Nutrients for Cancer

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Doing medline searches following the pattern of "mice cancer [nutrient]" yields great results for determining how beneficial a nutrient might be in treating cancer. Just as importantly as taking the right compounds is taking the right dose, which is where most people fail. So the following are the best compounds for existing cancer I could find based strictly on mice or rat studies. The doses are for treating existing cancer. Half the doses might be great for prevention. The indicated doses are based on a 2000 calorie human diet, and are very close to doses used in on-going human trials. The nutrients in the list each had at least a 50% reduction in tumor size, number, and/or metastases (compared to mice with the same cancer, not a direct percent reduction). A 50% reduction may correspond to a doubling of remaining expected lifespan for terminal cancers. The hope is that the percentages correspond to increased lifespan, and that the effects are additive. Taking half the dose usually causes the cancer to grow twice as fast as the full dose, so the amounts are important. Eating 30% fewer calories (or exercising to burn away 30% of the calories consumed) directly slows cancer down by 30% and also increases the concentrations of these doses in the blood. This has a bias towards lung cancer. There are a couple of other options for breast, prostate, skin, and colon cancers like soy products, beta-sistosterol, curcumin, and resveratrol (see discussion below).

Here's the summary:

All fats from fish oil, at least 50 grams per day (20% of daily calories) $4.50/day
12 Green Tea Extract with caffeine (6,000 mg) * $1/day
12 Grape Seed Extract (3,000 mg) * $2/day
8 Berberine (2,000 mg) $2/day
4 pomegranate extract (1,600 mg) $2/day
2 to 4 teaspoons cinnamon
Basic nutrition: 1 vitamin C twice a day (2,000 mg), 1 vitamin D (5,000 IU), 1 vit B50 complex
As much of the green tops of broccoli as possible.
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40 pills per day, about $360 a month. This is possible if pills are divided into 4 sets of 12 taken every 4 hours. If fewer pills are desired, skip methylselenocysteine.

Most of this is tart flavonoids which can be difficult to tolerate, especially without food and milk and the doses have been reduced to be the bare minimum that can duplicate the mouse studies. They definitely need to be divided up into 4 doses per day.

Broccoli and Citrus pills may be great, but they are not standardized extracts, so simply eating the darkest color parts of these plants (like the skin and seeds of tangerines) may be just as good as taking 20 each of these pills per day.

Compounds that appear great but are not available to the public: Betulinic acid, deguelin, silibinin, certain compounds of broccoli (the extracts do not seem to have enough), Ginsenoside Rg3 from ginseng, and certain soy genistein formulations.

Compounds that do not have strong enough evidence yet for most a wide range of cancers but may work well in specific cancers: IP6, selenite, methylselenocysteine, soy and genistein.

Compounds that may work on certain cancers by direct contact like skin and colon, but are otherwise not bioavialable in humans: curcumin, resveratrol. Curcumin maybe in prostate and pancreas when combined with a liposomal carrier.

Compounds where the situation is complex and I need to study: I3C (estrogen problem?), vitamin E, vitamin A, and the flavonols quercetin and kaempferol, and soy isoflavones.

Here are the details
Total intake of flavonoids (as in this list of cinnamon, grape seeds, green tea, and pomegranate) in humans is normally around 0.05 g/d, but the mouse studies show good reduction in tumors at around 5 to 10 g/d (converted to human dose). A "paleolithic" diet did not have fertilizers and genetics to reduce the nutrient density provided 1 g/d. For example, our ancestors received 20 times more vitamin C. The mice studies show that 5 times more than this paleolithic normal is required for flavonoids to seriously slow cancer. There are 4 different classes of flavonoids suggested, so taking all of them could result in about 15 times more than the paleolithic normal which increases the chances of toxicity. Since these are natural and common compounds, the toxicity should be mild and reversible.

green tea extract with catechins 6 g
20 weeks after BaPat lung cancer inoculation, 1% in diet in diet of 65% EGCG (equiv to 1.5% in water tea solids) for 25 weeks gave twice as much in blood and lung tissue compared to 0.5% in water. This resulted in 10 times fewer large and medium tumors, but not a change in the number of tumors, indicating growth rate was slowed. In another study 0.5% in drinking water of the same extract extract was started 20 weeks after NNK lung cancer inoculation and lasted for 32 weeks resulting in 50% fewer adenocarcinomas developing.GTE has Flavonols: quercetin, kaempferol, myricetin like capers. The EGCG (a flavAnol) does not work without the catechins (another flavAnol). One study thinks catechins in green tea extract might allow curcumin to finally work in vivo. Curcumin is not otherwise bio-available in pure form. Only 3% of 30 men with neoplasias got prostate cancer after one year at only 600 mg/d, verses 30% of controls. 12 weeks at 6 g/d in human mouth pre-cancerous lesions resulted in 59% fewer cancers. Half the dose had only 38% reduction. At 4 g/d 66% of leukemia patients with palpable adenopathy had at least 50% reduction.

grape seed extract 3 g
0.5% in diet in mice resulted in 60% smaller tumors when started 29 days after inoculation (2 years in people?). 2nd study with similar results. The proanthocyanidins worked on all 4 NSCLC cell types and mutations thereof. Grapes contain anthocyanins (like berries, cocoa), proanthocyanidins (like apples, cinnamon, cocoa, pycnogenol), and catechins (green tea) so benefits may overlap. It does not have the flavanones (citrus), flavonols (capers and tea extracts), nor certain special non-flavonoid compounds that are in pomegranate and broccoli. Resveratrol with this won't hurt, but it is bio-unavailable unless it can come in contact with the cancer ( G.I. and use DMSO transport for skin and prostate). Resveratrol should be kept to less than 0.5 g/d to prevent ligament and tendon injury.

Pomegranate extract 1.6 g
The 0.2% in water lab-performed extract was fresh but not concentrated, intended to simulate 2 whole pomegranates in humans, and resulted in 50% smaller tumors in NSCLC mice. 2nd study: 65% smaller lung tumors that were induced (non-human), same dose: 0.2% in drinking water. Pomegranate has a large component of ellagic acid and punicalagins but it may overlap with other flavonoid nutrients because it has catechins, gallocatechins, and anthocyanins (the only flavylium). It

Berberine 2 g, $0.70/day.
0.2% diet in mice resulted in 80% smaller NSCLC tumors (started before the NSCLC was injected). Also works to stop proliferation. Numerous studies. 10 different cancers tested in vitro so far in 2011. Bioavailability unknown. This is really too early considering the expense, but the dose is so much smaller and doable that it is hard to ignore.

Cinnamon 2 teaspoon/day. It has 2 times more proanthocyanidins (i.e. polymers of catechin flavAnols) than grape seeds, and these worked very well on NSCLC. Oral 400 mg/kg mouse (4 g per 70 kg human) weak extract for 30 days given 10 days after melanoma inoculation gave 50% reduction compared to controls. Also tested in extensively in liver and 1 study in colon.

fish oil 6% or 8% by weight of diet caused 50% reduction in adenocarcinoma, improved NSCLC chemo. Another study: "fish oil supplementation [10% => about 50g/day per 70 kg person] was able to decrease lung tumor [in mice] prevalence by 78% and 80%". This is well-studied. There is Coromega who supplies it in 2,000 mg citrus squeeze packets that tastes good so that 60 pills are not needed.

methylselenocysteine 3,200 mcg, 16 per day, 60 per day to being with. 70% smaller prostate tumors in mice. In test tube only for lung cancer, but bioavailability seems reliable. Potentially toxic at these levels, fingernails and hair. Likely to work differently than plant compounds therefore better chance of being additive effect. If there is one pill in the list to skip, this is probably it.

Vitamin D, 1 per day 5,000 IU to be sure to get proper amount. ( 25 micrograms per 1,000 IU).

Vitamin B50 complex 1 per Same reason as for vitamin D.

Vitamin C 1,000 mg 2 to 4 times per day. Same reason as above.

Zinc causes nausea even at low dose, so it's not included.

Vitamin E 1.6g (1,600 IU)
[it's possibly already in the recommended fish oil for preservation] Negative studies have come out on this, but 100 mg/kg mice (1 g per 70 kg person) had 60% less lung cancer when treatment started 4 months after cessation of smoke exposure. Quercetin had no effect. 450 mice, 2008 study. Evidence is weak for this one due to this one study, but the pill load and cost is small. Needs more study before listing.

Caffeine 0.600 g (4 strong cups coffee)
0.044% in water seemed to have a 50% effect in tumorigenesis and post-tumor metastasis and mice weighed 10% from less body fat. 0.02% in drinking water had no effect in another study that observed green tea benefits. 0.02% in water in another study had no effect.

Silibinin (from milk thistle) 0.3% in diet in mice caused 36% and 50% reduction in tumor multiplicity and adenocarcinoma. 2nd study, 1% diet caused 50% reduction in medium tumors, and 37% reduction in large tumors. 3rd study, 0.1% diet had no effect in lung cancer. 1% would be 5 to 10 g/d. Additive effect with I3C in study. Does not appear to be easy to find.

Deguelin at 0.07 g per 500g diet reduces lung cancer load by 80%. Many cancers studied. Very powerful, low toxicity, but not apparently available. LD50 in humans 10g to 100g per day. Rapidly decomposes in light and air. Tephrosin & rotenone are co-existing rotenoids are very toxic (parkinsons) LD50 at only 30 mg/70kg.

Broccoli Extract 1 pill is supposed to be 100g of broccoli tops, but extracts contain only 2 mg sulforaphane and similar compounds at 5 mg. The tests in mice were with 100 mg to 500 mg equivalents. 50 pills seems unreasonable, although 5 kg of broccoli tops is not much more tolerable. Sulforaphane, phenethyl isothiocyanate, and Benzyl-isothiocyanate (0.1 to 0.3 g per 500g) as other cruciferous vegetables and are studied extensively in prevention and moderately in reduction of smokers' lung cancer. Also lung metastasis from breast cancer. Has some flavonoids, but this does not appear to be the main benefit.

Citrus peel and seeds In keeping with the evidence above, similar effects are seen with various citrus compounds, but there are no standardized extracts. 5 g/d of the "Citrus Bioflavonoid Complex" would be good, but this may not be better than simply eating 1 peel per day. The peel and seeds without much of the pulp of just one or two dark oranges, grapefruit, and/or tangerine are probably best. One peel 3 times a day would be best. These are Flavanones that do not overlap with the other flavonoids listed here.

coconut oil to avoid carbs and increase energy, but not at the expense of fish oils and olive oil.

Vitamin C I.V. in pancreatic cancer mouse model kept tumors 3 times smaller, but survival was not increased. Similar results in other studies in mice. Good alternative to radiation and chemo treatments that are being used merely to reduce the size of the tumors and therefore pain but not extend lifespan. Oncologists call this "response" to the treatment, so remember "response" does not mean an increase in lifespan. Same with Vitamin C I.V. The goal is pain reduction without chemo and radiation.

Ginsenoside Rg3 from Ginseng. This is not yet available to the consumer. Ginseng extracts may help since people taking ginseng life-long have much less cancer, but there is not enough reason to believe relatively therapeutic doses can be achieved with current preparations. 0.3g/kg mice (2 g per 70kg person) of lipid soluble ginseng extract stopped 60% lung cancer in mice. 0.1 g/kg had 1/3 the effect and 0.6 g/kg had no extra effect. Another special oral extract 30 times less (0.01 g/kg) showed 50% reduction in lung cancer. A 3rd special extract of 99% ginsenoside Rg3 showed 65% less tumor volume. Another study in 3 colon cancers indicate injections of 50 mg/kg mice (0.3 g per 70kg person) of the extract from the berry of american ginseng had 65% smaller tumors and 100% survival. 20 mg/kg injections had very little effect (as with most of these, dose is everything). Ginsenoside Rg3 was the largest component of the American Berry but not root and root had no effect. The berries had to be steamed to get the Rg3 out and un-steamed had none of it and had almost no effect.

Genistein, Soy Phytochemical Concentrate 0.5% in diet (2.5 to 5 g/d) containing genistein reduced bladder metastasis to lung by 95% whereas only 70% for genistein by itself (0.2% diet, 1 to 2 g/d), so other compounds had effect. Both kept initial tumor sizes to 50% of controls. Genistein also effective in breast cancer even after inoculation at only 0.02% diet. This might be a problem because it usually contains daidzein isoflavone which made tumors significantly worse in one of the above studies. These isoflavones do not overlap with the other flavonids. I need to research this one more.

I3C (from broccoli) 1% in diet (30 pills) has large benefit in small cell lung cancer but 0.5% had little effect. Another study showed 70% prevention at 1.8%. Another study used only 0.15% diet in mice to prevent 43% and 83% reduction in tumor multiplicity and adenocarcinoma. This seems to have stronger evidence than many, especially for prevention of smoker's lung cancer, but it may have a strong effect on estrogen.

GLA 12 g/day, 40 pills, maybe no more effective than fish oil. Only a couple of mice studies.

Beta-sitosterol for prostate and breast cancers. 1% in diet used. Only 2 or 3 mice studies.

IP6 had 50% reduction in prostate tumor weight at 1% to 2% in drinking water in two studies and 5 fold decrease in skin cancer at 2% when started before inoculation. Has to be in pure form in drinking water, not bound to proteins. The max possibly needed of 20g per day would be $5 a day in powder form. Only 2 or 3 mice studies.

Others being studied but not available: triterpenes lupeol and betulinic acid, ginkolide B. from ginko, luteolin (broccoli-like plants)

Capers as a good food choice: are the best source of have quercetin and kaempferol (flavonols) with 300 mg/100g. They have been shown independently to have an effect on cancer, but I have not yet researched it well. These are also in green tea. Too much quercetin by itself (pills) may cause depression.

Converting doses from mice to human. 1% in diet and 1% in water for mice is 5 to 10 grams per day for a 2000 calorie person. Converting doses between animals is accurately based on comparing calories consumed because the ultimate goal is to get the same ratio of all compounds ingested. Larger animals use fewer calories per body weight, so they use fewer nutrients per body weight because the turnover in nutrients is slower. For example, the ratios of "RDAs" in mice (and other mammals) to calories consumed is close to the ratios in humans. Mice food is standardized to 4.7 gross kcal/gram, but their ability to digest is about 8% less (4.3 gross kcal/g), so 1% in their diet is 2000/4.3 = 4.7 grams per 2000 calories. It is difficult to compare human and mice food based strictly on the 1% by weight because there might be a lot of fiber in the mice food (fewer calories per weight), but the 1% by water might be good because the amount of water needed should be close to the number of calories consumed, if there has not been a lot of sweating. Someone exercising a lot will need more water and food so that they will get a higher dose of the nutrients when following this "percent calorie" method. In some studies, the mice had an exercise program and the lab might be cold so that they might be consuming twice the calories of other similar mice in other lab conditions, which means they will get twice the dose. Cancer grows faster with higher calorie intake, but not if the calories are being burned through exercise or keeping warm. So more exercise for a given amount of calories will give an effectively higher dose because fewer calories consumed will be the same dose, but the growth rate of the cancer will slow for a metabolic reason. The rest of this paragraph goes into more detail. Many sources indicate mice drink about 1 mL for every 1 g of food, which was also stated as an assumption in two research papers. A paper on caffeine and green tea explicitly mentioned 2.5 ml water and 2.5 g food per day were measured in the non-caffeine group. So 1% in drinking water is same as 1% in food, about 4.7 grams per 2000 calories. The maintenance food intake for a lab mouse is supposed to be 2.3 g/d according to one authoritative source, but 3 g/d is commonly quoted. Using the 2.5 g/d stated in one paper, 1% in diet by weight, 8% comparatively wasted food, and the FDA's "km" values for a 20 g mouse, I get 5.6 g/d for a 60 kg person, which is close to the calorie method above if the 60 kg person eats 2000 kcals/day. The km values were originally meant to be accurate based on assuming surface area determines heat loss and therefore calorie intake. Surface area is R^2 and volume is R^3, so a bigger mammal loses less heat through its surface, i.e. R^2/R^3 = R^(2/3). This simple heat-loss thinking was found in 1988 to be an underestimate of the dose required by larger animals, but the standard was not changed because it provides a margin of safety for toxic compounds that both the FDA and EPA are most often interested in: pharmaceuticals and toxins. But my purpose here is for optimum nutrition of very safe compounds. So they still use the 2/3 power law instead of the 3/4. The equation is: (human dose)/kg = (animal dose)/kg * [(human BW)/(animal BW)]^(PL-1) where PL is power law. FDA uses PL=2/3 to come up with km factors that are used in a simplified equation: mg/kg human = mg/kg animal * km animal / km human. The km table is at the bottom reference. FDA uses "3" for mice which could have a lot of rounding-off error, not to mention a lot of variation in mice sizes. The 4.7 g dose per 2000 calories reasoning I used above is supposed to be as good as gold, and so is the 3/4 PL. But the 3/4 PL gives 3.4 g/d for a 60 kg person, which would imply a 60 kg person consumes only 1,200 kcal/d if it was identical to the calorie or water methods I greatly prefer. I'll err on the side of the higher result of 4.7. All this is to show how carefully I've decided on 4.7 g/d per 2000 calories. The 4.7 g/d calorie method can be checked by comparing RDAs per calorie in humans and mice: about 1/3 of the human RDAs are 1.8 to 3 times as much per calorie, 1/3 are about the same, and 1/3 are half as much. So all seems good. One caveat: a lot of debate surrounds RDAs, and the methods and reasoning for determining RDAs in mice and humans might be very different. Conversely, mice and other mammal RDAs may have been inadvertently biased towards human RDAs and vice versa. But if RDAs are representative of other nutrients and if the RDA data for both species is accurate, giving a human TWICE the RDA dose per calorie of a mouse provides an 66% of the needs for 1/3 of the RDAs, twice as much as needed for 1/3, and 3 to 6 times more than needed for 1/3. Twice as much as 1% in the diet or water of a mouse (4.7 g/d per 2000 kcals) would be 9.4 g per 2000 calories. So this is how I get 5 to 10 g/d for a 2000 kcal diet as being equal to 1% by weight of food or 1% by volume of water in other mammals (not just mice because it is based on calorie consumption). I used mice as a starting point because they are the most commonly studied and should have the largest error because they are so small. Rats who weigh 15 times more than mice have much less variation when compared to humans, and the average of the ratio of RDAs to calories consumed remains the same. So when converting 1% nutrient in food and water in other mammals to humans, 5 g and 10 g per 2000 calories seem to be numbers that are "guessed to be adequate" and "probably adequate". For example, one study on caffeine indicates that either mice are very sensitive to caffeine or that my 4.7 g per 2000 calories equivalent to 1% in drinking water is to low because the mice drank 40% more water (probably caffeine-induced dehydration) and at 0.02% in water they were getting a dose equivalent to only 280 mg/d in 2000 kcal humans which is only 3 cups of coffee. The mice had 10% lower body weight and 50% fewer tumors. If this large benefit from caffeine occurs in humans, it would have to be a lot more than 3 cups of coffee, giving support for 10 g/d instead of 5 g/d per 2000 kcal diets for the conversion. If the higher dose is correct, people in clinical trials that are based on mouse data are often getting 4 times less than needed the dose because the FDA km method gives doses that are typically 25% too low and at least 1/3 of the RDA's (for example) need 3 times more in humans. This will result in 4 times "more cancer" than necessary in human trials for 1/3 of the nutrients being tested. Most of the nutrients above show a linear effect on cancer, so dose is everything. However, it seems that some trials are basing the dosages roughly on percent diet.

Links

fish oil, at least 60 ml/day, 6/month, $4.5/day
http://www.iherb.com/Carlson-Labs-The-Very-Finest-Fish-Oil-Lemon-Flavor-16-8-fl-oz-500-ml/2796?at=0

pomegranate, 4 pills/day, 4 bottles/month, $2/day
http://www.iherb.com/Life-Extension-Pomegranate-Extract-Capsules-30-Veggie-Caps/7453?at=0

green tea extract, 12 pills/day, 2 bottles/month, $1/day
http://www.iherb.com/Now-Foods-EGCg-Green-Tea-Extract-400-mg-180-Vcaps/11598?at=0

grape seed extract, 12 pills/day, 4 bottles/month, $2/day
http://www.iherb.com/Now-Foods-Grape-Seed-250-mg-90-Vcaps/7240?at=0

FDA km values
60 kg human 37
20 kg child 25
baboon 20
dog 20
monkey 12
rabbit 12
guinea pig 8
rat 6
hamster 5
mouse 3