March 2001, Antoon Verhaak

SUPPLEMENTS AND DIET AS COMPLEMENTARY TREATMENT

Introduction

In 1994 I was confronted with Waldenströms Macroglobulanemia (WM). I was told that on the average I had six maybe ten years left, and that there was no cure.  The treatments that are available, often chemotherapy, in NL almost always Leukeran (chlorambucil) + prednison,  do some good, for some time, very different per person, by repressing the WM.  But they also have negative side-effects, which mostly grow worse the longer the drug is used.

After the first shock I revolted, and started asking, reading and consulting, looking what I could do myself to influence the progression of this WM.  Six months of searching later  I had made up my mind. There was no guaranteed  effective option, but there were some complementary  treatments or activities, that impressed me as promising.  Of course I stayed under supervision of my high valued regular specialist, dr. Jos Burghouts. Beside that I decided to invest in supplements and diet, under supervision of doctor Engelbert Valstar (a medical doctor and biochemist) who specialised in the effect of nutrition on cancer and was scientifically directed, having close contacts with regular medicine.  Furthermore I invested in exercise, tennis, cycling, running and more and more sailing, to enjoy my body and keeping it in good shape.  In the third place I invested in mind, under supervision of a trained psycho-therapist, who helped me to find my way through the distress and to fight for my life. Daily Zen meditation is part of that. All of this was before my contact with IWMF, in late 1997, which gave a major impulse to my knowledge about WM itself and many new treatments.

I am still very happy and grateful for these choices.  I think I have influenced the progression, but nobody can ever prove that.  I am sure however of their contribution to my quality of  life.

For me the major theme to discuss about nutrition and cancer is the question of proof, the scientific status of these. Is this just a hobby of mine, and of my nutritional doctor, is it just a belief, or is there scientific proof available or at least solid and rational indications?

I am intelligent and (long ago, but all the same) thoroughly trained in chemistry and in research design and statistics.  I view myself not as a professional scientist but as an understanding outsider and for sure as a rational man. But after choosing these yet unproven complementary treatments,  I found myself uncertain in discussions with unbelieving doctors and with other cancer patients who asked my advice.   Even in some IWMF publications therapeutic claims about supplements are described as quackery. 

The theme of this paper and this discussion is  the status of supplements and nutrition:  Is it quackery or is it a promising line of complementary treatment, well up on its way to be proved?

General remarks on supplements and diet

As far as scientific proof is concerned, there is a big difference between nutritional supplements and diets.

Whether supplements have real effect, whether they work, can be tested quite easily and cheaply.  Mostly they can be offered as a tasteless capsule, which could contain either the supplement or the placebo. If you have 200 people with WM and you want to test the effect of a drug, the most important things to do, are random and double blind assigning the drug and the placebo, 100 each, and register the course of the disease for all.

As I will show later, there is quite a lot of evidence of therapeutic activity against cancer of a number of nutritional supplements.

Concerning the use of diets things are much more unclear.  Direct scientific proof is almost impossible, requiring at least large scale, random assigned trials in which all participants closely follow the same regimen. This is not realistic, unless everybody is hospitalised and  forced to the same diet.

Here the only thing to do is make an inventory of what is already known, and let that guide you to realize some adaptations in your diet, of which you think that they will have effect, and, importantly also, which fit your taste.  Because a diet you hate, is difficult to hold on. 

The same is true for a naturopath or nutritional doctor who advises about diet.  Nothing is proven. Often such a person has a background in a culture or tradition.  For instance the long  tradition of  the ayur veda or the more recent macrobiotics. There maybe much wisdom in it,   (the aspect of consistency in advice for ages) but as far as I know scientific proof is absent.

There are some more general indications however which could direct you to adapt your diet. Indications…

(1)   from epidemiological data, like the occurrence and the rate of cure of cancer in people with different diets. The traditional Japanese diet seems to have very positive marks in this: Japan has the highest average lifespan in the world and a much lower incidence of cancer (which disappears when Japanese live and integrate in the USA),for instance breast cancer occurs less than 25% compared to USA, and moreover, Japanese women who do have breast cancer, have a 29% better chance of survival. (ref. 1 p 449). 

(2)   from research for single nutritional products.  You can add foods of which positive therapeutic effects are proven or are probable to the diet, and leave the ones with bad marks out. Besides those with a proven therapeutic effect, some others could be added of which a preventive effect is proven (like for vegetables, see ref. 1).  If a product strongly prevents cancer, that does not prove anything for therapy, but it is quite rational to assume that there is a much better than average chance that it has some therapeutic effect as well.

(3)   from a very long (thousands) list of randomised blind studies on animals, in which the effect of many nutritional supplements and diets has been tested on the survival of different cancers. As a result of these studies many supplements have been identified as being potentially therapeutic for human patients. By the way, exercise too came out as a factor in this. It is generally accepted that the outcome of such experiments on mice and rats has a strong correlation (up to .90) with the outcome of a comparable study on human patients.

(4)   from history, that is a personal point of interest of mine.  Humans have been developing and surviving during millions of years as collectors of vegetables, tubers and nuts, supplemented especially in the last periods with meat from hunting. Only during the last 10.000 years fat and proteins have replaced much of the old diet, and the variation of food, especially of vegetables has been very much reduced. Our body and resistance to diseases developed while our ancestors were fed with the old diet.

Looking into research concerning specific supplements

Many medical doctors oppose any nutritional claim by saying that never a real effect of any supplement has been proven.

Nutritional supplements are in this way pressed in the corner of alternatives and vague believers. Of course there are many unprofessional and even criminal therapists who use supplements and diet. But incompetent use by some, does not prove a drug does not work.

The question that counts is not “Is it alternative?”, but only  “Does it work?” This question should be answered by scientific testing of the effects.

The following section is based on a list of more than 100 references, compiled by dr. Valstar et al.   This list consists exclusively of international publications of randomised human trials, that were intended to test scientifically the therapeutic effect of varying supplements as complementary treatment of varying cancers. All publications can be found easily in Medline.  The list is reproduced in the last pages of this paper. To make it more accessible, I have reorganised the list in clusters of related subjects (same supplement or same cancer) as much as possible.

For this presentation I have selected some promising domains of research, to discuss in more detail.  In this discussion I will base on information from dr. Valstar and only refer to publications in English and in renowned international magazines.

First I will work out one nutritional supplement (PSK), to demonstrate that its therapeutic effect on several cancers is scientifically proven.  Then I will discuss some other supplements for which also several randomised trials exist, that are reported in renowned international scientific magazines.

PSK, an extract of Coriolis Versicolor

Maybe the most intensively studied case is that of PSK, the extract of  the fungus coriolis versicolor, related to shiitake.  Like with most nutritional supplements, for PSK are no indications of serious harm (10% of users complains about coughing and/or pigmented nails), so there seems to be no real danger in experimenting with it.

Coriolos Versicolor contains polysaccharide K (PSK), of which a significant positive effect on the time of survival and percent cure of several cancers was found in many experiments on animals (animal studies listed in ref. 2) and in at least 12 international published  randomised studies on human patients of cancer.  More trials were reported in the Japanese Gan To Kagaku Ryoko (ref. 14-18).

You can find the international references in the reference list numbered 2 to 12.  These studies concern cancer of bowels, stomach, gullet, breast, nasofarynx  and acute leukaemia. 

As early as 1970 the results were so convincing already, that the Japanese government PSK admitted for treatment of several cancers. 

For intestinal cancer stadium C (lymph nodes affected) a major randomised and double blind study has been reported in 1990 by Toriso et al. (ref 2) Their trial included 110 patients and they reported a significantly higher disease free survival.  Mitomi et al. (ref. 3) checked this up by another trial with 400 patients and reported in 1992 again significant therapeutic effects for the same cancer with PSK.

Four randomised studies (ref. 4-7) were reported  with PSK for cancer of the stomach. In all four, therapeutic effects were found, one non-significant and the others significant.

The references 8-13 report randomised trials with PSK for other cancers, mostly again with significantly positive effects.

Bladder cancer and supplements

Bladder cancer is often successfully treated by operatively removing the affected tissue.  The chance of relapse is very large however.  One trial is reported (ref. 19) in which an experimental group of patients, after operation, received a combination of four extra vitamins (A, C, E and B6) in megadoses, as a complement to the regular treatment. Compared to the control group the chance of relapse in 5 years proved to be reduced significantly (91 % resp. 41%).  Vitamin B6 was studied seperately in two trials of which one reported a significant positive effect and the other did not (ref. 20-21). Two other studies (ref  22-23) were  reported about the effect of a probioticum, lactobacillus casei. As in ref. 19 the chance of relapse (but now after 1 year post operation) was reduced significantly, in one report from 44% to 21%.  Moreover, the change to a more aggressive type of cancer, which is quite common in bladder cancer, was reduced markedly too.

Melatonin

Melatonin has been studied and rechecked in a number of studies, mostly as a complementary treatment with chemotherapy, in different cancers (5 studies are cited, ref. 24-29). In ref. 24 Lissoni, P, et al. report a significant positive effect of melatonin on the survival of patients with  metastatic brain tumours. In another trial the same researchers find  (ref. 25) a significantly positive effect of  Melatonin added to interleukine-2 for advanced tumours, compared with a control group with only interleukine-2. In ref. 26 they report significant improvement in cases with a (brain tumour) astrocytome grade 4.  In ref. 27 and 28(replica) they report significant improvement by addition of melatonin for non-small-lung cancer patients treated with chemo.

Folic acid (leucovorin)

A series of randomised studies (ref. 30-45) are reported for metastatic bowel cancer treated with the chemo 5-FU (5-fluoruracil) in which the effect of addition of leucovorin is tested.  A review of these can be found in ref. 30 (p. 224). The conclusion is a significant higher number of regressions, a slightly better one-year survival and no difference in survival after two years. The results of the same regimen, post operative,  for non metastatic bowel cancer were even better, as a significant decrease of relapse was reported in ref. 31 and 32.

What about WM?

Being a rare cancer WM does not occur in these trials.  Of course an attempt to prove effect will concentrate on one of the big cancers.  Just to be complete in this I will mention the five supplement-studies in doctor Valstars list concerning WM-related cancers.

Ref 11 reports a better survival with PSK for acute leukaemia. Ref 47 reports an effect of vitamin A, that slows down the progression of chronic myeloid leukaemia, and ref  48 reports better survival with nocardia-extract for myeloid leukaemia. Ref  49 reports that addition of thymostimulin (thymus) gives significantly more regressions for NHL of intermediate and high malignity.  Ref  50 reports better survival of NHL patients with treatment with the  Coley-vaccine

Conclusion

The studies mentioned above are just a small part of  the total concerning supplements, but these studies are performed according to the highest scientifical standards and give an impression of the status of research. 

Having read this, I think one cannot seriously defend the stand that nothing has been proven.  For PSK, I think the existence of an effect is really proven, although much has to be done to learn exactly the how and when. But also for bladder cancer and the other supplements discussed above, the indications are strong, and quite a lot of testing has been done.

On the other hand it is clear also that research and testing of these have only just started. 

Most work has yet to be done.   I hope that the promising results of these first series of trials on supplements, will trigger a mass of  new research.

Which supplements and diet do I use now?

List of supplements advised by doctor Valstar and used at this time (march 2001)

Thymus concentrate  600 mg                               2*d

Alfacalcidol         0,25 microgram                        2*d

Shiitake extract    600 mg                                    2*d

Bromelain            500 mg                                    3*d

Resveratrol forte  100 mg                                    3*d

Genistin                250 mg 35% extract                4*d

Aloe vera extract    25 cc                                    1*d

Pau d’Arco           500 mg                                  2*d

Orthocarotene         40 mg                                  1*d

Ortho-oxidant        900 mg                                  1*d

Vitamin E               400 IE                                   1*d

Sodiumselenite     1000 microgram                      1*d

Ginseng                120 mg (G2001 extract)          1*d

Bioquinon Q10                   30 mg                       1*d

Candinorm (Lb acidofilus 60 mg, apricotpowder 100 mg, etc)                                                              1*d

Limited extra vitamin C in some of the capsules

Furthermore:

Codliver oil        50 cc per day

Combucha tea  150 cc per day

Iscador              3%           20 drops per day

Flaxseed oil           15 cc per day

Some indication of the diet advised:

The diet should be rich of:

Boiled and raw vegetables, fruit, especially tomatoes (lycopene) and broccoli, soya, fatty fish, green tea, whole grains, some olive oil, some spices as curcuma, etc.  

And none of  or low in: animal fats and/or meat, other fats, roasted or fried food, milk(products), sugar, salt, artificial additives and so on…  

A selection of studies that support parameters in this regimen

This regimen does look quite alternative indeed. 

When I met dr. Valstar for the first time, I was really hesitant therefore.

He convinced me, then, that there were serious indications for all key products, and moreover, that it made sense in my situation, to use a list of potentially active and harmless products. 

If only one of the list would be really effective, all of it would be worthwile.  The image of hunting with a shower of shot.  But Valstar was convinced that much more than one of this list would contribute to effect.  In the following I will pursue this matter further. 

When I almost had finished the writing of this paper, I decided to ask dr. Valstar to give his arguments for at least some important foods or supplements of my personal regimen. 

So what follows is not at all complete, just some indicative information about some foods. 

It is a combination of what I knew already and of what Valstar contributed on my request, at this short notice.  Valstars criterion to prescribe a nutritional supplement for WM,  is that there must be effect or serious indication for effect in NHL, MM or leukaemia.

 

Thymus concentrate.    See ref. 49 (on NHL) and 54 to 61 of the list of literature.  Beside this there is much more literature on human and animal studies of thymus.  Thymostimuline is the active compound in thymus concentrate.

Alfacalcidol                  (the direct precursor of) vitamin D3.  See ref. 103.  In a randomised trial significant effect on survival was found for vit. D3 on myodisplastic syndromes (MDS).  Here also many other publications about vit D3 and cancer.

Shiitake extract            This is a (much cheaper) cousin of the effective PSK.  On Shiitake itself see ref. 51-53.  There is much more publicated than this.

Bromelain                    In ref. 108 is reported that bromolain promotes differentiation in different types of leukaemia

Resveratrol forte          In ref. 104 is reported that resveratrol (a natural product present in wine) inhibits the growth of THP-1 human monocytic leukaemia cells in vitro, probably by inducing apoptosis.

Genistein (soya)           Ref. 106 reports an in vitro study which shows that a key factor for promotion cancerous growth in NHL is inhibited by genistein.  Ref. 1  (p. 455) reports a number of studies on effects of genistein on several intermediates in the development of prostate cancer.  About genistein  much has been published, and much has been argued already.  Valstar is convinced of its positive contribution against progression of cancer.

Sodiumselenite             The Dutch soil is poor in selenium, which (in epidemiological studies) is shown to have (below the limits of toxicity) a preventive effect on certain cancers.

vegetables, fruit            See ref. 1 for an impressive survey of many studies about preventive effects on cancer. Their preventive effect is generally considered proven

fatty fish                       See ref. 105 for a report on studies concerning omega-3-fatty acids (much present in fatty fish), which in vitro prove to have cytotoxic activity in myeloma cells of mice. About these specific fatty acids much more has been published.

Lycopene                    See ref. 86.  Much more is published about it. Valstar considers it as a key-parameter.

Curcuma                      No concrete references available, but several human trials have been done which find significant therapeutic effects in throat cancer.

Green tea                    See ref. 109, which I got from Matt Dennis!  Reported is an in vitro study in wich EGCG, a main constituent of green tea, inhibits the growth of leukaemic cells.  Ref. 1 gives much information about this also.  There are many more studies about it, but a lot of controversy also

Olive oil                       Proven as having an preventive effect (see ref. 1).  Indications about possible therapeutic effects on cancer are weaker, up to now.

Iscador                        Ref. 107 reports effect in vivo and in vitro against lymphoma.

Q10 and Ginseng         Prescribed to lessen fatigue, but for these there is some indication of therapeutic activity also.

Carotene                      A major study found no positive effect, but Valstar disputes its design

Personal conclusions

It is clear that the therapeutic effect on WM of my nutritional regimen, given above, is not proven.  But there are serious indications.  Some are described in the sections before and after the regimen, more can be found in the medical literature and besides there is a mass of animal research. Moreover there are the theoretical considerations and the experience of dr. Valstar

In 1994, after the diagnosis of WM, it was a question of choosing the best option in a very negative situation.  This line impressed me, but did not convince me completely.  But it was (beside exercise and mind) quite clearly the best of the options that I found on my path.

In 1994 the key-point for me was the professionalism of dr. Valstar, who impressed me by his knowledge of nutrition and cancer and by his scientific and critical attitude. 

In fact he agreed that this diet and this list of supplements has not been proven, but just the best to do until more was known.  There was no danger in this list for toxicity,  I checked up that. dr. Valstar made his selection from the products for which a stronger or weaker indication existed that it effects WM.

Not proving anything, but adding to this, was and is the impression of his results.  Since about 15 years he has advised cancer patients, who often only come to him after all regular options failed. Yet he counts an unexpected high number of regressions and ‘spontaneous cures’. And most of his patients live longer, often much longer, than their medical prognosis indicated. 

And last but not least, looking back now, I find myself much more convinced than in 94. It seems that everything in which dr. Valstar is involved, turns the favourable direction.

For myself, all symptoms I had in 94 disappeared within half a year, except part of the fatigue

My IgM was at diagnosis 3300, stayed three years under 4000 and climbed slowly up to 5900 now.  My Hb was and is slightly under normal, other values are normal. My hematologist proposed to start treatment in 94 but agrees up to now with W&W. So things go better than I could hope then.  But this is no miracle, WM can develop like this, sometimes.

One year later, at the end of  95, one of my best friends, Kees, got throat cancer, a big tumour with lymph nodes affected, and was sent home to die.  Kees copied my choices and has been cancer free now for three years.  At that point I got convinced, this was too much coincidence. 

Kees is a filmmaker, and we decided to tell our story in a TV film.  I have the English version (‘The Will to Live’) with me for those interested. 

An 8 year old girl, Shifra, with acute leukaemia and using Valstars supplements got involved in the film too.  After joining us she relapsed four times, apparently because of a genetic defect producing leukaemia cells again and again. Up to now, three years later, she has still survived. At this time she normally attends school.  The doctors say that they have never heard of such a case.    

My father in law has metastatic prostate cancer.  He has been using Valstars products since a year and is doing very well up to now. 

In 96 the little daughter of my tennis friend Peter proved to have the terrible disease cystic fibrosis (no cancer). Peter asked Valstars help too. Valstar did some research and consultation about CF and nutrition, and gave him a advices. After five years Peters daughter is doing much better than usual, her doctors are surprised. And to be clear, these cases are all cases, it is not that there were others in which the results were negative    

This all is no proof, just some stories, but it is happening close to me, and impresses me, as you will understand.

So, all in all, I am convinced, not of a miracle, but of something that makes sense. 

Antoon Verhaak march 2001


List of literature   

Comprehensive regular handbook on the relations between nutrition and cancer, with theory, epidemiological data, reports of trials etc.

1.                  Nutritional Oncology, D.Heber et al. 1999, Academic press, San Diego CA  

In the following list, nrs 2 to 102, (compiled and kindly put at my disposal by dr. E. Valstar, et al.  Den Haag NL ; for fraternal discussion only: redactie@kanker-actueel.nl and Kees will forward to doctor Valstar) only randomised studies on human patients are recorded, which evaluate the therapeutic effect on one or more cancers of one or more nutritional parameters. Except four or five, all report positive effects (the list is not selected by outcome). Many more studies have been reported for these supplements on animals (mostly rats and mice).  These are not listed here, but can be found often via the reference list of the (human) studies listed below.

Of all publications listed here, an abstract in English can be found easily on Medline.

Publications in English on PSK and several cancers

2.                  Toriso M et al ; Cancer Immunol Immunother 1990 ; 31 : 261-8.

3.                  Mitomi T et al ; Dis Colon Rectum 1992 ; 35(2) : 123-30. 

4.                  Nakazato H et al ; The Lancet 1994 ; 343 : 1122-1126

5.                  Nio Y et al ;Biotherapy 1992 ; 4:117-28

6.                  Niimoto M et al ; Jap J Surgery 1988 ; 18 :681-686

7.                  Kondo T et al. Biotherapy 1991 ; 3(4): 287-95

8.                  Lino Y et al ; Anticancer Res 1995 ; 15 : 2907-12

9.                  Toi M et al ;Cancer  1992 ; 70 : 2475-83

10.              Go P en Chung C-H ; J Int Med Res 1989 ; 17 : 141-149

11.              Nagao T et al ; Tokai J Exp Clin Med 1981 ; 6 : 141-6 

12.              Ogoshi K et al ; Cancer Investigation 1995 ; 13 : 363-69

13.               Ohno R et al ;Cancer Immunol Immunother 1984 ; 18 : 149-150

Publications on PSK and several cancers in the Japanese scientific magazine  Gan To Kagaku Ryoho

14.              Nakazato H et al ;Gan To Kagaku Ryoho 1989 ; 16 (8Pt1): 2563-2576.

15.


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