Urine therapy in Ayurveda: Ancient insights to modern discoveries for cancer regression.

Investigation of spontaneous regressions (SR) of cancer may explain host mechanisms of control by anticancer substance (A.C.S.). Documented human SR, of bladder cancer after uretero-sigmoidostomy and of uterine leiomyosarcoma after irreparable vesico-vaginal fistula, suggested the presence of A.C.S. in human urine. Animal experiments with urine in rat alveolar carcinoma and in mouse melanoma point to A.C.S. Urine therapy, as cited in Bhrigu-Samhita and used in some cases, needs to be followed up by systematic Reverse Pharmacology and analytical identification of A.C.S.

“The problem is not what makes the cell divide, but what has gone wrong with the mechanism so that it cannot stop? A cancer cell is comparable to a car on a slope. If it starts running, the question is not what makes it go, but what's wrong with the brake?” – Albert Szent-Gyorgyi (Nobel Laureate) [1].

Cancer, in its diverse forms, continues to be a formidable therapeutic challenge, notwithstanding significant advances in cancer cell biology and molecular oncology. Malignant melanoma is a feared tumour due to its invasive nature and a relative resistance to chemotherapy. It is surprising to note that well-documented spontaneous regressions have been reported in patients with malignant melanoma and in other types of cancer [2], [3]. Spontaneous regressions of cancer, though rare, are ‘Nature's whispers' which compel us to search for the mechanisms which underlie such phenomena. However, it is well nigh impossible to organize randomized double blind trials to investigate the veracity of such rare regressions or to identify the responsible mechanisms in individual cancer patients. Are there any alternate paths to study this problem with vignettes, case profiles and qualitative research?

In the year 1966, I was reading a review by Everson on case-reports and vignettes of patients with well-documented regression of several types of cancer [4]. What impressed me most was the vignette of 13 patients with cancer of the urinary bladder that had shown a regression, on a follow up cystoscopy, after uretero-sigmoidostomy. Everson and Cole proposed that the regression, after diversion of the urinary stream before cystectomy, was due to the lack of the continued presence of the carcinogen in the bladder [5]. But this explanation does not stand to reason. This is because, as per the sequence of carcinogenesis, once a tumour is induced the presence of the chemical carcinogen is no longer needed. I instead proposed, in 1966, that a putative anti-cancer substance (A.C.S.) is excreted in the urine which has a low renal threshold and is not reabsorbed by the renal tubules. As a consequence, A.C.S. could never reach effective and sustained plasma/tissue levels to be effective against cancer (Fig. 1). But with the urinary diversion into the colon, A.C.S. could be reabsorbed continuously into the systemic circulation and hence reach adequate levels and precipitate a cascade of tumour regression [6].

Fig. 1

The diary record of the hypothesis on 20th April, 1966.

The very next year-in 1967 – I went to the Yale Medical School as a Merck International Fellow in the Division of Clinical Pharmacology and Cancer Chemotherapy. There I found, in the hospital archives, a case report of a patient with leiomyosarcoma. After surgical removal, the tumour did not recur over the years. However during the same period, she had developed a postsurgical vesico-vaginal fistula, which could not be successfully repaired after several attempts. Later, when the fistula was finally successfully repaired the tumour came back with an aggressive vengeance and patient died with widespread metastases. This supported the argument of a systemic absorption of A.C.S., from the vaginal mucosa, due to the irreparable fistula, and consequently a long term suppression of tumour. Once the fistula was repaired and there was no leakage of urine into vagina the tumour was not suppressed by A.C.S., unavailable systemically. I also, then, studied all the extensive literature on cancer-promotive and regressive substances in tissues and biological fluids [7], [8], [9], [10]. I came across the seminal work, by Williams and Waters, on human urinary extracts inducing tumour regression of Twort alveolar carcinoma in rats [11]. The work done by Albert Szent-Gyorgyi and colleagues, on the anti-cancer-retine- from tissues and human urine, became known [11], [12], [13], [14]. But their focus was only on the keto-aldehydes and methyl glyoxal in urine extracts. The isolated compounds lacked anti-cancer activity. This led to a general apathy and disinterest in these remarkable findings by a Nobel Laureate and his colleagues.

I was aware that the book ‘The Water of Life’, by Armstrong, had inspired many abroad and also in India to pursue auto-urine therapy movement. There were claims of cancer regression with urine therapy in the lay press and in many books [15], [16]. As a clinical pharmacologist, I was quite wary of some of the tall claims and also of a heavy endorsement of auto-urine by a freedom fighter and later the prime minister of India-Sri Morarji Desai. He ascribed his being in pink of health, in his eighties and nineties, to his long practice of auto-urine consumption [17]. There were also several meetings and conferences on auto-urine therapy in India.

There are references in the classical texts of Ayurveda on urines from eight animals, including from humans [18], [19]. Their properties and activities are different based on the source. A very interesting reference to human urine as a treatment of cancer is described in a manuscript – Bhrigu Samhita. The shlokas run like this: “After going to the urinal, one should collect one's midstream urine in a clean vessel. One should take 1 to 2 tola of urine on a fasting stomach for the duration of one mandal (circa 42 days). The regimen of pathya diet and healthy life style has to be followed” [20]. There is also a chapter on auto-urine therapy in an ancient manuscript of Yoga –Damar Tantra, published by Athavale in an Ayurvedic journal (1960) [21]. The instructions are similar to those given by Bhrigu. However, the verses numbered 22 and 23 are relevant in view of a case described (vide infra). Therein it is stated that if auto-urine is taken for six months continuously with Amruta (Tinospora cordifolia nee glabra) mixed in urine, it will make the person free of serious diseases and s/he will be healthy and happy. There is also a documented centuries-long and current usage of auto-urine drinking in Buddhist and Yogic traditions. This is said to improve resistance to diseases and a sense of well-being.

There are thousands of small molecules in urine. As a consequence, it is not easy to isolate and identify the specific anti-cancer bioactive. The variability of these ingredients, based on diet, exercise and life-style, is an added challenge to research. In addition, there is a repugnance to urine therapy for aesthetic reasons and due to its smell and taste. This has naturally prevented a serious interest in the domain. But I felt that there is a need to at least to study this further. This can be first done experimentally and then in case reports/vignettes. To neglect all the aforesaid hits/leads by reputed scientists and shastras would not be fair. We should miss out any chance to understand the host mechanisms for cancer control which may help patient care.

At Yale, I learnt from Dr van Woert (a pioneer in l-dopa therapy of Parkinson's disease) and Dr Sartorelli (a leading onco-pharmacologist) how to transplant melanoma in mice. Then I carried out a preliminary experiment, which I love to share after many years. My mentor Dr Robert Levine (medical ethics guru) and Dr Arnold Eisenfeld (discoverer of oestrogen in the hypothalamus) were quite supportive to let me test the idea in their laboratory. Black male mice C57 BL/10 (n = 23) were received from the Jackson Laboratories, Bar Harbor, Maine. These were housed and taken care of with good laboratory practice. The mice were transplanted with uniform pieces of B-16 melanoma (circa 3 mm in diameter) subcutaneously, with a trocar and cannula. The control group (n = 11) and the treatment group (n = 12) were housed in metabolic cages (3 mice/cage, except in the last control group-2/cage). The access to food was kept overnight only. The collection of urine, cleaning of cages and weighing of mice were as per standard procedures. The urine was collected for 6 h in centrifuge tubes, covered with aluminium foil. The tubes were kept on ice in glass beakers. In the treatment group, 0.5 ml of pooled urine (from the same cage) was injected intraperitoneally with a sterile syringe. The control group received 0.5 ml of normal saline i.p. The tumour size on the marked animals was measured with a calliper for the diameters, carefully, basally and every three days,. The animals were observed for morbidity and mortality. The statistical analysis of the data on body weights and tumour size was carried out with Student's ‘t’ test.

The increase in the mean body weights of the control group and treated group were not significantly different. Fig. 2 shows the values of the mean tumour volumes of melanoma. These were 12.87 ± 1-61 (S.E.) cm3 in the control group and 8.56 ± 0.69 cm3 in the treated group The difference is statistically significant (p < 0.05). Though the tumour volumes were reduced significantly in the urine-treated group, there was no significant prolongation of survival. It is likely that only a single injection/day may not be sufficient to have adequate and sustained levels of the putative A.C.S in the plasma to influence a stronger regression and better survival. And unlike the earlier positive studies with extracts, the whole urine used in the experiment may not contain sufficient quantities of A.C.S.

Fig. 2

The difference in melanoma volumes between the control and auto-urine treated groups (*p < 0.05).

It is of interest to note that, in a case series from Germany, Novak has shown significant regression of cancer, on radiography, with ether extracts of auto-urine a), b), [22]. Autourotherapy in general practice and its status and future prospects were discussed in Germany in the mid-sixties a), b), [22], [23]. One would also cite a case of a 56 years old woman who was diagnosed to have ovarian cancer at Sir Harkisandas Hospital (HN 9252744). Her CEA- 125 was 300 (normal range 0-35u/ml). The histological diagnosis was moderately differentiated cystadenocarcinoma of the left ovary. She had ascites and the fluid showed adenocarcinoma cells. She was treated surgically and with cycles of follow up chemotherapy. After two years, she developed inguinal lymph nodes. She had endometrial cancer. She was treated conventionally with surgery followed by radiation and chemotherapy at Tata Memorial Hospital (Tata BJ 15570). She developed ascites. She got radiation burns and as there was no response in her ascites, she abandoned the treatment. She changed her diet and reduced her food intake. She took simple diet of mung, soups, milk, vegetables and figs. She started taking orally her own fresh filtered urine (15–30 ml) five times in a day initially. Later she reduced the dose to three times in a day. In addition, she collected one foot long fresh thumb-size stems of Amruta (T. cordifolia nee glabra) and cut them into 4 to 5 pieces. These were soaked into water (1- 1–5 L) and lightly boiled like a tea. She drank only this tea throughout the day and no water. She was doing this regularly for the last two and half years, after her discharge from the hospital. Her ascites had disappeared and she had no symptoms or signs. When we interviewed her, she appeared completely healthy and cheerful. But was she not ready for any further investigations.

Another patient with ovarian cancer was seen with a survival for six years. In addition to the conventional treatment, she took auto-urine and T. cordifolia in a lesser dose than the case cited above. Her quality of life remained amazingly good, despite the chemo sessions. She continued her professional consultancy throughout the period. Terminally, she developed metastases only in the lymph nodes and not at all in bones, brain, liver or lungs. T. cordifolia contains a phytoactive called octacosanol that is a potent inhibitor of vascular endothelial growth factor (VEGF) and angiogenesis [24]. It has been shown elegantly that VEGF is the specific growth factor for angiogenesis that assists the spread and growth in parenchymal organs. Whereas its spliced version VEGFc is specific growth factor for lymphangiogenesis which is needed for the cancer to spread and grow in lymph nodes [25], [26]. Recently, from our laboratory, Paradkar has shown that the extract of T. cordifolia inhibit the migration of cancer cell lines and also reduce their induction of angiogenesis in the chick chorioallantoic membrane [27]. T. cordifolia (Fig. 3) has been shown to possess immunopotentiating and, increasing colony growth stimulating factor activities by Thatte et al. in Dahunukar's group [28]. Anticancer properties of the plant have also been shown in our and other laboratories [29].

Fig. 3

Guduchi (Tinospora cordifolia Willd.)

The literature on the anticancer and other properties of auto-urine therapy needs a critical review [30], [31]. The use of cow urine, its distillate and Panchgavya is becoming quite widespread. As a consequence, the lay public does not have proper guidance. There is a need to generate reliable data on urine therapy from studies with Ayurvedic Pharmacoepidemiology, Observational Therapeutics, Reverse Pharmacology, Systems Ayurveda and Integrative Oncology. Cancer patients are often desperate to try any unconventional and traditional remedy claimed to be useful. There is a need to caution that sometimes such attempts may deprive the patient of availing of a management protocol that is curative/palliative or they may even run the risk of hazardous side effects. I was told by a leading cancer surgeon- Dr Praful Desai that he has seen hyperkalaemia in a cancer patient who did not let go of a single drop of his urine undrunk in 24 h! The only wise path is not to take extreme positions as to urine therapy but to explore Ayurvedic wisdom with an open mind and investigate the vignettes with a rigour of scientific reproducibility.

Sir William Osler reported several cases of spontaneous regression of even metastatic breast cancer [32]. He, said, “No condition, however desperate is quite hopeless.” At the conference on spontaneous regression of cancer, echoing this spirit of a pioneer at his institution, Dr Srsic, from the Johns Hopkins University School of Medicine said, “Cancer will be conquered in our lifetime … Spontaneous regression implies something has happened within our body to cause the disease to cease. If we can find out what that something is, we may understand what is needed.” [33].

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