March 2011 Hepatitis C Treated with Low Dose Naltrexone (LDN) - Dr. Zagon comments

Hepatitis C Viral load -  16,500 slightly up from the 14,679 that it was in October 2010.

ALT - 30 up from 24 in October  (6-40)

AST - 33 up from 31 in October  (10-35)


Basically the same as it has been for the last few lab tests!  Normal liver function tests and lower viral load using 3 mg. of Low Dose Naltrexone.

My platelets also went up as did my red blood cell count.  However, my IgA was back on the low side again - last labs, it was normal for the first time.

Ferritin was 43, which is down a bit from last.  Iron was also down as was total saturation.

I also saw my gastro recently and was pleasantly surprised with his attitude and manner. I had not seen him since 2009 shortly after starting LDN and he had yelled at me for taking it.

I had a new abdominal ultrasound done last week and got back the results.  The U/S report used the word unremarkable to describe most things - however, it showed "diffuse fatty infiltration of the liver" DRAT! My last u/s was done about 3-4 months following my appointment with Dr. Berkson in 2009 and my five IV ALA (alpha-lipoic-acid) treatments and it had "normal liver function" with no mention of fattly liver! Every other u/s that I have had since 2001 has had fatty something, but not the one after Dr. Berkson.  I do know that Dr. Berkson recommended a course of initial IV ALA treatments, then oral supplementation and then another round of IV ALA.  I have never had any more treatments since 2009.

So, maybe that is proof of the power of IV ALA - or as the gastro and I discussed, maybe interpreting ultrasounds is up to whoever reads it. But I would tend to think that the IV ALA did it - back in 2009 during the same time, my AFP (alpha feta protein) test went up to 6.1 (which was slightly above normal) - it had always been normal before. I remember reading at the time that liver regeneration can sometimes cause elevations in AFP. My doctor today told me that I was correct - "You have been reading". My AFP was normal for every test since then.

Fortunately for me, my own CAM doc here does ALA, so I will want to have a few. It'll probably be awhile though as I don't have the money for it now.

Anyway, it was a pleasant gastro visit - probably the only one that I've had since I was diagnosed in 2002.


NOTE!  2013 UPDATE ON DOSING - PLEASE READ POST:

Why 3mg. LDN might be best?

Back to original post:

Dr. Zagon's comments on LDN dosing

For my current labs,  I was taking the 3 mg. LDN every other night.  In the past, I had tried increasing the dosage and taking it almost every night.  Some folks in our Hepatitis Cam group had initial drops in their viral load and liver enzymes on 3 mg. but their levels seemed to go back up down the line.  When they increased their LDN dosage, their levels went back down.  I wrote to Dr. Zagon about this and this is what he said:

"You are a product of not understanding how LDN works - a classic example I might add. And most of your colleagues on the web share your misinformation.

LDN works through what is called the opioid growth factor - a native peptide (and its receptor) in your body. LDN is a decoy that fills in at the site of the receptor - the body not having the peptide makes more of it in compensation. Now the trick we discovered 30 years ago. A short time of naltrexone - low dose naltrexone is the term lay people use (but really intermittent opioid receptor blockade) increases the peptide. After the naltrexone is metabolized - optimal time is 4-6 hours for around 3 mg, the high levels of peptide and actually an increase in receptors as well can interact. This depresses cell/viral proliferation - and makes you better.

By increasing your dose of LDN you are cutting into the time you need for an optimal reaction. Hence - you feel problems.

My advice - take 3 mg/day. If you have a problem, start taking LDN once every 2 days (many folks are taking it that way - and
some every 3 days).

Dr. Zagon

A story. A lady calls me and says she has breast cancer. She is taking LDN and the cancer is growing more rapidly. I ask her how LDN is being given - she says that since LDN is so good, she is taking it several times a day. Now you know why she had a faster growing cancer - she was not allowing the opioid-receptor interaction to occur because of so much naltrexone.

And, if you block the receptors all day with naltrexone (high dose of naltrexone), we now see that wound healing is accelerated. Why, because the cells are speeding up in replication and healing the wound faster.

Below is what I wrote to Dr. Zagon:

I have been on 3 mg. LDN for over a year for my HCV with terrific results - viral load dropped from 1,400,000 to 11,200 on my April 2010 labs and lft's are normal. I was on 3 mg. every other night,then every night. I recently increased my dosage in an attempt to lower my viral load even more - went up to 3.5 and then to 4 mg. taking it every night. However, I have had small outbreaks of shingles and HHV2 on the 4 mg. dosage. I did not take the LDN for a couple of nights and started again last night at 3.5. I am going togo back to every other night dosing for now.

So after Dr. Zagon's first response, I wrote back to him and explained about our Hepatitis Cam group's database and how most folks lft's and viral load went down when they increased their LDN dosage.  This was his reply:

First, science is science. If these individuals are having to go up on dosage to evoke a positive response, that is potentially meaningful. My interpretation is that these patients are exhibiting a tolerance that builds to LDN. Very interesting. Our initial recommendation was 3-10 mg of LDN daily.

Second, your story does not conform to what others may be
seeing - tolerance. If anything, you are encountering a sensitivity. I would certainly try 3 mg every other day and see what happens.

Third, this entire LDN business is empirical right now -
you have to be in the frontier of just plain trying things out. In
your case, lower is the best. It may be that in some individuals
their pharmacology is far different than yours - they might be
building a tolerance and need more. Alternatively, the LDN is either breaking down over time and loses potentcy, or is not or high quality or is being mixed in with "fillers" that are negating the action of the LDN.


That correspondence took place over last summer (2010) - now, I ponder why my viral load seems to be staying the same (though slowly creeping higher) and not getting any lower, or thankfully, not skyrocketing back up to where it was pre-LDN - which was over 1 million.  What can I do to get it even lower?  So, despite what Dr. Zagon says, I am going to start taking the LDN every night and perhaps slightly increasing the dosage in an attempt to lower my viral load even more.  He has added a bit of confusion into the mix, I must say.   Or look into TLR's (Toll Like Receptors) - there has been a lot of research of late about them, particularly in HCV.  Dosing of LDN 2 x a day is also another possibility - I will update after more research.

Low Dose Naltrexone for Hepatitis C September 2010 Lab Work

I got back my full September lab results the other day.  I have been on 3 mg. LDN since March of 2009 for my Hepatitis C - I also test positive for Sjogren's and RA, though with few symptoms.  I have/had an IGA partial deficiency and in these labs, it is normal for the first time.  My doctor ( Dr. Kashi Rai) believes that my limited but strict gluten/dairy free diet has been the reason for the result.

I am thrilled that my HCV viral load is still quite low as are my liver enzymes - and that most of my other tests are pretty darn good!  After the hellish time I've had of it these past few months, along with Panda's illness and death on October 4th (St. Francis Blessing of the Animals day), and enormous, unrelenting financial and emotional stress, I was prepared for the tests to be terrible.   Oh, the power of LDN and DIET!

My liver enzymes are still all within normal levels with ALT (6-40)  at 24 from a pre-LDN level of 174  - AST (10-35)  at 31 from pre-LDN of 99


HCV viral load went up a tad from the 11,600 it was on my last labs to it's current 14,679.  Still a far cry from the pre-LDN 1,280,000 level!

I was also pleased with the overall Lymphocytes - which have all increased.

 
 
 

October 2010 LAB RESULTS

 Tests                          09/10            01/09

C-Reactive Protein                   0.10              0.10

Platelet (140-400)                     171               163

Glucose (65-99)                         84                84

BUN (7-25)                               10                 5

Creatinine (.060-1.10)              0.73              0.70

Sodium (135-146)                    138                135

Potassium (3.5-5.3)                   4.3                4.6

Protein total (6.2-8.3)               7.9                 8.9

Albumin (3.6-5.1)                     4.9                 5.2

Globulin (2.2-3.9)                     3.0                 3.7

 Bilirubin Total                          1.1                 1.1

Alk. Phos (33-130)                   59                 72

AST (10-35)                             31                 99

ALT (6-40)                               24                174

Cytomegalovirus IGG              2.60                2.36

CMV - IGM                          0.79                0.67

DHEA Sulfate (15-170)          106                  92


Epstein-Barr IGG                  1:320                1.320


Estradiol                                  19                   31


Ferritin (10-232)                      53                  115


HCV RNA -                       14,679                 1,280,000

Herpesvirus 6 IGG                1:10                   1.80

HHV6 IGM                          1.20                    1:20

IGF I - ECL                          185

IGF -I                                                            139

Immunoglobulin A (81-463)    95                    72


Immunoglobulin G (694-1618) 1377              1932


Immunoglobulin M (48-271)     93                 135


Lymphocytes

CD3 (Mature T cells) ( 57-85)   78                   77


Absolute CD3+ Cells (840-3060)  1441        1008


%CD4 (Helper Cells) (30-61)       57                 52


Absolute CD4+ cells (490-1740) 1067             720


%CD8 (Suppressor T Cells) (12-42)  22            22


Absolute CD8+ cells (180-1170)    405             333


Helper/Suppressor ratio (0.86-5.00)  2.59           2.17

%CD16+CD56 (4-25)                        6               10
(Natural Killer Cells)


Absolute NK Cells (70-760)              102            128
(CD16+CD56 Cells)


%CD19 (B cells) (6-29)                      15             12


Absolute CD19+ Cells) (110-660)     277             189

Absolute Lymphocytes (850-3900)    1857          1577


Progesterone                                         0.5             0.5


Rheumatoid Factor (<14)                      18           31


Sjogren's Antibody(SS-A) (<1.0)          2.8         4.5



T3, FREE (230-420)                              330             337


T4, FREE (0.8-1.8)                                1.0             1.3


TSH, 3RD GENERATION (0.40-4.50)  2.67        1.97


Testosterone Total                                    60            63

Vitamin D, 25-OH Total                            83           62



Also, I wanted to mention that the new 2010 edition of the free LDN book 'Those Who Suffer Much, Know Much' is now available via PDF. My Hepatitis C story is included in this year's edition as well as Joyce's HBV positive daughter's. Also has much more info about using LDN in other disorders as well as more about LDN in general:

LDN Research Trust

May 2010 Hepatitis C Labwork with Low Dose Naltrexone (LDN)

In March, 2009, I started taking Low Dose Naltrexone, or LDN to treat my Hepatitis C. It was initially prescribed to me by Dr. Burt Berkson at his clinic in Las Cruces, New Mexico, in 3 mg. capsules. Since that time, my own doctor writes my LDN refill prescriptions.


Within months, it brought down my viral load and normalized my liver enzymes. And on my most recent lab work (5/2010), my viral load is even lower.


Viral load at 11,300! In December, it was 34,524. September: 18,729. Pre-LDN Jan. 09 - 1,280,000


ALT: 25  December: 34  Sept. 36   Pre-LDN Jan. 09 - 174 (range: 6-40)

AST: 30 December: 31 Sept. 37 Pre-LDN Jan. 09 - 99 (range: 10-35)


My doctor uses Quest lab:

HCV RNA, PCR test result of 11,300 with a log of 4.05. It was the COBAS (R) Ampliprep/COBAS, TagMan (R) RNA Test Kit (Roche)



Will update complete labs soon!  Vitamin D at 95 from 53 after taking 5,000-10,000 of NOW Vitamin D3.

Low Dose Naltrexone (LDN) and the Liver

note - this post title really should be "Naltrexone and the Liver" as the studies below all are based on full strength naltrexone and not LDN.

Low Dose Naltrexone, or LDN, is an FDA approved medication.
"Naltrexone itself was approved by the FDA in 1984 in a 50mg dose for the purpose of helping heroin or opium addicts, by blocking the effect of such drugs. By blocking opioid receptors, naltrexone also blocks the reception of the opioid hormones that our brain and adrenal glands produce: beta-endorphin and metenkephalin."

Although naltrexone itself is an FDA-approved drug, the varied uses of LDN still await application to the FDA after related scientific clinical trials. LDN (in the 3mg or 4.5mg dosage) has not yet been submitted for approval because the prospective clinical trials that are required for FDA approval need to be funded at the cost of many millions of dollars.

Naltrexone is a prescription drug, so your physician would have to give you a prescription after deciding that LDN appears appropriate for you.

http://www.lowdosenaltrexone.org/

Many doctors will not prescribe LDN, as they are not aware that it is FDA approved and that various clinical trials for various disorders have been done or are in progress. The other reason is because of the "Black Box Warning" for full strength Naltrexone due to adverse liver effects on obese patients using 300mg.

Full-dose naltrexone (50mg) carries a cautionary warning against its use in those with liver disease. This warning was placed because of adverse liver effects that were found in experiments involving 300mg daily. The 50mg dose does not apparently produce impairment of liver function nor, of course, do the much smaller 3mg and 4.5mg doses.

Further studies have shown that LDN is actually beneficial to the liver in low doses - however, most of the studies done used much higher doses of Low Dose Naltrexone.

Study of hepatotoxicity of naltrexone in the treatment of alcoholism.
Since a black box warning was issued by the Food and Drug Administration regarding the use of the opiate antagonist naltrexone (NTX), many clinicians have been concerned about current labeling of the potential hepatotoxicity risk of NTX in the treatment of opiate dependence and alcoholism. Despite many reports that demonstrated that the use of NTX did not cause elevation of liver enzymes, controversy concerning whether NTX is hepatotoxic continues. The current study monitored 74 alcoholic patients who received 25mg of NTX daily in the first week and then 50mg of NTX daily for the rest of the 12-week period. After the 12-week treatment, levels of the hepatic enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST) did not show any elevation, except in one subject, and the results strongly support that NTX did not induce abnormalities in liver function tests or elevate the liver enzymes. Instead, a statistical significance of decreasing levels of ALT and AST in the liver was shown throughout the study. These findings provide further support that NTX is not hepatotoxic at the recommended daily dose and may be beneficial for patients with elevated liver enzymes.
PMID: 16839858 [PubMed - indexed for MEDLINE]

Effects of long-term treatment with naltrexone on hepatic enzyme activity.Mean plasma levels of hepatic enzymes did not show significant modification in the course of treatment with naltrexone.

PMID: 1686854 [PubMed - indexed for MEDLINE]
Naltrexone: report of lack of hepatotoxicity in acute viral hepatitis, with a review of the literature.
Many clinicians appear to be concerned about the potential hepatotoxicity of the opiate antagonist naltrexone (NTX) and this may be one reason why it is not used more widely in treating both heroin and alcohol abusers. Some much-quoted early studies noted abnormalities in liver function tests (LFTs) in very obese patients taking high doses, although there was no evidence of clinically significant liver dysfunction.

We describe a heroin abuser in whom clinical and laboratory manifestations of acute hepatitis B and C appeared a few days after the insertion of a subcutaneous naltrexone implant. A decision was made not to remove the implant but the hepatitis resolved completely and uneventfully well within the normal time-scale. A review of the literature indicates that even when given at much higher doses than are needed for treating heroin or alcohol abusers, there is no evidence that NTX causes clinically significant liver disease or exacerbates, even at high doses, serious pre-existing liver disease.

PMID: 15203443 [PubMed - indexed for MEDLINE]

Naltrexone protects against lipopolysaccharide/D-galactosamine-induced hepatitis in mice.
Results demonstrated that post-treatment with naltrexone (20 mg/kg, i.p.) significantly attenuated the deleterious liver function in mice treated with LPS/D-gal. It was also found that naltrexone significantly inhibited the elevation of plasma tumor necrosis factor-alpha (TNF-alpha) caused by LPS/D-gal. The overproduction of nitric oxide (NO) and superoxide anions induced by LPS/D-gal were also significantly reduced by naltrexone. Moreover, infiltration of neutrophils into the liver of mice 12 h after treatment with LPS/D-gal was also decreased by naltrexone. In conclusion, the beneficial effects of naltrexone on LPS/D-gal-induced hepatitis result from its inhibition of pro-inflammatory factors and antioxidant effects. Thus, naltrexone is of therapeutic potential for treating liver injury.

PMID: 19023176 [PubMed - indexed for MEDLINE

Lack of hepatotoxicity with naltrexone treatment.
In summary, chronic administration of naltrexone in doses up to 300 mg/day for periods up to 36 months does not significantly change hepatic function, as measured by SGOT and SGPT levels.

PMID: 7983232 [PubMed - indexed for MEDLINE]

Opioid receptor blockade reduces Fas-induced hepatitis in mice.

PMID: 15389866 [PubMed - indexed for MEDLINE]

Naltrexone, an opioid receptor antagonist, attenuates liver fibrosis in bile duct ligated rats.

CONCLUSIONS: This is the first study to demonstrate that administration of an opioid antagonist prevents the development of hepatic fibrosis in cirrhosis. Opioids can influence liver fibrogenesis directly via the effect on HSCs and regulation of the redox sensitive mechanisms in the liver.

PMID: 16543289 [PubMed - indexed for MEDLINE]

Opioid system blockade decreases collagenase activity and improves liver injury in a rat model of cholestasis.
CONCLUSION: Opioid receptor blockade improved the degree of liver injury in cholestasis, as assessed by plasma enzyme and liver MMP-2 activities. The beneficial effect of naltrexone may be due to its ability to increase liver SAM level and restore the SAM : SAH ratio.

PMID: 17295775 [PubMed - indexed for MEDLINE]

Effect of oral naltrexone on pruritus in cholestatic patients.

CONCLUSION: Naltrexone can be used in the treatment of pruritus in cholestatic patients and is a safe drug showing few, mild and self-limited complications.

PMID: 16534857 [PubMed - indexed for MEDLINE]

Opioid peptides and primary biliary cirrhosis.
Patients with liver disease have increased plasma concentrations of the endogenous opioid peptides methionine enkephalin and leucine enkephalin. As an initial investigation to determine whether opioid peptides contribute to any of the clinical manifestations of hepatic disease nalmefene, a specific opioid antagonist devoid of agonist activity, was given to 11 patients with cirrhosis. They all experienced a severe opioid withdrawal reaction on starting the drug. In the nine patients with primary biliary cirrhosis pruritus was greatly alleviated, fatigue seemed to improve, and plasma bilirubin concentration, which had been rising, showed a modest fall in all except one patient. These results indicate that blocking opioid receptors has an effect on some of the metabolic abnormalities of liver disease.

PMID: 3147046 [PubMed - indexed for MEDLINE]
Pharmacokinetics of long-acting naltrexone in subjects with mild to moderate hepatic impairment.

Long-acting naltrexone is an extended-release formulation developed with the goal of continuous naltrexone exposure for 1 month for the treatment of alcohol dependence. The influence of mild and moderate hepatic impairment on naltrexone pharmacokinetics following long-acting naltrexone 190-mg administration was assessed. Subjects with mild (Child-Pugh grade A) and moderate (Child-Pugh grade B) hepatic impairment (n = 6 per group) and matched control subjects (n = 13) were enrolled. Naltrexone and 6beta-naltrexol concentrations were determined over a period of 63 days following a single intramuscular dose. Naltrexone and 6beta-naltrexol concentrations were detected in all subjects through 28 days. Total exposure (AUC(0-infinity)) of naltrexone and 6beta-naltrexol was similar across all groups. The long apparent half-lives of naltrexone and 6beta-naltrexol (5-8 days) were attributed to the slow release of naltrexone (long-acting naltrexone exhibits absorption rate-limited elimination or "flip-flop" kinetics); elimination was not altered in subjects with hepatic impairment. Based on pharmacokinetic considerations, the dose of long-acting naltrexone does not need to be adjusted in patients with mild or moderate hepatic impairment.

PMID: 16239359 [PubMed - indexed for MEDLINE]

High-dose naltrexone and liver function safety.






























Studies have found naltrexone useful in the treatment of diseases other than opiate addiction in which endogenous opioids presumably play a role, such as alcoholism and eating disorders. Some of these studies involve high doses (100-200 mg bid). Because investigational studies with high doses (300 mg/day) reported clinically significant increases in liver enzyme levels, the authors measured a spectrum of liver function parameters in response to high doses of naltrexone in a double-blind, crossover trial (100 mg bid) followed by an open-label period (200 mg bid). They observed no adverse clinical or laboratory changes in liver function in association with high-dose naltrexone therapy in eating disorders.

PMID: 9097868 [PubMed - indexed for MEDLINE]

Effect of liver cirrhosis on the systemic availability of naltrexone in humans.

CONCLUSIONS: Our data suggest the occurrence of important changes in the systemic availability of naltrexone and 6 beta-naltrexol in liver cirrhosis; such alterations are consistent with lesser reduction of naltrexone to 6 beta-naltrexol and appear to be related to the severity of liver disease. This must be considered when administering naltrexone in conditions of liver insufficiency.
PMID: 9314128 [PubMed - indexed for MEDLINE]

Hepatic safety of once-monthly injectable extended-release naltrexone administered to actively drinking alcoholics.

RESULTS: There were no significant differences in alanine aminotransferase, aspartate aminotransferase, or bilirubin levels between the study groups at study initiation or at subsequent assessments. Gamma-glutamyltransferase in the XR-NTX 380 mg group was lower compared with placebo at weeks 4, 8, 12, and 20. Both high (>3 times the upper limit of normal) liver chemistry tests (LCTs) and hepatic-related adverse events were infrequent in all study groups. In patients who were drinking heavily throughout the study, obese subjects, or those taking nonsteroidal anti-inflammatory drugs, there was no increase in frequency of high LCTs or hepatic-related adverse events in patients receiving XR-NTX (either dose) compared with placebo. CONCLUSION: Extended-release formulation of naltrexone does not appear to be hepatotoxic when taken at the recommended clinical doses in actively drinking alcohol-dependent patients.

PMID: 18241321 [PubMed - indexed for MEDLINE]

Changes in transaminases over the course of a 12-week, double-blind nalmefene trial in a 38-year-old female subject.










A gradual return to normal in ALT and AST, while treatment with nalmefene continued, does not support the role of nalmefene as an hepatotoxin. Relapse to drinking was excluded because of normal values for the gamma-glutamyltransferase, and verification of sobriety by self-report, significant other, and breathalyzer. A virology panel ruled out the presence of viral hepatitis. Dietary intake before the elevation in LFTs contained elements that have established association with hepatocellular changes. The routine prescription of serial LFTs in alcoholism pharmacotherapy trials may be expected to reveal clinically nonsignificant elevations that could potentially be related to exogenous factors, such as dietary composition and should not be reflexively attributed to medication under investigation and/or drinking.

PMID: 7847604 [PubMed - indexed for MEDLINE]
Effects of long-term treatment with naltrexone on hepatic enzyme activity.




The influence of naltrexone on liver function in heroin addicts was studied, with respect to the metabolizing function by using the antipyrine clearance and to cellular damage by monitoring plasma levels of hepatic enzymes. The clearance of antipyrine was not affected by naltrexone treatment, and, during the study period, the use and withdrawal of benzodiazepines and alcohol did not change this parameter; moreover, there was no relationship between changes in plasma hepatic enzymes and antipyrine half-life. Mean plasma levels of hepatic enzymes did not show significant modification in the course of treatment with naltrexone.

PMID: 1686854 [PubMed - indexed for MEDLINE]

Effects of acute administration of naltrexone on cardiovascular function, body temperature, body weight and serum concentrations of liver enzymes in autistic children.




The effects of acute, orally administered naltrexone (0.5, 1.0, 1.5 and 2.0 mg/kg), a potent opiate receptor antagonist, on auscultated heart rate, systolic blood pressure and axillary body temperature were investigated before and about 1 h postdrug in 5 autistic children (4-12 years of age). In addition, an electrocardiogram was recorded on each child before and about 3 h after placebo or 2.0 mg/kg of naltrexone. Finally, the serum concentrations of the liver enzymes glutamic-oxaloacetic transaminase (SGOT) and glutamic-pyruvic transaminase (SGPT) were measured 24 h following placebo or naltrexone administration. Naltrexone had no statistically significant effects on any of these measures in comparison with baseline or placebo levels. Thus, these data provide preliminary evidence for the safety of acute administration of naltrexone in children.

PMID: 2721334 [PubMed - indexed for MEDLINE]

Naltrexone hydrochloride (Trexan): a review of serum transaminase elevations at high dosage.




In summary, evidence is presented associating typically asymptomatic and reversible elevations of serum transaminase values with high daily dosages of naltrexone. Statistical significance was found only between placebo and the 300 mg dosage. Subjects aged 40 years and over were significantly more likely to develop this finding than younger subjects. All subjects with significant elevations of transaminase values in these studies took daily naltrexone dosages higher than recommended for opioid addiction. The daily dosage of naltrexone recommended for opioid addiction did not cause abnormalities of serum transaminase values in these studies.

PMID: 3092099 [PubMed - indexed for MEDLINE]

Opioid receptor blockade improves mesenteric responsiveness in biliary cirrhosis.




The maximum pressure response to phenylephrine was decreased significantly in cirrhosis while chronic naltrexone treatment completely improved it (P <>

PMID: 18465246 [PubMed - indexed for MEDLINE]


[Antipruritic therapy with the oral opioid receptor antagonist naltrexone. Open, non-placebo controlled administration in 133 patients]




CONCLUSIONS: The oral opiate antagonists may well be an effective, well-tolerated therapy for intractable pruritus in many diseases.

PMID: 15517116 [PubMed - indexed for MEDLINE]
Endogenous opioids modulate hepatocyte apoptosis in a rat model of chronic cholestasis: the role of oxidative stress.




CONCLUSION: Our findings demonstrate that the administration of opioid antagonist is protective against hepatic damage in a rat model of chronic cholestasis. We suggest that increased levels of endogenous opioids contribute to hepatocytes apoptosis in cholestasis, possibly through downregulation of liver anti-oxidant defense.

PMID: 17403194 [PubMed - indexed for MEDLINE]

Involvement of endogenous opioid peptides and nitric oxide in the blunted chronotropic and inotropic responses to beta-adrenergic stimulation in cirrhotic rats.


Concurrent administration of naltrexone and L-NAME also restored to normal the basal abnormalities and the blunted responses to isoproterenol in cirrhotic rats, and did not show any antagonistic effect. Based on these findings, both the endogenous opioid peptides and NO may be involved in the attenuated chronotropic and inotropic responses to beta-adrenergic stimulation in cirrhosis. It seems that the iNOS activity results in NO-induced hyporesponsiveness to beta-adrenergic stimulation in cirrhosis.

PMID: 16968416 [PubMed - indexed for MEDLINE]

Low Dose Naltrexone January 2010 Lab Results for Hepatitis C

I started Low Dose Naltrexone (LDN) last March for Hepatitis C. I also test positive for Sjogren's Syndrome and Rheumatoid Arthritis (RA). These are my latest lab results.

I was a bit apprehensive as I didn't feel too well on the morning of my labwork - I had that "virusey" feeling and was also a bit stressed as they couldn't find the tests that they needed to run in the Quest Lab computer - so I sat for 45 minutes fuming. I had been feeling great except for that day (of course).

My HCV viral load crept up a bit from 18,729 in September to 34,524 - not too bad considering how I felt that day. Last January, pre-LDN, it was 1,280,000 and had dropped to 49,400 in June after being on LDN for 3 months. So I'm staying pretty stable - better than skyrocketing back up but not going down as I had hoped. For awhile, I was taking the 3 mg. LDN every other night, but for the last month or so, I went back to every night dosing. I will discuss with my doctor about possibly increasing the LDN dosage.

My ALT/AST were back to normal range though they weren't that high last time. In January last year, my ALT was 174, in May it dropped to 23, in Sept. it was 36 (range 6-40) and now is 34. My AST was 99 in January, 30 in May, 37 in Sept.(range 10-35) and 31 now.

Albumin (range 3.6 - 5.1) 4.8 - was 4.9 - it was 5.2 last January

Globulin (range 2.2 - 3.9) 2.9 from 3.0 - it was 3.7 last January

Bilirubin total (range 0.2 - 1.2) 0.7 from 1.1

Alkaline Phosphatase (range 33-130) 66 from 57

Total Protein - (range 6.2 - 8.3) 7.7 from 7.9 - it was 8.9 last January

Alpha Fetoprotein - 5.0 same as last time - was 6.1 which was high earlier last year.

My ferritin dropped from 80 to 38 which might be pushing it a bit - I'd been religiously taking the IP-6 along with a product called Chelaco (which my doc sells). My total iron is 136 (range 40-160) down from 165 and iron binding capacity is 373 from 352 (range 250-450)

Sjogren's level - 3.3 from 3.5 - it was 4.5 in January, pre-LDN

RA - 21 from 24 - it was 31 in January - pre-LDN

Vitamin D (range 20-100) - 59 from 49 but had been 62

Most of my other blood counts are the same - I need to talk to my doc before I try and interpret them - nothing really out of range but some of the ones that we were trying to change, via the methyl B vitamins are the same as they were in 2007. (MCV, MCH) red blood cell count, etc. I might talk to her about being tested for IF - Intrinsic Factor which can inhibit your body from absorbing B-12.

My red blood cell counts have always been on the low end - which was another argument on my part whenever a doc would try and push HCV treatment on me - ("how long before I'd be on Procrit? I'd ask them)

Slight decrease in platelets (range 140-400) 163 from 172 (186 last January)

Slight drop in red blood cell count (range 3.80-5.10) 3.84 from 3.95 (4.21 last January but 3.78 prior to that)

White blood cell count (range 3.8-10.8) 6.1 from 4.6 (6.0 from last Jan.)

Neutrophils - (range 1500-7800) 4111 from 2585 (3750 last jan.)

Eosinophils (range 15-500) 140 from 120 (102 last jan.)

Basophils (range 0-200) 24 from 14 (12 last Jan)

The LDN isn't really affecting my lymphocytes overall - some are better, some are worse.

CD3 (Mature T cells) (range - 57-85) 80 from 77

Absolute CD3+ Cells (range 840-3060) 1122 from 1008

%CD4 (Helper Cells) (range 30-61) 58 from 52

Absolute CD4+ cells (range 490-1740) 817 from 720

%CD8 (Suppressor T Cells) (range 12-42) 19 from 24

Absolute CD8+ cells (range 180-1170) 269 from 333

Helper/Suppressor ratio (range 0.86-5.00) 3.05 from 2.17

%CD16+CD56 (Natural Killer Cells) (range 4-25) 7 from 10

Absolute NK Cells (CD16+CD56 Cells) (range 70-760) 99 from 128

%CD19 (B cells) (range 6-29) 10 from 11

Absolute CD19+ Cells) (range 110-660) 139 from 134

Absolute Lymphocytes (range 850-3900) 1404 from 1308

Absolute CD3+ cells (range 840-3060) 1122 from 1008

Absolute CD4+ cells (range 490-1740) 817 from 720

Absolute CD8+ cells (range 180-1170) 269 from 333

Absolute NK Cells (CD16+CD56+ cells) (range 70-760) - 99 from 128

Absolute CD19+ cells - (range 110-660) 139 from 134

My doc also tests all of my adrenals (4 thyroid tests, progesterone, testosterone, etc.) Immunoglobulins, HHV 1-6 viruses, along with the standard CBC's, etc. All are pretty much the same as they were 2 years ago.

Overall, I'm pretty happy with the results especially as my viral load did not really increase as I had feared it might - and my LFT's have stabilized.

Dr. Berkson's 2009 Videos - Pancreatic Cancer, RA, Lupus, Lymphoma, more

Dr. Berkson was the keynote speaker at the recent Low Dose Naltrexone Conference held in Bethesda Md. at the NIH - National Institute of Health. There, he presented a 2 hour presentation detailing his successful treatments of various disorders, including pancreatic cancer, b-cell lymphoma, RA, Lupus, breast cancer, liver cancer and cirrhosis, among other diseases.

Newly published abstract about Dr. Berkon's use of ALA and LDN in treating 3 pancreatic cancer patients:


Revisiting the ALA/N (alpha-lipoic acid/low-dose naltrexone) protocol for people with metastatic and nonmetastatic pancreatic cancer: a report of 3 new cases.

Berkson BM, Rubin DM, Berkson AJ.




The Integrative Medical Center of New Mexico, Las Cruces, NM, USA.

The authors, in a previous article, described the long-term survival of a man with pancreatic cancer and metastases to the liver, treated with intravenous alpha-lipoic acid and oral low-dose naltrexone (ALA/N) without any adverse effects. He is alive and well 78 months after initial presentation. Three additional pancreatic cancer case studies are presented in this article. At the time of this writing, the first patient, GB, is alive and well 39 months after presenting with adenocarcinoma of the pancreas with metastases to the liver. The second patient, JK, who presented to the clinic with the same diagnosis was treated with the ALA/N protocol and after 5 months of therapy, PET scan demonstrated no evidence of disease. The third patient, RC, in addition to his pancreatic cancer with liver and retroperitoneal metastases, has a history of B-cell lymphoma and prostate adenocarcinoma. After 4 months of the ALA/N protocol his PET scan demonstrated no signs of cancer. In this article, the authors discuss the poly activity of ALA: as an agent that reduces oxidative stress, its ability to stabilize NF(k)B, its ability to stimulate pro-oxidant apoptosic activity, and its discriminative ability to discourage the proliferation of malignant cells. In addition, the ability of lowdose naltrexone to modulate an endogenous immune response is discussed. This is the second article published on the ALA/N protocol and the authors believe the protocol warrants clinical trial.

PMID: 20042414 [PubMed - in process]


UPDATE - May 2013 - OGF info in Pancreatic Cancer -
Newer info show that LDN itself might not be effective with PC as reported -

An explanation from Jayne Crocker -

For pancreatic cancer it is a methylation problem. I know there are some physicians who believe one way of getting around this is to give LDN to patients at night (to build up the OGF receptors) and then inject them with OGF in the day. Whether this is any more effective for pancreatic cancer than just taking OGF directly remains to be seen.


Everyone who has a chronic disease has HPA axis issues, so we are all likely to have reduced receptors. The HPA axis is skewed by the chronic sickness syndrome, which results in a weakened immune response (<10 a="" advanced="" ago="" all="" also="" amp="" and="" but="" cancer="" carcinoma="" cell="" characteristic="" chronic="" defect="" degrades="" discovered="" dr="" endorphin="" f="" has="" head="" i="" important="" in="" is="" it="" know="" loss="" mclaughlin="" nbsp="" neck="" normal="" not="" number="" of="" ogf="" posted="" rather="" receptor.="" receptor="" receptors="" remember="" s="" sickness="" specifically="" squamous="" stages="" study="" that="" the="" too="" we="" while="" work="" you="">
This is why LDN is so important in the sense that it builds up the receptors which is what increases the production of endorphins really. There are many cells in the body that produce endorphins, even T cells produce endorphins heavily during an inflammation. So if LDN drives up the OGF receptors, then it reverses one of the HPA axis problems when skewed. Adrenal Fatigue is one possible symptom when the HPA axis gets skewed.

If you are in a position to consider taking OGF directly (rather than count on LDN’s rebound effect to gain from this), I would strongly recommend trying this. Unfortunately it costs about $1,000/month so I’m not sure if this is a possibility.


OGF is Opioid Growth Factor which is the good endorphin that we all count on to benefit from taking LDN. However if there is no OGF receptor present, LDN will not be an effective treatment. If you bypass LDN, and go straight to taking OGF, this may help.

The reason LDN struggles with being effective for those with pancreatic cancer, is because the pancreas when diagnosed with cancer is unable to metabolize LDN. The problem is, when the body tries to make OGF in the pancreas, it can’t. When taking OGF directly, this works because your body doesn’t need to make it, ie metabolize it, it’s already a finished product. This effect is not possible by just taking LDN. So by taking OGF you are bypassing the problem. Please see the below email from Dr Zagon:

About 20 years ago we did an experiment with LDN and OGF as to pancreatic cancer. Amazingly to us, LDN had no effect and OGF was terrific. This was the first time we had ever seen that LDN did not work.

Well, it turns out later that while investigating pancreatic cancer, a number of researchers (not us) found that the body has a methylation of OGF precursors - called preproenkephalin. Methylation of preproenkephalin does not allow the full division of the larger preproenkephalin molecule into smaller peptides such as met-enkephalin (OGF). The bottom line is that pancreatic cancer cells do not have access to making OGF. So, if LDN works by increasing OGF (and its receptor OGFr) which can come together when LDN is no longer present - and this would normally have a super reaction by inhibiting cell proliferation, then in pancreatic cancer LDN is not going to work. It cannot upregulate - increase- OGF. As OGF is not present.

Should you wish to learn more about OGF, check out the LDNScience website http://www.ldnscience.org/opioid-growth-factor-ogf/how-does-ogf-work

But note the word methylation - perhaps Dr. Berkson's success with PC was due to the use of IV Lipoic Acid, along with other supplements - his protocol does increase methylation.

PubMed abstract on OGF and PC:

Opioid growth factor improves clinical benefit and survival in patients with advanced pancreatic cancer.

Smith JP, Bingaman SI, Mauger DT, Harvey HH, Demers LM, Zagon IS.

Department of Medicine, Pennsylvania State University, College of Medicine, Hershey Medical Center, Hershey, PA, USA.

BACKGROUND:

Advanced pancreatic cancer carries the poorest prognosis of all gastrointestinal malignancies. Once the tumor has spread beyond the margins of the pancreas, chemotherapy is the major treatment modality offered to patients; however, chemotherapy does not significantly improve survival.

OBJECTIVE:

Opioid growth factor (OGF; [Met(5)]-enkephalin) is a natural peptide that has been shown to inhibit growth of pancreatic cancer in cell culture and in nude mice. The purpose of this study was to evaluate the effects of OGF biotherapy on subjects with advanced pancreatic cancer who failed chemotherapy.

METHODS:

In a prospective phase II open-labeled clinical trial, 24 subjects who failed standard chemotherapy for advanced pancreatic cancer were treated weekly with OGF 250 µg/kg intravenously. Outcomes measured included clinical benefit, tumor response by radiographic imaging, quality of life, and survival.

RESULTS:

Clinical benefit response was experienced by 53% of OGF-treated patients compared to historical controls of 23.8% and 4.8% for gemcitabine and 5-fluorouracil (5-FU), respectively. Of the subjects surviving more than eight weeks, 62% showed either a decrease or stabilization in tumor size by computed tomography. The median survival time for OGF-treated patients was three times that of untreated patients (65.5 versus 21 days, p < 0.001). No adverse effects on hematologic or chemistry parameters were noted, and quality of life surveys suggested improvement with OGF.

LIMITATIONS:

Measurements other than survival were not allowed in control patients, and clinical benefit comparisons were made to historical controls.

CONCLUSION:

OGF biotherapy improves the clinical benefit and prolongs survival in patients with pancreatic cancer by stabilizing disease or slowing progression. The effects of OGF did not adversely alter patient quality of life. The use of OGF biotherapy at earlier stages of disease or in combination with other chemotherapeutic agents may further improve the outcome of this malignancy.

PMCID: PMC2947031 Free PMC Article

PMID: 20890374 [PubMed]

 

Even though I have provided these links in an older post, "Dr. Berkson & LDN" , these videos have just been made available and contain crucial information that might save countless numbers of people. His successful treatment of a patient with pancreatic cancer will be published in December, along with 2 other cases.
Introductory remarks - ALA - Hepatitis C

1) http://www.youtube.com/watch?v=WHyUfHqR4PA


Pet Scans - Treatment Protocol - ALA Explanation - Pancreatic Cancer with Mets to Liver (case to be published in December)

2) http://www.youtube.com/watch?v=xy65UGsVMac

Pancreatic Cancer with Mets to Liver - Hepatitis C with Liver Cancer -

3) http://www.youtube.com/watch?v=dRf8Xuqhb5Q

RA with Lymphoma from Humira - B Cell Lymphoma - Breast Cancer - Rheumatoid Disorders - Dermatomyositis -

4) http://www.youtube.com/watch?v=RXz3VIuyHHk

RA - SLE (Lupus) -

5) http://www.youtube.com/watch?v=nttilGKpJvU


ALA and purity; Asian products vs European - ALA discussion - Epstein-Barr Virus -

6) Dr Berkson Q & A Part One

http://www.youtube.com/watch?v=RsBN78Cl1s4
Lab Tests - Dosing of LDN and ALA - R Form Lipoic Acid - B Complex -

7) Dr Berkson Q & A Part Two:


http://www.youtube.com/watch?v=c29DAE4MGmo

Pancreatic Cancer & Thoughts on Treatment - ALA Gene Expression - Misc.

8) Dr. Berkson Q & A Part Three:

http://www.youtube.com/watch?v=nYxzDuKAdfI

http://www.drberkson.com/

Low Dose Naltrexone for Hepatitis C Lab Results

I had new labs done last month and they were even better than the first ones! My viral load dropped down to 18,700! In January, it was over a million - it had dropped down to 49,000 in May and keeps dropping! How low can it go? I hope to 0!!!!!

I feel pretty good now too. Much more energy. The Low Dose Naltrexone is really doing a number on my Hepatitis C virus. I had started at 3 mg. a night but now take it every other night and it still seems to be working......for me, it seems that less is more with the LDN.

I belong to a Yahoo support group called:

Hepatitis Children and CAM Alternatives

Click to join Hepatitis_Children_and_CAM_Alternatives

Despite it's name, there are a great many adults who have various forms of Hepatitis. C, B or autoimmune. Many of the members are also using LDN for their conditions and all are having great results.

If you are considering using the combo treatment of interferon and ribavirin to treat your Hepatitis C, or have tried it and failed treatment or had to stop because of the side effects, please consider using Low Dose Naltrexone instead. Other than initial sleep disturbances, there are very few, if any, side effects. It is very inexpensive as well. My 3 month supply costs about $50.00 and I get it from Skip's Pharmacy through the mail. Their site is here:


Skip's Pharmacy

On another note, my fibromyalgia, IBD, and chemical sensitivities are much, much better as well. The combination of a gluten/dairy free diet and the LDN has made all the difference in the world.

Not Ready For Any Support Group

For many years, I have sought alternative or natural solutions to treat my Hepatitis C virus and have basically learned to "take charge of my health". and to question my doctors and whatever pharmaceuticals that they prescribe (or try to prescribe) to me.

I have refused the current interferon/ribavirin "treatment" for Hep-C for many reasons. The main reason is that it doesn't really work, particularly on my genotype (kind of strain) of 1b, and it is horrendously toxic and damaging to the immune system. I was fortunate that my biopsy done in 2003 showed only minor inflammation at Stage 1/Grade 1 and the virus has not really progressed - thankfully.

My initial information about hep-c (and most other disorders) came from the wonderful book, "Prescription for Nutritional Healing" - which I credit for saving my life. I had seen the book at Whole Foods Market sometime in the 90's and bought one at a garage sale around 1997-98. I learned about Milk Thistle and began taking it as I thought that it might provide my liver some kind of protection against my drinking - I had pretty much quit doing any kind of hard drugs by then, but I still loved my beer. At any rate, I found out that I had the virus in 2002 and my 2003 biopsy revealed (amazingly enough) little damage. What was also extremely amazing to me was that my liver was still functioning at all as I had several decades of extensive drug/alcohol use/abuse as well. And I mean serious, hard drugs too. I can only surmise that the milk thistle might have protected and repaired my liver enough to prevent anything worse.. But who knows? Matthew Dolan's great book, The Hepatitis Handbook is another great souce - I hope that he updates it someday.

I'm doing great with my own research and with the help of my great doctor, Dr. Kashi Rai. I will attempt to chronicle my battle with the Hep-C dragon, as well as my 7 herpes viruses, (HHV-1, HHV-2, Herpes Zoster, EBV (epstein barr), CMV, and the newly emerged HHV-6) as well as my gluten, dairy, nut, most seafood food intolerance. My favorite book about Celiac/Gluten intolerance is Dangerous Grains by James Braly and Ron Hoggan.

I share my life with 10 cats, now 9 since Brooks died in October.. ( of which 8 of them and I lived through the flood after the levee breaches following Hurricane Katrina) while I continue with the daily juggling act of surviving in post-Katrina New Orleans. Brooks had been battling end stage renal failure and I did the best that I could to help make his last bit of time, good time.

New Orleans is still recovering from Hurricane Katrina, or more accurately, the flooding caused by the breaches in the levees and floodwalls that were constructed by the Federal Government's U.S. Army Corps of Engineers. To learn why New Orleans flooded - and it was not due to a "natural disaster" but due to the "Worst Engineering Disaster in History" as cited by The American Society of Civil Engineers, check out Levees.org

I should know. My car broke down 2 days before Katrina - which was up until that Friday, still supposed to hit the panhandle of Florida. I had 8 cats and took care of dozens of feral cats in my neighborhood. I was broke and I refused to leave the cats behind.

The storm on Monday, August 29th, 2005, was pretty scary but afterwards, I was able to use my cell phone to call up friends to let them know that everything was ok. There were trees down and wind damage but really, not much rain at all. Then, the water started gradually coming up - and kept rising. Soon, I could hear dogs up and down the block barking and yelping until I didn't hear them anymore. My feral porch cat, Emerald, had ridden out the storm underneath the house, as did most of the feral cats in New Orleans - a city of raised homes. I heard her crying and I tried to get to her through the floor furnace - but when I got it opened , water gushed in........and I never heard or saw Emerald again.

The rest of the day and night are a blur to me now - my mind fractured off into the surreal - like watching a movie of someone else. I managed to climb up into a 7 foot high closet before passing out from shock, exhaustion and hyperthermia. But I woke several times during that long night and could hear my cats crying in terror.

The next morning, I woke and could hear what sounded like copters flying overhead. But all that I wanted to do was to lie there and never move again. One of the cats started crying pitifully from the front room and I opened my eyes to see her clinging to the curtains. This got me moving and out of the closet and down into the water that came up to my neck.

During the next hour, I was able to break out my back windows and swim 3 of the cats out to the carport roof - I could only find 2 carriers as they had sunk down somewhere on the floor in the murky water. The 5 others were placed up into the same closet that had given me refuge and another feral cat swam outside to cling onto the limbs of a tree.

I was rescued by a first responder in an airboat and taken to the railroad tracks nearby. Soon, the Missouri Coast Guard picked me and the 3 cats up and took us out to the Interstate. Eventually, a school bus took us, and other rescued folks and their pets to a shelter in Thibodaux, La. - about 40 miles west of New Orleans. I spent several days there in pretty primative conditions - no electricity, no phones, no email.

Family members were finally contacted and they came to get me 5 days later. It took another 2 days to get to where my Mom had evacuated to - in Birmingham, Alabama, where we had relatives. But throughout this ordeal, I was obsessed about the poor cats that I left up in that closet and I contacted every rescue group listed to try and get someone, anyone to go save them.

Finally, after getting no responses, I decided to go back to New Orleans to get them myself. Everyone told me that it would be impossible - the city was under lock down and no one was being allowed back in. Huh. Through an internet chat room, I met a man named Steve Vicknair who was in Houston, Texas. He had a boat and he wanted to help people like me rescue their pets.

And that is what we did. On September 11th, 2005 - two weeks! after Katrina, we got back to my still flooded apartment to find all cats still alive!!!! They had no food or water for all of that time - but they survived!!!!!

I stayed in Birmingham with my Mom (and the 8 cats) for 6 months until her health declined and she moved into an Assisted Living facility. Her house (and my inheritance) had taken in 11 feet of water and was very underinsured. She did have flood insurance as did most of the families in New Orleans - but the very minimum. We fought with Traveler's home owner's insurance for almost 2 years before they paid my Mom what she was owed. But the house could not be repaired.

I moved back to New Orleans in March of 2006 into an apartment in the Mid-City area - an area that had not gotten too much flooding compared to the 80% of the rest of the city. I got back involved with animal rescue, cats in particular...it was still a hairy time, with packs of dogs running wild in the streets and many, many starving animals. Things have somewhat improved but the animals of New Orleans still need so much help.

ARNO - Animal Rescue New Orleans - is still here. It is an all volunteer group that was formed shortly after Katrina - and has probably done the most out of all of the rescue groups:

The Katrina pictures that I managed to take when the water came up......and months later:

Katrina

The Cat Rescue pics:

Cat Rescue

Mom's House

My health gradually deteriorated in those first years back - my health care had been provided at Charity Hospital for about 3 years before Katrina, but it had to close - and is still closed. However their clinics still remained open - an emergency one had been set up at the Lord & Taylor department store near the devastated Superdome - that was so strange to go there for medical treatment, when a year earlier I had shopped for shoes.....

I developed shingles, and a strong chemical sensitivity - possibly due to the stress and perhaps being in the water during and after Katrina. I was in constant pain from fibromyalgia and my IBD often prevented me from leaving the house.

Thankfully, I was able to get Social Security disability - 3 years in the making - it only provides $693.00 a month but I do get Medicare, which enabled me to find Dr. Rai - the doctor who led me to Dr. Berkson - who changed my life.

I could never live anywhere else - New Orleans is and forever will be - the center of the universe!