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Overlooked & Overworked

March 2000

By Karin Granstrom Jordan, MD

Fibrosis, cirrhosis and alcohol

A characteristic feature of liver disease, regardless of its cause, is the increased deposition of collagen, the connective tissue protein. This increased collagen accumulation could result from enhanced collagen biosynthesis and/or decreased collagen breakdown. PPC appears to increase collagen breakdown by stimulating collagenase activity in hepatic stellate cells preventing the development of fibrosis and cirrhosis (Li J et al., 1992). Several studies have focused on PPC and its effect on collagen and fibrosis.

A baboon study (Lieber CS et al., 1994) confirmed earlier results (Lieber CS et al., 1990) showing that in the baboon, feeding of ethanol (a form of alcohol) results in hepatic fibrosis and cirrhosis even when associated with an adequate diet. This effect could be prevented by supplementing the diet with a 94-96% pure PPC preparation. None of the eight animals fed alcohol with PPC for up to 6.5 years had progression to fibrosis or cirrhosis as had 10 of 12 unsupplemented baboons, a highly significant difference. Another study (Ma X et al., 1996) revealed that PPC reduces hepatic fibrosis induced by either carbon tetrachloride or human albumin in rats, and that PPC not only prevents the development of fibrosis but accelerates the regression of pre-existing fibrosis. The study further suggested that the protective effect exerted by PPC against fibrosis is due, at least in part to increased collagen breakdown.

One of the ways PPC helps prevent liver damage from alcohol is by inhibiting an enzyme known as CYP 2E1. Chronic alcohol consumption raises levels of this enzyme, which is involved in the metabolism of alcohol. This leads to oxidative stress and acetaldehyde production, which stresses the antioxidant defense system and depletes glutathione. CYP 2E1 also furthers the production of toxic metabolites from common drugs such as acetaminophen and promotes carcinogenesis. CYP 2E1 inhibitors protect the liver from alcohol-induced damage, but drugs tested for this purpose have been too toxic for practical use. However it has recently been discovered that PPC significantly inhibits CYP 2E1 activity (Lieber CS, 1999; Aleynik MK et al., 1999), providing a potential nontoxic solution to this problem.

Alcohol and the pancreas

The pancreas is essential to both digestion and glucose regulation. It secretes digestive enzymes into the duodenum for protein, carbohydrate and fat digestion, and produces large amounts of sodium bicarbonate (as found in baking soda) to neutralize stomach acid in the duodenum. The islets of the pancreas produce insulin and the related hormones glucagon and somatostatin.

Pancreatitis-inflammation of the pancreas-is caused primarily by overconsumption of alcohol in about 80% of cases. Ethanol causes severe oxidative stress in the pancreas, probably due to increased production of free radicals and depletion of glutathione and other antioxidants. In particular, both alcohol intake and pancreatitis are associated with rises in the CYP 2E1 enzyme in the pancreas.

The research group that investigated the correction of alcohol-induced liver damage by PPC has recently published research demonstrating the same protective effect in the pancreas (Aleynik SI, Leo MA, Aleynik MK et al., 1999). When rats were given ethanol, markers of oxidative stress in the pancreas rose sharply. However PPC given along with the ethanol prevented this rise, and almost completely alleviated the depletion of pancreatic glutathione caused by ethanol.

The protective effect of PPC on oxidative stress in the pancreas was even more pronounced than these researchers had observed in the liver of baboons fed alcohol. PPC may protect the pancreas from other causes of oxidative stress; as the authors state, PPC "could provide innocuous but effective and orally active antioxidant therapy, not only as shown before for liver injury, but also, as shown here, for early pancreatic changes."

Antioxidant effects

As we have seen, a key mechanism of PPC action is its antioxidant effect. Despite its rich content of polyunsaturated linoleic acid, PPC has been shown to effectively reduce oxidative stress caused by alcohol in the liver and pancreas, as well as in LDL cholesterol.

Newly published research (Aleynik SI, Leo MA, Takeshige U et al., 1999) identifies the constituent of PPC primarily responsible for its antioxidant effect. This constituent, DLPC, comprises 40-52% of PPC. The researchers found that the "remarkable" antioxidant effect of PPC on oxidative stress induced in hepatoma cells by arachidonic acid could be accounted for by the DLPC contained in it.

DLPC appears to be primarily responsible for many of the protective actions of PPC on the liver and pancreas. A new study demonstrates that DLPC stimulates the Kupffer cells of the liver to decrease production of the hepatotoxic tumor necrosis factor-a, while increasing production of the hepatoprotective interleukin-1b (Oneta CM et al., 1999). DLPC also appears to decrease activation of collagen-producing stellate cells in the liver, and to increase collagenase activity and thus collagen breakdown, asdiscussed above.

PPC in hepatitis

PPC has been found to decrease serum aminotransferases in experimental hepatitis. In 1998, Niederau et al. conducted a multi-center randomized, placebo-controlled clinical study evaluating the effects of PPC in combination with interferon alpha (IFN) in patients suffering from Hepatitis B and C. IFN is the standard treatment for these diseases, however only 50% of patients with Hepatitis B and 20-30% of patients with Hepatitis C respond to this antiviral drug with long-term normalization of serum aminotransferases. Among patients with hepatitis C that do respond to IFN while under treatment, there is at least a 50% relapse rate. Evidently there is a need for more effective treatment.

In this study 176 patients completed the protocol. All patients were given the same amount of interferon during the 24-week test period. In addition patients were randomly assigned to receive either 1.8 grams per day of PPC or placebo for the same 24 weeks. A biochemical response to therapy was defined as minimum 50% reduction of ALT compared to pre-treatment values.

The results show that PPC increased the response rate to IFN in chronic viral hepatitis C (71% versus 51 % in the placebo group). Prolonged PPC therapy given to responders 24 weeks beyond the cessation of interferon therapy tended to increase the rate of sustained responses in patients with hepatitis C (41% versus 15%). Hepatitis B patients, however, did not have an improved biochemical response to interferon from PPC. The reason why PPC showed beneficial effect in hepatitis C and not in hepatitis B is not clear and will be further investigated.

This study suggests that PPC can be a valuable adjunct to IFN treatment of Hepatitis C as well as be of beneficial use after cessation of IFN therapy in order to increase the chance of sustained response to therapy.

The benefits of protection

Modern living unfortunately involves daily exposure to substances that are toxic to our bodies, which can impose heavy stresses on the vital organs we have discussed. Therefore it is logical to think that all of us can benefit from some kind of support in maintaining the vitality of these organs. In particular, individuals with a substantial alcohol consumption, with obesity, diabetes or with high exposure to NSAIDs or environmental toxins have an even greater reason to take protective measures because of the documented risk of developing serious pathologies.

Knowing that conventional medicine has very little to offer in the prevention or early treatment of the disorders we have discussed, it seems wise to remember that prevention is the best cure. We are fortunate today to have access to a natural protective remedy that is safe, effective and without significant side effects.

And it is good to know that protection of the liver, pancreas and stomach is beneficial not only for these vital organs themselves, but for the overall health and vitality of our body.


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