I began researching vitamin D, the immune system and HCV. I came up with some interesting stuff....
Presented in October 2008 at the 73rd Annual Scientific Meeting of the American College of Gastroenterology, researchers from the University of Tennessee in Memphis measured the vitamin D levels in people with chronic liver disease. Of those evaluated, 85 percent of the study participants had chronic Hepatitis C. After dividing every vitamin D deficiency into three categories (mild, moderate and severe), the investigators found the following:
· 92.4 percent of those with chronic liver disease had some degree of vitamin D deficiency
· At least 33 percent of participants were severely deficient in vitamin D
· Severe vitamin D deficiency was more common among those with cirrhosis
Vitamin D is metabolized by the liver and is converted to 1,25 dihydroxyvitamin D3 which is the active form of the vitamin.
Those with impaired liver function can have poor conversion from Vitamin D3 into 1,25 dihydroxyvitamin D3 or any of its other biologicaly active metabolites. 1,25 dihydroxyvitamin D3 has been found to have an immunological role. 1,25(OH)2D3 seems to modulate immunity principally via regulating T-cell function. Vitamin D Receptor (VDR) has been found to be expressed on virtually every type of cell involved in immunity. The immunomodulatory actions of vitamin D are elicited through its direct action on T-cell and antigen-presenting cell (APC) functions. Thus, 1,25(OH)2D3 may have an important physiologic role in immunoregulation. When vitamin D is deficient or signals through the VDR are weakened, Th1 cell actions are intensified, whereas regulatory T cells and Th2 cells are diminished, thus favoring an autoimmune Th1 response. This is a proinflammatory response.
Persistent (HCV) infection upsets the balance between immunostimulatory and inhibitory cytokines which can prolong inflammation and lead to necrosis, fibrosis, and chronic liver disease.
It is well known that people of African descent are less likely to respond to standard treatment. Is this due to the fact that higher melanin levels block UV light from penetrating deep enough into the skin to create Vitamin D? Darker skin is darker due to higher melanin content.
It is well known that people of African descent are less likely to respond to standard treatment. Is this due to the fact that higher melanin levels block UV light from penetrating deep enough into the skin to create Vitamin D? Darker skin is darker due to higher melanin content. Do non-responders suffer from low levels of Vitamin D (or more specifically 1,25 dihydroxyvitamin D3)? Can increasing the levels increase response and SVR?
Will higher vitamin D levels result in higher percentages of SVR?
A clinical trial is underway in Isreal to determine whether Vitamin D will improve response rates to treatment.: Clinical trials website study number NCT00804752.
I also found these interesting results that show the Th1/Th2 ratio is important to SVR....
The study enrolled 120 chronic hepatitis C patients with HCV genotype 1 and a high baseline HCV RNA level -- both predictors of poor response -- who started 48-week combination therapy using pegylated interferon alpha-2b (PegIntron) plus ribavirin.
54 of 120 patients (45) achieved sustained virological response (SVR), or continued undetectable HCV RNA 6 months after completing therapy.
In a logistic regression analysis, the pre-treatment factors significantly associated with SVR were:
ISDR mutation (odds ratio [OR] 86.0; P = 0.0008];
Th1 to Th2 ratio < 15.5 (OR 9.6; P = 0.0021);
Body weight of 59 kg;
Neutrophil count of 2300 cells/mL.
Employing a logistic regression model using these 4 factors to estimate SVR before starting therapy, patients fell into 3 groups when plotted according to estimated and actual SVR rates:
High sensitivity group: actual SVR rate 91% (32 of 35);
Intermediate sensitivity group: actual SVR rate 41% (15 of 37);
Low sensitivity group: actual SVR rate 15% (7 of 48).
Rapid or early virological responses were seen in 80% of high sensitivity patients who achieved SVR, but in only 40% of intermediate or low sensitivity patients
Null and very late virological responses were rare in the high sensitivity group.
In conclusion, the researchers wrote, "a logistic regression model that includes the sequence of ISDR of the HCV, Th1/Th2 ratio, body weight, and neutrophil count can be useful for accurately predicting actual SVR rate before combination therapy."
Vitamin D is a fat soluble vitamin and is not easily excreted from the body through urine as water soluble vitamins, rather fat soluble vitamins (A, D, E, and K) are usually stored in the body, liver, and muscles when consumed in excess. There could also be a toxicity concern with fat soluble vitamins:
"Dr. Vieth suggests that critical toxicity may occur at doses of 20,000 IU daily and that the Upper Limit (UL) of safety be set at 10,000 IU, rather than the current 2,000 IU. While this may or may not be the definitive marker for safety in healthy persons with no active LIVER or kidney disease, there is no clinical evidence that long-term supplementation needs to be greater than 4,000 IU for optimal daily maintenance. This level would be somewhat lower when combined with exposure to UV-B.3;76"
i just wouldn't really take the risk. i'm sure milk is fine, just don't go overboard with supplements.
for what it's worth, when I asked my hepatologist if there any vitamins I should take other than a multi-, the only vitamin that he mentioned was vitamin D. Not sure if he mentioned specifically for the liver, but obviously is bullish on it, and I now take it daily
I take Vit D supplements under the direction of my endocrinologist. If you are taking the sups AND getting regular blood tests to check your D levels and verify that the sups are needed and working then I think it's a good thing. My joint achiness went away when she put me on the Vit D (and I'd been thinking it was the Hep--not).
She did say that milk is not the best way to get Vit D. I'm on liquid drops of D3.
i take Stresstabs:
Serving Size: 1 Tablet
Servings Per Container: 60
Amount per Serving % Daily Value
Vitamin C (from Ester-C calcium ascorbate) 250 mg 417%
Vitamin E (as dl-Alpha Tocopheryl Acetate) 30 IU 100%
Thiamin (B1) (as Thiamine Mononitrate) 10 mg 667%
Riboflavin (B2) 10 mg 588%
Niacin (B3) 100 mg 500%
Vitamin B6 (as Pyridoxine Hydrochloride) 5 mg 250%
Folate,Folic Acid,Folacin 400 mcg 100%
Vitamin B12 (as Cyanocobalamin) 12 mcg 200%
Biotin 45 mcg 15%
Pantothenic acid (as d-Calcium Pantothenate) 20 mg 200%
Calcium 70 mg 7%
Phosphorus 30 mg 3%
Zinc (as Zinc Oxide) 23.9 mg 159%
Copper (as Cupric Oxide) 3 mg 150%
* Daily Value not established.
but my hepa also recommended in conjunction with Protegra, which i'm scared to take bc of the huge amount of Vitamin A it contains:
Serving Size: 1 Softgel
Servings Per Container: 60
Amount per Serving % Daily Value
Vitamin A 100% as Beta Carotene 5000 IU 100
Vitamin C (as Ascorbic Acid) 250 mg 417
Vitamin E (d-Alpha Tocopheryl Acetate) 60 IU 200
Zinc (as Zinc Oxide) 7.5 mg 50
Selenium (as Sodium Selenate) 15 mcg 21
Copper (as Cupric Oxide) 1 mg 50
Manganese (as Manganese Sulfate) 1.5 mg 75
Standardized Grape Seed Extract (85%-95% proanthocyanidins) 50 mg*
* Daily Value not established.
I am scheduled for labwork tomorrow and one of the tests is for a Vit. D level. I cannot be out in the sunlight because of skin issues, so that's out for me for a way to get Vit. D. I have to drink Lactose free milk on my cereal and coffee because of Lactose intolerance, but it has Vit. D added to it. I do eat yogurt though. I'll be interested in seeing what it shows.
my primary tested me about 2 years ago and found my vitatmin D level low, so now i take 1,000 iu. ithe doc said that he has patients that work out of doors here in sunny colorado and have low levels of D. he also ran the spectracell test, something HR recommends, and found my zinc levels were low.
"Will vitamin D do the same?"
By itself....No. HCV patients lack many other micronutrients. According to "The Impact of Diet on Liver Fibrosis and on Response to Interferon Therapy in Patients With HCV-Related Chronic Hepatitis", HCV patients also lack Vitamin E and Riboflavin (Vit B 2).
But the main thing is that they lack Glutathione....look at the recent SAMe and Betaine studies (SAMe is used to make glutathione). They replaced those two things and people SVR'd. They also lack B12. There's a new study from AASLD that showed that higher levels of B12 werre associated with SVR.
"It is well known that people of African descent are less likely to respond to standard treatment. Is this due to the fact that higher melanin levels block UV light from penetrating deep enough into the skin to create Vitamin D? "
That's hilarious. Blacks fail because they're INSULIN RESISTANT.
From the Gomez-Romero study....
"Thus, insulin resistance emerges as the most important host factor in the prediction of response in non-diabetic patients treated with the best available option -peginterferon plus ribavirin. Interestingly, insulin resistance has been found a common denominator to the majority of features associated with difficult-to-treat patients. Patients with cirrhosis, obesity, HIV coinfection and AFRO-AMERICAN showed all insulin resistance.
"I also found these interesting results that show the Th1/Th2 ratio is important to SVR"
The immune system is basically divided into two functions - humoral response (including the antibody response), and the cytotoxic response.
A strong cytotoxic response is required for the elimination of the virus. In all patients who have spontaneously cleared the virus, there is documented evidence of a strong cytotoxic response.
The problem is that even if Vitamin D was to help, you will still be injecting interferon and sometimes interferon overstimulates interleukins on the wrong side of your immune system, and understimulates the genes needed for a strong cytotoxic response.
>>"It is well known that people of African descent are less likely to respond to standard treatment. Is this due to the fact that higher melanin levels block UV light from penetrating deep enough into the skin to create Vitamin D? "
>That's hilarious. Blacks fail because they're INSULIN RESISTANT.
Vitamin D is well known to help prevent type 2 diabetes.
Perhaps low levels of Vitamin D leads to insulin resistance and later to diabetes.
Perhaps Vitamin D improves insulin function??
The insulin resistance caused by HCV is actually hepatic hyperglycemia (it's not the same as the simple antagonism of PPAR gamma of adipose tissue and skeletal muscle associated with Type 2 diabetes). In some people, HCV causes the liver to disgorge huge amounts of glucagon and the pancreas has to produce more insulin to control it (eventually, the extra work damages the pancreatic B cells. A fasting blood sugar (basal reading) above 100 is a sign of hepatic hyperglycemia and the resulting hyperinsulinemia.
Let's look at the areas where Vitamin D may help:
1. Pancreatic B cell function:
The direct effect of Vitamin D may be mediated by binding of its circulating active form to the pancreatic B-cell Vitamin D receptor.
The indirect effect of vitamin D comes from its role in regulating extracellular calcium and calcium flux through the cell. Insulin secretion is a calcium-dependent process; therefore, alterations in calcium can have adverse effects on cell secretory function. So inadequate calcium intake or Vitamin D insufficiency may alter the balance between the extracellular and intracellular cell calcium pools, which may interfere with normal insulin release, especially in response to a glucose load (as in after a meal).
(And remember that oxidative stress leeches calcium....and Vitamin D helps absorb calcium. So if you're low in one, it makes sense that you'd be low on the other. I forgot to mention that according to the study titled "The Impact of Diet on Liver Fibrosis and on Response to Interferon Therapy in Patients With HCV-Related Chronic Hepatitis" , people with HCV were also low in calcium).
Vitamin D supplementation improved insulin release in some but not all randomized trials.
2. Insulin resistance:
Calcium is essential for insulin-mediated intracellular processes in insulin-responsive tissues such as skeletal muscle and adipose tissue. And as I mentioned, Vitamin D has a role in regulating extracellular calcium and ensuring normal calcium influx through cell membranes and adequate intracellular calcium. So theoretically, a lack of either can result in peripheral insulin resistance.
Some randomized trials on the effect of vitamin D and/or calcium supplementation on insulin resistance showed no effect while others showed improvement of insulin action.
Vitamin D may improve insulin sensitivity and promote cell survival by modulating the generation and effects of cytokines....but the data is still limited and conflicting.
Vitamin D appears to affect exclusively the insulin response to glucose stimulation, whereas it does not appear to influence basal insulinemia. In other words, it will help in some areas, but not the hepatic hyperglycemia.
"Perhaps Vitamin D improves insulin function??"
Yes, it does. So supplementing it if your level is low (along with calcium) might help.
"Vitamin D is well known to help prevent type 2 diabetes.
Perhaps low levels of Vitamin D leads to insulin resistance and later to diabetes. "
But the insulin resistance in HCV is not caused by lack of Vitamin D. It's caused by oxidative stress, TNFa, etc.
But I like your thinking. Anybody who looks for ways of resolving IR is certainly on my team.
"The Role of Vitamin D and Calcium in Type 2 Diabetes"
Thank you for the articles. I just had my vitamin D level checked last week. The result was 46 ng/mL. Do you think this is high enough? I take 3,000 IU of D3 everyday and I get extra sun because I travel to South America several times a month. I am in week 6 of SOC + TMC435 /SOC + Placebo treatment.
In the study in Israel, it seems they tried to keep Vitamin D levels above 32ng/ml. (http://www.medscape.com/viewarticle/711902) .
One must remember though, that vitamin D is converted to an intermediate form in the liver (25 hydroxyvitamin D) , then to the active form (1,25 dihydroxyvitamin D) in the kidney.
I am unsure whether they were measuring vitamin D, 25-hydroxy or the 1,25-dihydroxy (or all three). The method for measuring was not mentioned so we can't be sure how accurate this number is (>32 ng/ml) or if the other forms influenced to count. Testing Vitamin D levels in people is relatively new. I am sure there are several differing techniques that can give differing results.
Looks like your results are the sum of the liver metabolite 25-hydroxy Vit D3 along with Vitamin D3 and Vitamin D2.
It says nothing of 1,25 dihydroxy vitamin D3 (the active form).
It may be lumped in there as well. Who knows.
Until a sensitive, specific (for the active form) standardized test comes along, test results can mean anything and nothing.
Careful with your 3,000 IU per day, might be a bit high. Check with your doctor.
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