PADMA 28 & Intermittent Claudication

Discussion in 'Fibromyalgia Main Forum' started by tansy, Jan 7, 2006.

  1. tansy

    tansy New Member

    by Guy Braveman (medical student)


    Tibetan Medicine

    Tibetan medicine is one of the oldest medicines in the world and only became open to public eyes after the Chinese occupation of Tibet in 1959, when the Dalai Lama established the Tibetan Medical Institute in Dharamsala. This medical system draws from knowledge of India (Ayurveda and Siddha), China, Persia, and Greece which means it integrates acupuncture, herbalism, massage, yoga and meditation with indigenous knowledge of healing plants and minerals, and the Buddhist understanding of the mind-body relationship.

    Practitioners aim to accomplish the six perfections - wisdom, giving, ethics, patience, concentration and effort. They believe that health is maintained by the balance of three complementary energy systems in the body, wind - responsible for activity, bile – responsible for vitality, and phlegm – responsible for stability. Imbalances in the energy systems are created by ignorance, improper diet and interaction with the environment.

    Tibetan doctors diagnose by urine analysis, tongue diagnosis, pulse taking, and extensive questioning to determine nature of illness. First the constitution is determined (as in phlegm, bile, or wind). Then the pulse is taken to determine health of each organ. Next the urine is checked for colour, vapour, taste, froth, and odour.

    Treatment aims to readjust the balance of the energies and is approached on four levels beginning with dietary changes, herbs and massage, acupuncture and moxibustion and finally the most intensive yoga and meditation.



    PADMA 28


    PADMA 28 is a potent Tibetan antioxidant, formulated 2,000 years ago, it is based on a combination of 19 herbs together with natural camphor, sorbitol, calcium sulphate and silicon dioxide.

    This formulation was carried by Tibetan Buddhists, philosophers and doctors in the 18th century, to the west, finally arriving in Switzerland in 1960s. The formulation was preserved by Mr. Karl Lutz, and is manufactured commercially today by a Swiss company PADMA AG, with each tablet containing the following ingredients.



    Allspice 25mg 11. Margosa 35mg 21. Camphor 4mg

    Bengal Quince 20mg 12. Marigold 5mg 22. Silicon Dioxide 12mg

    Cardamom 30mg 13. Myrobalan 30mg 23. Sorbitol 73mg

    Cloves 12mg 14. Potentilla Golden Herb 15mg

    Columbine 15mg 15. Red Sandalwood 30mg

    Gingerlily 10mg 16. Ribwort 15mg

    Heartleaved Sida 10mg 17. Saussuria 40mg

    Iceland Moss 40mg 18. Valerian 10mg

    KnotGrass 15mg 19. Wild Lettuce 6mg

    Licorice 15mg 20. Calcium Sulphate 20mg

    PADMA 28 & Intermittent Claudication



    Peripheral Arterial Occlusive Disease (PAOD) is usually due to atherosclerosis and causes include smoking, overweight and elevated levels of blood cholesterol and other fatty substances. Its main clinical feature is intermittent claudication, a pain in muscle, most often the calf, due to ischaemia brought on by exercise and relieved by rest. PAOD affects an estimated 12% of older adults, and that number is expected to increase as the population ages.

    Traditional Tibetan doctors recognise atherosclerosis as "a condition resulting from excess heat", and attribute it to overindulgence in meat, fats and alcohol, and PADMA 28 has been used in traditional Tibetan medicine to treat conditions caused by over-consumption of meat, fat, and alcohol.

    This formula has powerful anti-oxidant effects which has been shown in various trials to alleviate the immobility and pain of intermittent claudication.



    In 1998 the efficacy of PADMA 28 in the treatment of intermittent claudication with objective assessment of chronic occlusive arterial disease patients was investigated. Using objective, non-invasive techniques of vascular testing, a randomised, 6 month double-blind pilot study assessed the efficacy, safety and tolerance of PADMA 28 (two 403mg capsules BD) in 72 patients with intermittent claudication compared to controls. PADMA 28 patients displayed a significant mean improvement of 12% in exercise-induced drop of ankle pressure and 0.8 min in pressure recovery time compared to pre-treatment values. An improvement in pressure drops by more than 15%, compared to a deterioration or no change, occurred in 48% of PADMA 28 patients compared to 18.8% in controls.

    Self-assessment by patients revealed that perceived improvement in pain-free walking ability in the PADMA 28 group correlated significantly with improvement in exercise-induced drop of ankle pressure. PADMA 28 was well tolerated, with minimal unwanted side-effects and associated with a significant improvement in patient well-being compared to controls.
    The pilot study demonstrates that following the stress of exercise, changes in ankle systolic pressure and its recovery time are positively affected by PADMA 28. Results suggest that PADMA 28 may be an effective treatment for intermittent claudication.



    In 1995, in a double-blind study, 93 patients with intermittent claudication received PADMA 28 (760 mg BID) or a placebo for 16 weeks. The average walking distance increased by 115% in patients receiving PADMA 28, compared with a 17% increase in the placebo group (a statistically significant difference).



    In 1994 thirty-six patients with stable intermittent claudication were randomised in a double-blind study either to treatment with two tablets of PADMA 28 twice daily (containing 340mg) or placebo for four months. Effect of treatment was quantified by pain-free and maximal walking distances on a tread-mill. The actively treated group attained a significant increase in pain-free walking distance from 115 m (72-218) to 227 m (73- >1000, p < 0.05). The placebo group did not show significant changes in either pain-free or maximal walking distance. The study showed that treatment with PADMA 28 over a four month period significantly increases the walking distance in patients with stable intermittent claudication of long duration.



    In 1994 93 patients between the ages of 35 and 65 with pre-established diagnosis of intermittent claudication were randomised in a placebo-controlled, double-blind trial of 16 weeks' duration. PADMA 28 (380 mg) 2 capsules twice daily or placebo capsules were given for 16 weeks. Patients that received PADMA 28 exhibited on standardised ergometry an increase of maximum walking distance from 87.5 to 187.7 m. The patients receiving placebo showed a non-significant increase of 12.5 m. The increase in walking distance of the group receiving PADMA 28 compared with placebo was highly significant after 12 and 16 weeks. They concluded PADMA 28 shows clinically relevant effectiveness in peripheral arterial occlusive disease of the lower extremities.



    In 1991 in 100 patients took part in a double blind, randomised, study, all with diagnosed arteriosclerosis affecting the lower extremities in II stage according to Fontain. In 50 patients a preparation of PADMA 28 was applied for 16 weeks, and 50 were given placebo. A marked, statistically significant elongation of the claudication distance was achieved in the patients given PADMA 28. This was measured, under standardised condition, on an ergometer-treadmill. Moreover, there was also a decrease in the index of blood platelets aggregation, a drop in the level of cholesterol, triglycerides, total lipids, beta lipoproteins, and an increase in ++alpha lipoproteins. No positive results were observed in the placebo group. They concluded PADMA 28 may be a useful adjuvant to therapeutic methods with regard to chronic ischaemia of the lower extremities in II stage, according to Fontain.



    In 1985 a placebo-controlled double blind study showed the effect of PADMA 28 on patients with intermittent claudication. After 16 weeks the patients treated with PADMA 28 exhibited on standardised ergometry an increase of some 100% (p less than 0.01) in the maximum as well as pain free walking distance. The control patients showed increases of 21% in maximum (p less than 0.05 as compared to PADMA 28), and 46% in pain free walking distance.





    How Does It Work?



    PADMA 28 As An Anti-Atherosclerotic

    In 1994 Winther et al. did a study on 36 patients with a median duration of stable intermittent claudication of five years, who were randomised to either active treatment with PADMA 28 (340mg BD) or placebo for four months.

    Three statistically significant findings during active drug treatment were found: the "oxidative burst" of monocytes, as measured by chemiluminescence, decreased from 75.6 mVolt to 53.5 mVolt; euglobulin clot Iysis time was shortened by approximately 40%, signifying a sharp increase in fibrinolytic activity, and PAI-1 activity decreased from 14.6 to 10.1 IU/ml (p < 0.05). Patients on placebo showed no significant changes in any of these parameters.

    So they showed both the oxidative burst decreased and fibrinolysis increased.

    The oxidative burst response of monocytes has been reported to modify the oxidation of LDL-cholesterol. When LDL is oxidised it is taken up by monocytes, which are then transformed into foam cells, one of the main components of the young atherosclerotic plaque. Inhibition of the oxidative burst response, with consequent reduction of the oxidised LDL available to form foam cells, might in this way slow the development of atherosclerosis.

    Fibrinolysis serves as the natural protection against thrombus formation, so an increase in this is obviously beneficial.



    These results can be explained two ways: that they are the direct pharmacological action of some as yet unidentified component of PADMA-28, or it is simply indirect effects of the greater physical activity which the treated patients could, and presumably did, undertake.

    It is known that physical exercise such as walking and bicycling augments fibrinolysis and even moderate exercise for 10 minutes can increase t-PA activity four-fold and decrease PAI-1 activity.13

    However greater physical activity cannot really explain the decreased oxidative burst response of monocytes under PADMA-28 therapy. Having said this physical activity is known to modify the capacity of macrophages for chemotaxis, migration and phagocytosis in animal models and monocyte count and function are likewise influenced by exercise in healthy young people.



    They concluded that PADMA 28 ‘augments fibrinolysis and decreases the oxidative burst response of monocytes in patients with atherosclerosis. Whether these findings are a direct effect of PADMA on the fibrinolytic and immunologic systems, or, an indirect effect of the better walking capacity during PADMA therapy, is not clear’.



    In 1995 Matzner et al. confirmed the antioxidant effects Winther showed. Human neutrophils were studied in vitro in the presence of PADMA 28. There results suggested that PADMA 28 may have anti-inflammatory activity whose mechanism remains to be elucidated.



    In 2000 Suter et al showed the anti-oxidative mechanisms of PADMA 28 by proving PADMA 28 is an electron donor, binds (chelates) iron ions, reduces iron(III) to iron(II) and prevents DNA damage.



    In 1999 Ginsburg et al found that PADMA 28 impedes the laying down of plaque in the blood vessels . They found 4 inhibitory effects of PADMA 28. It was found to strongly inhibit (1) the killing of epithelial cells in culture induced by "cocktails" comprising oxidants, membrane perforating agents and proteinases; (2) the generation of luminol-dependent chemiluminescence in human neutrophils stimulated by opsonised bacteria; (3) the peroxidation of intralipid (a preparation rich in phospholipids) induced in the presence of copper; and (4) the activity of neutrophil elastase. They concluded that PADMA 28 might prove beneficial for the prevention of cell damage induced by synergism among pro-inflammatory agonists.



    Recently cell biologist Prof. Israel Vlodovsky, from Hadassah Hospital Israel, found PADMA 28 inhibits the growth of muscle cells in blood vessel walls, this study has yet to be published.



    Mechanism of Action


    So how does PADMA 28 work on patients with PAOD? By its anti atherosclerotic activity as the trials discussed have shown, decreasing atherosclerotic blockage of arterial blood to the legs thus increasing the amount of oxygen and reducing intermittent claudication. But as Matzner et al have said its anti-atherosclerotic mechanism remains to be elucidated.

    Whether it is one ingredient in the PADMA 28 or a mixture is also unknown, but at lease 3 of the ingredients have been used in ‘vascular medicine’ for generations, and may be the key elements in PADMA 28s mechanism of action.



    Saussuria is part of the Costus root, has been used for millennia in China and India as a tonic. Various fractions of costus oil have hypotensive activities, with 12-methoxy-dihydrocostunolide and the delactonized oil being the most potent, acting through direct peripheral vasodilation and cardiac depression.



    Myrobalan. Indian literature suggests that it is used as a cardiac tonic as it assists blood pressure.



    Red Sandalwood has been taken as a remedy in China since around AD500, and is still held to be useful for chest pain.



    Conclusion

    Alternative medicine is a rapidly expanding sector of medicine, and patients are more and more interested in it and how it can benefit them.

    POAD is on the increase and current therapy is very limited medically to very few drug therapies, which don’t work well, including prostacyclin and naftidrofurly, and surgery.

    PADMA 28 is a herbal formula proven to help intermittent claudication, with little, if any, side effects which offers safe and easy treatment, even though its anti-atherosclerotic mechanism remains unknown.

    With ongoing trials at Hadassah Hospital, Jerusalem and the Middlesex Hospital, London, it seems likely we will here a lot more about PADMA-28 especially with current studies on its effect on coronary arteries and its impact on cerebral arteries. And who knows maybe it will be the next aspirin, morphine or digitalis, all of which are based on traditional folk remedies!