Mechanisms to control tumour growth, including Melatonin and Diurnal Fasting

On scientific grounds and from what is now known of the multifactorial nature of the host-tumour relationship, cancer management must reflect a broad knowledge and understanding of the many factors involve. Thus, in addition to conventional options such as surgery, radiotherapy and chemotherapy, the inclusion of diet, nutrition, as well as evidence-based mind-body modalities etc strengthen the management – like sticks in a bundle. Optimum management should, therefore, incorporate the very best of what current medical science can offer to give the patient the greatest chance of cure. 

Tumour growth rate a balance

Tumour growth becomes a balance between the rate of cell multiplication or reproduction and the rate of cell apoptosis or cell death.  No growth or dormancy doesn’t mean no activity; only that there is a balance between these two processes.  Reducing the tumour using natural means therefore implies either discouraging cell reproduction or stimulating apoptosis.

He spoke about inflammation and decreased immune response as two important factors involved in tumour growth. Increased risk of malignancy is associated with chronic inflammation caused not only by certain infections, but also by chemical and physical agents as well as by autoimmune reactions.  Growth factor also increases.

A tumour 1 mm in diameter contains about 1 million cancer cells.  If it is to grow beyond this size it needs a blood supply (angiogenesis).

The role of inflammation

The most potent accelerator of cancer growth is inflammation i.e., the cellular and humoral response to tissue injury.

After tissue damage due to surgery, radiotherapy or chemotherapy, inflammation occurs and is a necessary component of wound healing where mediators of acute inflammation are designed to activate mitosis of normal cells as well as down-regulate cell-suicide (apoptosis). Cancer cells present either locally or remotely to the inflammation may also respond to these growth stimulants to switch off apoptosis resulting in cancer acceleration.

So during inflammation the rise in activity suppresses apoptosis and the tumour grows.  After the activity has peaked the cell reproduction is suppressed and the apoptosis is restored.

Another factor is that because injury promotes tumour growth, any external attempt to destroy the tumour results in cell injury, ie inflammation, so it can be counter-productive… However surgery can be beneficial overall if it is used to de-bulk the tumour.  In such cases steps should be taken to minimize the cell damage and new cell growth (eg by the use of platelet aggregating factor antagonists such as Ginkgo Biloba).

Recognition of the links between cancer and inflammation has implications for prevention and treatment. How can we take advantage of the presence of these two mechanisms of cell reproduction and apoptosis so as to optimize the chances of tumour destruction?

One of the key factors in cancer treatment is therefore to encourage apoptosis by controlling inflammation. If cancer patients have either acute or chronic inflammation anywhere in the body e.g. gastritis (stomach inflammation) due to Helicobacter pylori (which is an infection present in 20 to 30% of the population) then they may have difficulty halting the progression of their cancer. Helicobacter pylori can be easily detected, and should then be treated effectively with antibiotics.

The role of the Immune system

Traditional immunotherapy assumes the tumour is a foreign organism in the same way that transplanted organs are, and stimulating the immune system so that cancer cells could be more readily recognised by the immune system, should result in destruction of tumour cells or suppression of their growth.  But this assumption is invalid because it does not take account of the fact that, unlike incompatible transplants, which express antigens on the surface of the cells to enable them to be recognised as foreign and be rejected by the immune system, the ‘foreign’ antigens on cancer cells do not generally express tumour-specific antigens on their surface where they can be identified and signals sent out for their destruction.  Rather tumour antigens are present but are almost invariable in the nucleus, ie inside the cell surface.  Only when the cells are being destroyed are these antigens exposed, and the immune system can work.

The pursuit of this paradigm that sought hope in immunotherapy has been a major distraction in the search for a satisfactory cancer treatment. However, if apoptosis can be promoted then the immune system through the T cells, natural killer cells and macrophages can have a role by indirectly targeting sick, dying and dead cancer cells. Hence adjuvant cancer treatment should include methods to maintain the integrity of the immune system and macrophages and heighten general resistance. In contrast, the greatest stimulatory effect of immunity on tumour growth occurs in the up-regulation of the inflammatory response. Exposure to endotoxin, the cell-wall component of certain bacteria such as Escherichia coli, a common cause of urinary tract infection, can stimulate tumour growth.                 

Other useful mechanisms

If the immune system cannot be used to control cancer growth what mechanisms can be exploited to encourage apoptosis in particular and cancer in general?

There are two main mechanisms: the use of melatonin and the use of diurnal fasting.

Melatonin

Melatonin is a natural hormone produced mainly in the pineal gland in the brain. Its concentration in the cells rises and falls every day under the control of the pituitary gland.  Its average daily level is also highest in early development, peaking just prior to puberty then falling off gradually with age particularly after 40 so that it is very low at old age.  Its production is stimulated by the presence of light, particularly white light at the infrared end of the spectrum whereas wavelengths in the ultraviolet end of the light spectrum are more powerful in switching off melatonin than the red wavelengths. 

Melatonin is known to moderate inflammation and promote apoptosis.

It is the magnetic component of Electromagnetic Radiation that impacts on the receptors in the eye to activate the neurological signal. The pinealocyte is activated via a beta-receptor.  Persons on beta blockers e.g., propranolol, for certain heart conditions may experience sleep disorder because melatonin production can be blocked. However, this can be overcome to some extent by taking the beta blockers in the morning. Aspirin also inhibits melatonin production and if painkillers are necessary, then panadol can be used as an alternative.

To ensure that as much natural melatonin as possible is produced a person should get at least half to one hour of bright sunlight to their eyes each day (not behind sunglasses). Melatonin can be used as a supplement but care should be taken to ensure that the minimum effective dosage is maintained, e.g., 1-3mg, but no more than 5mg per day taken before going to bed. The effect of melatonin follows a bell-shape i.e., neither low nor high doses are as effective as maximum physiological doses. It has been shown that excess can be as ineffective as not enough, therefore, careful dosing is important.

Melatonin is beneficial for most solid tumours but should not be used by people with depressive disorders, epilepsy, children, adults under 35 years of age, people with lymphoid cancers, multiple sclerosis, thyroiditis, rheumatoid arthritis and any other auto immune diseases.

Controlled Frequency of Eating  or Diurnal Fasting

Another method of increasing the amount of natural melatonin produced is to restrict calorie intake by using a protocol known as Controlled Frequency of Eating or Di-urnal Fasting. This procedure relies on having very low calorie intake plus high fibre for 18 hours each day and obtaining the necessary caloric intake for energy expenditure in the remaining 6 hours. e.g.  Breakfast/Lunch at 12:00 noon and Dinner by 6:00 pm and then nothing but low calorie intake such as vegetable juice etc. until 12:00 noon the next day. Alternatively have breakfast and midday lunch while the evening ‘meal’ is low calorie, high fibre eg., fruit and salad in moderation.

This regime activates the adrenals to produce   cortico-steroids and DHEA that have anti-tumour effects coupled with stimulation of the production of melatonin in the gastro-intestinal tract via the enterochromaffin cells during ‘fasting’. The effects appear also to contribute to anti-angiogenesis i.e., help to stop the tumour from creating its own blood supply necessary for it to keep growing once it has reached a size of about 1 millimetre or 1 million cells. This growth restriction together with the apoptotic effect provided by the melatonin should favour tumour regression. It is important not to supplement with melatonin on top of the controlled frequency of eating regime as the effective dosage of melatonin could be exceeded.

Additional interesting information to come out of the discussion on controlled frequency of eating was that whereas some current dietary recommendations are that you should eat on demand or “graze”, this was not in the interests of maximising anti-tumour measures. This may also contribute to obesity because energy is being obtained constantly from food and not from consumption of energy stored e.g., as fat in the body. Perhaps the current concerns about the levels of juvenile obesity could be attributed to over-feeding babies during the suckling period when biochemical imprinting occurs to predispose to leanness or obesity. Research supports this hypothesis.

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