Anti cancer turmeric may cause toxicity - severe liver injury and formation of kidney stones

[ginfreely]

 

[ginfreely]

 

[ginfreely]

 

[ginfreely]

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Hepatotoxicity​

Both turmeric and curcumin were considered to be generally safe and for many years had not been linked to instances of liver injury in any consistent way. Studies of its use in various diseases showed low rates of transient and asymptomatic serum enzyme elevations during therapy, but without instances of clinically apparent acute liver injury. Indeed, turmeric was evaluated as a potential therapy of acute and chronic liver injury and although its efficacy and safety were not clearly shown, therapy with turmeric and curcumin did not seem to worsen the preexisting liver conditions. Recently, isolated case reports of liver injury arising during use of turmeric dietary supplements have been published. Initially, these episodes were attributed to other exposures that might have accounted for the injury or possible contaminants in the commercial turmeric products. One reason given for the safety and lack of hepatotoxicity of curcumin was that it is poorly absorbed by the oral route, and it was unclear whether there was adequate systemic exposure to achieve any of the purported beneficial or adverse effects of turmeric or curcumin.

Importantly, means of increasing the bioavailability of curcumin were developed using piperine (black pepper) or nanoparticle delivery methods to increase absorption. These high bioavailability forms of purified curcumin were subsequently linked to several cases of liver injury and mentioned as a possible cause of outbreaks of acute hepatitis with jaundice in Italy. The clinical features of the liver injury attributed to high bioavailable forms of curcumin have recently become better defined. The latency to onset of liver injury has varied from a few weeks to as long as eight months but is typically 1 to 4 months. The onset is insidious with fatigue, nausea and poor appetite followed by dark urine and jaundice. Rash and fever are absent or mild. Laboratory tests at onset typically show marked elevations in serum aminotransferase levels (often above 1000 U/L) with only mild increases in alkaline phosphatase. Jaundice occurs if the agent is continued. While signs of hypersensitivity are not prominent, many patients develop autoantibodies and the clinical syndrome and histological features can resemble autoimmune hepatitis. Prednisone has been used to treat severe cases of turmeric hepatotoxicity but is probably not needed as recovery is rapid once the herbal product is discontinued. While reports of acute liver failure has been attributed to turmeric, most cases resolve completely without evidence of chronic injury or bile duct loss. The hepatocellular pattern of injury and frequency of jaundice suggest that fatal instances might occur at a rate of 10% of jaundiced cases, particularly if the product is not discontinued promptly.

Likelihood score: B (likely cause of clinically apparent liver injury).

https://www.ncbi.nlm.nih.gov/books/NBK548561/

 

[ginfreely]

Mechanism of Injury​

The acute hepatotoxicity caused by turmeric appears to be due to an idiosyncratic injury, perhaps immunologically mediated. The association with HLA-B*35:01 suggests that the injury is linked to the immune system and perhaps interaction with curcumin or another component of turmeric with the HLA molecule leading to T cell recognition of a self-antigen on liver cells and immune mediated injury. The HLA-B* 35:01 allele is also linked to liver injury due to green tea (Camellia sinensis), Garcinia cambogia, and Polygonum multiflorum (also known as Fo-ti). These 4 herbs all have bioactive constituents that are polyphenols.

 

[ginfreely]

Outcome and Management​

Most cases of acute hepatic injury from turmeric resolve within 1 to 3 months of stopping the medication. In some instances, however, the injury is severe and unremitting, leading to acute liver failure and either death or need for liver transplantation. A severe outcome is more likely if turmeric is continued after the appearance of symptoms and signs of liver injury. There appears to be no cross sensitivity to hepatic injury between turmeric and other herbal products. However, reexposure to turmeric should be avoided as recurrence and more severe liver injury can occur with rechallenge.

 

[ginfreely]

CASE REPORTS​

Case 1. Acute hepatitis with jaundice attributed to turmeric. Case 3.(1)​

A 57 year old woman with recurrent urinary tract infections, migraine headaches, and osteoarthritis developed fatigue, nausea, abdominal pain, and anorexia, followed by itching, dark urine, and jaundice. Because of a recurrence of cystitis, she had received a 7-day course of nitrofurantoin 4 months previously and a 7-day course of cephalexin a few weeks previously. Because of persistence of symptoms, she started an over-the-counter preparation of turmeric (Nature’s Way Turmeric, 500 mg once daily) 2 to 3 weeks before onset of symptoms. She had no history of liver disease, did not drink alcohol, and had no risk factors for viral hepatitis. Her other medications included rizatriptan, salbutamol, vitamin C and D, and a multivitamin. On presentation, her serum bilirubin was 9.1 mg/dL, ALT 1425 U/L, AST 1374 U/L, and alkaline phosphatase 250 U/L and she was admitted to a hospital for evaluation. The INR was 1.3 and albumin 3.7 g/dL. Tests for hepatitis A, B, and C were negative. The ANA was positive (1:640), but SMA and AMA were negative and IgG levels were normal (1170 mg/dL). Abdominal ultrasound showed a right renal stone without hydronephrosis and normal appearing liver without evidence of biliary obstruction or gallstones. A liver biopsy showed acute inflammation and necrosis with eosinophils; plasma cells were not prominent and there was no fibrosis. Turmeric had been stopped and her liver tests improved rapidly without specific therapy (see Table). Serum bilirubin levels fell into the normal range within 6 weeks and aminotransferase levels within 3 months of stopping turmeric. When seen in follow up a year after onset, she was asymptomatic, and all liver tests were normal.

Key Points​

Medication:	Turmeric (500 mg once daily)
Pattern:	Mixed (R=13.7)
Severity:	3+ (jaundice, hospitalization)
Latency:	3 weeks
Recovery:	Complete within 2 months
Other medications:	Rizatriptan, salbutamol, vitamins

Laboratory Values​

Time After Starting	Time After Stopping	ALT (U/L)	Alk P (U/L)	Bilirubin (mg/dL)	Other
0		Started Turmeric (500 mg daily)
3 weeks	-1 week	Developed symptoms of fatigue, nausea
4 weeks	0	Stopped turmeric
5 weeks	7 days	1425	250	9.1	Admitted
	9 days	1145	306	11.5	Liver biopsy
6 weeks	14 days	747	268	8.1	Discharged
7 weeks	21 days	466	292	4.8
9 weeks	34 days	95	183	2.5
	48 days	40	170	1.4
	3 months	34	136	1.1
	1 year	18	104	0.7
Upper Limit of Normal	50	125	1.2

Comment​

A middle aged woman developed acute, icteric hepatitis 2 to 3 weeks after starting turmeric for recurrent urinary tract infections that had not responded to nitrofurantoin or cephalosporins. The liver injury began to improve within 1-2 weeks of stopping the turmeric and without other specific therapy. The turmeric product tested positive for curcumin and was negative for other potentially toxic herbal products as well as black pepper. The patient was homozygous for HLA-B*35:01, an HLA allele closely linked to liver injury from several herbal products including turmeric, green tea, Fo-ti, and garcinia. The clinical features of female sex, hepatocellular liver injury, low levels of autoantibodies, lack of rash and fever, and rapid improvement on stopping the product are typical of turmeric induced liver injury. While she had also been exposed to nitrofurantoin and cephalexin, the latency to onset was not compatible with those two antibiotics and cephalexin is a very rare cause of liver injury which is typically cholestatic.

 

[ginfreely]

Case 3. Fatal case of acute liver injury attributed to turmeric. Case 10.(1)​

A 62 year old woman developed fatigue and nausea followed by dark urine and jaundice having taken a turmeric root extract (Rite Aid: Turmeric, 500 mg) once daily for wellbeing and arthritis for the previous 14 months. She had no history of liver disease, excessive alcohol intake, or risk factors for viral hepatitis. Her medical conditions included osteoarthritis, season allergies, menopausal symptoms, and uterine fibroids. Her medications included estrogens, pseudoephedrine, diphenhydramine, salbutamol, tramadol, magnesium, fish oil, ginger, glucosamine, vitamins C and D, and a multivitamin, all of which she had taken for more than a year. She stopped the turmeric and 3 days later was seen and found to have abnormal liver tests (bilirubin 2.5 mg/dL, ALT 1230 U/L, AST 1628 U/L, alkaline phosphatase 329 U/L). She was admitted to the hospital briefly. Tests for hepatitis A, B, C and E and for CMV and HSV infection were negative as were routine autoantibody and serum IgG levels. She was discharged and followed as an outpatient, but her condition worsened with bilirubin rising to 13.5 mg/dL and INR to 2.0. She was readmitted. Imaging of the liver showed evidence of diffuse hepatocellular disease, a nodular liver, and ascites. She was listed for emergency liver transplantation but suffered an acute myocardial infarction and ultimately developed multiorgan failure and died one month after initial presentation. An autopsy showed a shrunken liver, massive hepatic necrosis, a ruptured posterior leaflet of the mitral value, and recent myocardial infarction.

Key Points​

Medication:	Turmeric 500 mg daily
Pattern:	Hepatocellular (R=14)
Severity:	5+ (death within six months of onset from acute liver failure)
Latency:	14 months
Recovery:	None
Other medications:	Estrogens, pseudoephedrine, diphenhydramine, salbutamol, tramadol, fish oil, magnesium, glucosamine, ginger, vitamins

Laboratory Values​

Time After Starting	Time After Stopping	ALT (U/L)	Alk P (U/L)	Bilirubin (mg/dL)	INR	Other
0		Started Turmeric (500 mg daily)
14 months	0	Curcumin stopped, symptoms of fatigue and jaundice
	3 days	1230	329	2.5		Admitted
	7 days	1360	333	6.1		Methylprednisolone, 6 days
	10 days	1277	311	8.6	1.5	Discharged
	13 days	1088	251	13.5	2.0
	17 days	898	329	17.5	1.4	Readmission
	19 days	704	303	18.7	2.3
15 months	20 days	513	249	16.8	2.1	Acute myocardial infarction
	22 days	530	280	23.6	2.3
	26 days	171	160	22.8	2.5	Listed for liver transplantation
	33 days					Died of multiorgan failure
Upper Limit of Normal	35	135	1.2

Comment​

A 62 year old woman developed a severe acute hepatitis 14 months after starting turmeric. No other cause for the liver injury was identified. The liver injury did not improve with stopping turmeric and within 3 weeks she demonstrated evidence of acute liver failure. She was listed for liver transplantation but developed an acute myocardial infarction and rapidly developed multiorgan failure and died within 5 weeks of onset. Chemical analysis was done on the herbal product which demonstrated the presence of turmeric without black pepper or other potentially hepatotoxins or herbs. The patient was negative for HLA-B*35:01. The case was judged to be only “probable” liver injury due to turmeric. Against the diagnosis was the long latency (greater than a year), lack of improvement with stopping the herbal product, and absence of HLA-B*35:01.

 

[eatshitndie]

especially from india where they add artificial coloring to turn it bright orange and reddish.

 

[Balls2U]

Someone gave me a packet of tumeric powder in 2022. I didn't open it until recently. The powder is black in colour. Does it mean that the powder had turned black or is black the original colour?

 

[eatshitndie]

Someone gave me a packet of tumeric powder in 2022. I didn't open it until recently. The powder is black in colour. Does it mean that the powder had turned black or is black the original colour?

original color should be orange yellow, although some virginal color may be bright yellow. if it’s black it has oxidized and probably gone bad.

 

[ginfreely]

original color should be orange yellow, although some virginal color may be bright yellow. if it’s black it has oxidized and probably gone bad.
View attachment 209287

Fo from my cancer threads your mother virginal color is then yellow Pui!

 

[ginfreely]

Someone gave me a packet of tumeric powder in 2022. I didn't open it until recently. The powder is black in colour. Does it mean that the powder had turned black or is black the original colour?

You too evil shameless Cantonese dog son of prostitute so evil so cheap lowlife take benefits from my cancer threads and insult me hokkien virgin as chicken non stop 无赖地痞流氓广东狗呸！

 

[Balls2U]

You too evil shameless Cantonese dog son of prostitute so evil so cheap lowlife take benefits from my cancer threads and insult me hokkien virgin as chicken non stop 无赖地痞流氓广东狗呸！

What benefits are you talking about, you delulu slut? The positive effects of tumeric on cancer treatment is common knowledge and widely available long before your hymen was broken.

 

[ginfreely]

What benefits are you talking about, you delulu slut? The positive effects of tumeric on cancer treatment is common knowledge and widely available long before your hymen was broken.

You evil ingrate serial liar Cantonese dog son of prostitute no benefits you will keep reading my cancer threads? Of course not. 说谎精无赖地痞流氓广东狗呸！

 

[Balls2U]

You evil ingrate serial liar Cantonese dog son of prostitute no benefits you will keep reading my cancer threads? Of course not. 说谎精无赖地痞流氓广东狗呸！

That's because you're spamming all your trash everywhere, you delulu slut.

 

[Balls2U]

 

[ginfreely]

That's because you're spamming all your trash everywhere, you delulu slut.

Slut is you and your cheap sell nude sell cb women and shameless liar is you my cancer thread is only one a day. Take benefits and do evil to your benefactor and tell lies deny got benefits 真够贱. Pui!

 

[ginfreely]

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