to do with excessive consumption of preformed Vitamin A, and betacarotene for some. Another problem is related to having too much visceral fat, which will produce more RBP.
If Vitamin A is being absorbed, some of it needs to replace the Vitamin A that is already in the liver, organs, and fat. In order to do so, the liver needs to dump the Vitamin A that is already in the organs to make room for the fresh supply. This will be particularly present in people who have low fat stores and a poor ability to generate fat. When the body has no new fatty tissue to store the Vitamin A and no room in the liver, then the organs will likely dump existing Vitamin A, and make room for the new Vitamin A. With excessive Vitamin A consumption, you end up having a build up, and excessive release. This is also exasperated by an unhealthy diet. Someone posted a higher diet showing that Vegetable Oils caused RBP to increase more than butter. Not saying that is good, but obviously certain food items encourage more Vitamin A to be released, that seems to be independent of the Vitamin A content of the food.
Some questions I've been thinking about: What is causing more Vitamin A and RBP to be released into the blood? Also under what circumstances is Vitamin and RBP more or less harmful in the body?
The first study:
Effects of carbohydrate-containing and carbohydrate-restricted hypocaloric and eucaloric diets on serum concentrations of retinol-binding protein, thyroxine-binding prealbumin and transferrin
Abstract
The effects of diet on the serum concentrations of albumin, transferrin, thyroxine-binding prealbumin (TBPA) and retinol-binding protein (RBP) were studied in 3 groups of obese subjects (Groups I–III) and 1 group of normal weight subjects (Group IV). Group I subjects ate either a 830 kcal carbohydrate-containing diet (CCD) or carbohydrate-restricted diet (CRD), Group II and III subjects ate a hypocaloric CRD. Subjects in Group IV ate a eucaloric CRD. Serum albumin concentrations did not change in any of the 4 groups. Only the subjects in Group II had a statistically significant decrease in serum transferrin concentration 6 wk after starting the hypocaloric, CRD. Group I individuals eating the CRD and the subjects in Groups II, III and IV had significant decreases in the serum concentrations of TBPA and RBP after 1 wk which persisted without further change during the remaining 3–5 wk of the diets. Group I subjects eating the CCD had a significant decrease in TBPA concentration at 1 and 6 wk. The RBP serum concentration was significantly decreased after 1 wk on the diet, but was not significantly different from the control diet period at 6 wk. The magnitude of the decreases in serum concentrations of TBPA and RBP in the Group I subjects eating the CRD were significantly greater than in the Group I subjects eating the CCD. Thus, ingestion of a hypocaloric, CRD by obese individuals results in decreased serum concentrations of TBPA and RBP. Isocaloric substitution of carbohydrate for fat reduces this effect. Dietary carbohydrate apparently modulates the serum concentrations of TBPA and RBP, independently of caloric intake, since ingestion of a eucaloric CRD by normal weight individuals also decreased the serum concentration of the two visceral proteins.
If you wondering what diet these people were fed, and whether the low carb or high carb diet were high in Vitamin A, it doesn't matter, because both groups were supplementing Vitamin A:
All subjects in these studies ingested supplemental amounts of vitamin A (10,000 I.U./day), and there were no changes in bowel habits except for occasional mild constipation; it seems very unlikely that a defi- ciency of vitamin A was responsible for the lowered concentrations of RBP in serum.
Also, it unlikely has nothing to do with reduced Protein intake, as something else is coming into play:
Thus it appears that the observed changes in RBP and TBPA were unlikely to be the result of a reduction in whole body protein synthesis.
From this study it seems like CHO has a direct effect on the production of Retinol Binding protein, independent of caloric intake and protein intake.
RBP protein is a marker associated with a number of inflammatory illnesses.
Retinol Binding Protein 4 in Relation to Diet, Inflammation, Immunity, and Cardiovascular Diseases1
Abstract
Retinol binding protein 4 (RBP4), previously called retinol binding protein (RBP), is considered a specific carrier of retinol in the blood. It is also an adipokine that has been implicated in the pathophysiology of insulin resistance. RBP4 seems to be correlated with cardiometabolic markers in inflammatory chronic diseases, including obesity, type 2 diabetes, metabolic syndrome, and cardiovascular diseases (CVDs). It has recently been suggested that inflammation produced by RBP4 induces insulin resistance and CVD. The clinical relevance of this hypothesis is discussed in this review. Knowledge concerning the association of RBP4 with inflammation markers, oxidative stress, and CVDs as well as concerning the role of diet and antioxidants in decreasing RBP4 concentrations are discussed. Special attention is given to methodologies used in previously published studies and covariates that should be controlled when planning new studies on this adipokine.
"RBP4 has been known as a negative acute phase inflammatory reactant. Yang et al. (10) indicated that RBP4 was a novel adipokine and that its concentrations are elevated in insulin-resistant states associated with obesity and type 2 diabetes (T2D). Several other studies observed high concentrations of RBP4 in obesity (11–15) as a chronic inflammatory state and in its complications including T2D (16–20), metabolic syndrome (21–27), and cardiovascular diseases (CVDs)"
My point in all this, is that you shouldn't exclusively consider the Vitamin A content of the food you are eating. There is obviously other factors involved. The release of Vitamin A into the serum happens all the time. Yet certain biological circumstances encourage more Vitamin A to be released. I posted a study earlier that showed oranges were more effective at raising retinol levels than green vegetables and carrots, despite having a much lower Vitamin A content. Eventually, I researched a bit further, and found this study:
Consumption of fructose- but not glucose-sweetened beverages for 10 weeks increases circulating concentrations of uric acid, retinol binding protein-4, and gamma-glutamyl transferase activity in overweight/obese humans
RBP-4
No previous studies have investigated the effects of glucose or fructose consumption on circulating levels of RBP-4. There is increasing evidence suggesting that RBP-4 may be an important link between increases of visceral adiposity and insulin resistance [32]. In animal studies RBP-4 has been clearly shown to reduce glucose uptake and impair insulin signaling in muscle, as well as to increase hepatic glucose production via induction of the gluconeogenic enzyme phosphoenolpyruvate carboxykinase (PEPCK) [17]. In humans, increases of circulating RBP-4 are strongly associated with insulin resistance in adipose tissue [33], and elevations of circulating RBP-4 are predictive of a diagnosis of metabolic syndrome [34]. While hepatocytes are the primary source of RBP-4, it has been demonstrated that adipocytes can also contribute significantly to circulating concentrations of RBP-4 [35]. Reduced expression of the insulin-stimulated glucose transporter, GLUT4, in adipocytes has been shown to lead directly to increased adipocyte secretion of RBP-4 [33]. Moreover, expression of RBP-4 in humans is significantly greater in visceral adipose tissues (VAT) compared with subcutaneous adipose tissue (SAT) and is associated with an increase of adipocyte size [16].
ASIDE: This is interesting because fructose is notorious for increasing visceral fat, which is know to be very harmful.
Circulating RBP-4 concentrations are significantly elevated following 10 wks of fructose consumption (Table 2) and these changes are correlated with increases of postprandial TG (Table 3, Figure 3). We have hypothesized that fructose consumption can promote reductions in insulin sensitivity by providing substrate for hepatic DNL leading to hepatic triglyceride accumulation, PKC activation, and increased hepatic insulin resistance [7] and have suggested that this mechanism is responsible for the reductions in insulin sensitivity previously reported in these same subjects [6]. Although the reported increases of RBP-4 were relatively modest, our results suggest the possibility that fructose-induced increases of RBP-4 levels may also have contributed to the previously reported reductions of insulin sensitivity in these subjects [6].
We have suggested that the differential effects of fructose and glucose on regional adipose deposition may be explained in part by the increased sensitivity of SAT relative to VAT to insulin-stimulated lipoprotein lipase (LPL) activation [6], and by our reported observations that insulin responses were decreased in subjects consuming fructose and increased in subjects consuming glucose [36]. The differential changes in RBP-4 levels in subjects consuming fructose or glucose are consistent with this mechanism considering that reductions of post-meal insulin exposure in subjects consuming fructose would lead to decreased expression of GLUT4 in adipocytes, which would be expected to be associated with an increase in the production and secretion of RBP-4 from adipose tissue (VAT in particular). Thus, it is possible that reduced insulin exposure in subjects consuming fructose led to increased plasma RBP-4 levels directly by decreasing expression of GLUT4 in adipose tissue, and indirectly by increasing deposition of TG into VAT, leading to increased visceral adipocyte size, and increased secretion of RBP-4. The significant reduction of circulating RBP-4 concentrations observed in subjects consuming glucose-sweetened beverages is consistent with the observations that glucose consumption did not result in increased DNL, postprandial hypertriglyceridemia, accumulation of VAT or reduced postprandial insulin exposure [6].
The finding that increases of RBP-4 during fructose consumption were larger in men than in women was not unexpected considering that TG responses and increases of VAT deposition were also considerably greater in men [6] (Figure 2). We have also reported that women exhibited greater decreases in insulin sensitivity than men in response to fructose consumption, and have hypothesized that this may be due to decreased rates of VLDL production and secretion, leading to larger increases of hepatic lipid [6]. Our findings suggest that the increased rate of VLDL production/secretion following fructose consumption in men is accompanied by an increase of RBP-4 levels. These elevations of RBP-4 levels are likely the result of increased accumulation of VAT and decreased insulin-stimulated GLUT4 expression in adipocytes. These data suggest that in men fructose consumption likely contributes to increases of hepatic insulin resistance both directly by providing substrate for hepatic DNL leading to increased hepatic TG accumulation and decreased hepatic insulin sensitivity [7], and indirectly by increasing visceral adiposity [37], while in women it is primarily a direct effect mediated by increased hepatic DNL and lipid content.
There are multiple ways for Vitamin A to be problematic, regardless of whether you consume it at all. If you consume a diet that is high in fructose, you may increase visceral fat around your organs, which will make Vitamin A problematic if you happen to eat it again, as your body will produce more RBP. Additionally, an excessive reduction in fat intake makes Vitamin A more problematic, because there are no lipids to buffer any retinol in the serum.
What's the takeaway from all of this? Eat lower carbs? Go keto? Eat more butter? Less vegetable oil?
Too confusing to draw conclusions. Who knows what's better? Go through the detox once and for all or keep some fat (and therefore some VA) coming in. I don't know but then again nobody really tried going low VA for long term
Quote from Guest on December 27, 2018, 9:55 pmWhat's the takeaway from all of this? Eat lower carbs? Go keto? Eat more butter? Less vegetable oil?
Too confusing to draw conclusions. Who knows what's better? Go through the detox once and for all or keep some fat (and therefore some VA) coming in. I don't know but then again nobody really tried going low VA for long term
There is no take-away. I am still experimenting, and am trying not be dogmatic about a particular diet. This is not meant to be about a particular diet. I am merely raising observations from reading some papers, and hoping others contribute some information or observation. I have felt some benefits from reducing Vitamin A, and eliminating Beta Carotene from my diet. At the same time, I think the cyclical "detox" symptoms that may be related to something else. It could be that another storm is brewing, that is unrelated to Vitamin A. So I'm going to keep a skeptical hat on and continue to read about this. I recommend paying attention to your body. Its needs aren't static.
I think this is exactly the right approach. We aren’t going to be able to draw any firm conclusions without experimentation on larger scales then we are going to achieve until there is more interest and more people willing to participate. We can get ideas from studies, and interpret other studies based on our experiences, but it would be a mistake to try to draw conclusions based on incomplete information.
That doesn’t mean we shouldn’t try to understand what these types of studies mean, it just means we have to be open minded, and willing to reconsider our positions from time to time when the evidence isn’t consistent with our results.
The thing that does seem to be working, for many of us, anyway, is to significantly reduce “vitamin”-A consumption long term. If we can find short-cuts,” that help eliminate “vitamin “-A quicker and/or more safely, then that would be great, but it will take some time to sort it all out.
So far, I don’t think there are any experts on “vitamin”-A depletion. I don’t think Grant would consider himself an expert, even though he has the most experience. He is very cautious about making recommendations or claiming to know much more than his basic premise, proven repeatedly in experiments, that excess “vitamin”-A is toxic, and his observation that it doesn’t appear to be essential at all, based on his self-experimentation, and his own small-scale animal studies.
I an very skeptical of people who claim to know more than this. They are probably jumping to conclusions based on very limited information that may or may not turn out to be accurate in the end. That doesn’t mean we shouldn’t try some or all of there ideas, but don’t stick to a “protocol” that isn’t working for you.
Also, it is worth considering that there may be different ways of “detoxing” that might be more appropriate for some circumstances than others. Some people seem to want to deliberately want to slow the detoxification process to reduce side effects. Others may be willing to put up with side effects to detox faster. Your context might not be the same as mine. Additionally, we don’t know, and may not know for a very long time whether a fast detox with side effects (if this actually happens, which is conjecture at this point) may cause any irreversible damage or if it would allow for faster healing overall.
Anyway, long story short, nutrition and biology are very complex. Don’t try to draw conclusions from one or two studies. Cause and effect and context can easily be confused (for example, does high RBP indicate more “vitamin”-A is being released, or that the body is better able to eliminate it, and could it mean one thing in one context and another in a different context?).
I’ve been trying to improve my health through diet for a very long time, and have tried a number of different approaches, and the biggest takeaway I’ve had, is that certainty and dogmatism are the enemies of knowledge, and open-mindedness and doubt are its allies. Good luck everyone!
Well said Guest 😀 Lots of questions to be answered as this whole experiment progresses. Open-mindedness & doubt are allies of knowledge. Love that.
Jenny
I'm feeling like fructose is causing problems for me. On days when I eat more sweet snacks, I feel worse.
I think I will try some glucose syrup as a sweetener instead of table sugar to see if it makes a difference. Another solution is to cut sweets and go with starchy snacks like popcorn, bread and chips.
Quote from Guest on December 28, 2018, 9:30 amI think this is exactly the right approach. We aren’t going to be able to draw any firm conclusions without experimentation on larger scales then we are going to achieve until there is more interest and more people willing to participate. We can get ideas from studies, and interpret other studies based on our experiences, but it would be a mistake to try to draw conclusions based on incomplete information.
That doesn’t mean we shouldn’t try to understand what these types of studies mean, it just means we have to be open minded, and willing to reconsider our positions from time to time when the evidence isn’t consistent with our results.
The thing that does seem to be working, for many of us, anyway, is to significantly reduce “vitamin”-A consumption long term. If we can find short-cuts,” that help eliminate “vitamin “-A quicker and/or more safely, then that would be great, but it will take some time to sort it all out.
So far, I don’t think there are any experts on “vitamin”-A depletion. I don’t think Grant would consider himself an expert, even though he has the most experience. He is very cautious about making recommendations or claiming to know much more than his basic premise, proven repeatedly in experiments, that excess “vitamin”-A is toxic, and his observation that it doesn’t appear to be essential at all, based on his self-experimentation, and his own small-scale animal studies.
I an very skeptical of people who claim to know more than this. They are probably jumping to conclusions based on very limited information that may or may not turn out to be accurate in the end. That doesn’t mean we shouldn’t try some or all of there ideas, but don’t stick to a “protocol” that isn’t working for you.
Also, it is worth considering that there may be different ways of “detoxing” that might be more appropriate for some circumstances than others. Some people seem to want to deliberately want to slow the detoxification process to reduce side effects. Others may be willing to put up with side effects to detox faster. Your context might not be the same as mine. Additionally, we don’t know, and may not know for a very long time whether a fast detox with side effects (if this actually happens, which is conjecture at this point) may cause any irreversible damage or if it would allow for faster healing overall.
Anyway, long story short, nutrition and biology are very complex. Don’t try to draw conclusions from one or two studies. Cause and effect and context can easily be confused (for example, does high RBP indicate more “vitamin”-A is being released, or that the body is better able to eliminate it, and could it mean one thing in one context and another in a different context?).
I’ve been trying to improve my health through diet for a very long time, and have tried a number of different approaches, and the biggest takeaway I’ve had, is that certainty and dogmatism are the enemies of knowledge, and open-mindedness and doubt are its allies. Good luck everyone!
Fortunately or unfortunately Dr. Smith might now have the greatest insight into what is working best for people as far as vA detox. I don't have complete faith in him though and it costs alot to have him tell you how to undo some of the damage he directed in the first place. Still he has access to lots of peoples feedback on the vA diet and things that seem to help or make it worse and he is doing his best now to look into vitamin A (wish he had done just 5% of that when he directed people to take liver, vA supplements and eat color if it seemed to *agree* with them) Maybe Harry M is observing trends in his clients as well?
Quote from Guest on January 5, 2019, 7:27 pmQuote from Guest on December 28, 2018, 9:30 amI think this is exactly the right approach. We aren’t going to be able to draw any firm conclusions without experimentation on larger scales then we are going to achieve until there is more interest and more people willing to participate. We can get ideas from studies, and interpret other studies based on our experiences, but it would be a mistake to try to draw conclusions based on incomplete information.
That doesn’t mean we shouldn’t try to understand what these types of studies mean, it just means we have to be open minded, and willing to reconsider our positions from time to time when the evidence isn’t consistent with our results.
The thing that does seem to be working, for many of us, anyway, is to significantly reduce “vitamin”-A consumption long term. If we can find short-cuts,” that help eliminate “vitamin “-A quicker and/or more safely, then that would be great, but it will take some time to sort it all out.
So far, I don’t think there are any experts on “vitamin”-A depletion. I don’t think Grant would consider himself an expert, even though he has the most experience. He is very cautious about making recommendations or claiming to know much more than his basic premise, proven repeatedly in experiments, that excess “vitamin”-A is toxic, and his observation that it doesn’t appear to be essential at all, based on his self-experimentation, and his own small-scale animal studies.
I an very skeptical of people who claim to know more than this. They are probably jumping to conclusions based on very limited information that may or may not turn out to be accurate in the end. That doesn’t mean we shouldn’t try some or all of there ideas, but don’t stick to a “protocol” that isn’t working for you.
Also, it is worth considering that there may be different ways of “detoxing” that might be more appropriate for some circumstances than others. Some people seem to want to deliberately want to slow the detoxification process to reduce side effects. Others may be willing to put up with side effects to detox faster. Your context might not be the same as mine. Additionally, we don’t know, and may not know for a very long time whether a fast detox with side effects (if this actually happens, which is conjecture at this point) may cause any irreversible damage or if it would allow for faster healing overall.
Anyway, long story short, nutrition and biology are very complex. Don’t try to draw conclusions from one or two studies. Cause and effect and context can easily be confused (for example, does high RBP indicate more “vitamin”-A is being released, or that the body is better able to eliminate it, and could it mean one thing in one context and another in a different context?).
I’ve been trying to improve my health through diet for a very long time, and have tried a number of different approaches, and the biggest takeaway I’ve had, is that certainty and dogmatism are the enemies of knowledge, and open-mindedness and doubt are its allies. Good luck everyone!
Fortunately or unfortunately Dr. Smith might now have the greatest insight into what is working best for people as far as vA detox. I don't have complete faith in him though and it costs alot to have him tell you how to undo some of the damage he directed in the first place. Still he has access to lots of peoples feedback on the vA diet and things that seem to help or make it worse and he is doing his best now to look into vitamin A (wish he had done just 5% of that when he directed people to take liver, vA supplements and eat color if it seemed to *agree* with them) Maybe Harry M is observing trends in his clients as well?
Harry is and he had been quite helpful for me. I couldn’t afford to consult with Dr. Smith (working minimally while studying for boards) and Harry and I had been emailing so I took the plunge and started working with him. Having someone knowledgeable to collaborate with one on one has been very helpful.
Good to know! Does he provide a folder of info like Smith does?
Quote from Guest on January 6, 2019, 5:15 amGood to know! Does he provide a folder of info like Smith does?
He gave me a vitamin A folder. I’m not sure what Dr. Smith gives clients by comparison but I’m happy with the information and support Harry has provided. Bella