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[A1CR]

Calorie Restriction's ability to prevent cancer is well documented (at least in animals). But how about once someone has cancer? Can CR be helpful, or is it ill-advised?

The following discussion by MR addresses the issue. The conclusion looks pretty favorable, especially for hormone-dependent cancers:

(1) reports that "manipulation of IGF-1 level through dietary intervention influences tumor growth and metastasis. ... [D]ownregulation of this pathway in vivo as a consequence of dietary restriction results in antitumorigenic activity." If we're talking about "tumor growth and metastasis", then this requires established tumors. (Indeed, any work on metastasis & CR -- which I'm not going to specifically check into at this time but which I know exists (others please chime in!))

(2) implanted " Two transplantable prostate tumor models, i.e., the androgen-dependent Dunning R3327-H adenocarcinoma in rats and the androgen-sensitive LNCaP human carcinoma" into "in severe combined immunodeficient mice" -- the equivalent of the 'bubble babies' -- " in ad libitum fed rats or in animals whose energy intake was restricted by 30% using three different methods, i.e., total diet restriction, carbohydrate restriction, or lipid restriction." "R3327-H tumors were smaller in energy-restricted or castrated rats than in control rats (P<.001). Tumors from energy-restricted rats exhibited changes in tumor architecture characterized by increased stroma and more homogeneous and smaller glands. In castrated rats, the tumor proliferation index was reduced (P<.0001), whereas apoptosis was increased in both energy-restricted (P<.001) and castrated (P<.001) rats. Tumor microvessel density and VEGF expression were reduced by energy restriction and castration (P<.003 versus control). Restriction of energy intake by reduction of carbohydrate intake, lipid intake, or total diet produced a similar inhibition of growth of R3327-H or LNCaP tumors."

The abstract of (3) is poorly-written, so one can't be SURE, but since their CONCLUSION is about "protection from the skin tumor-promoting effect of TPA", one presumes that the experiment was actually designed to TEST this, which would be done by first initiating a tumor & then promoting it, initiating CR AFTER initiation (& perhaps even after administering the promoting agent). What they SAY is that "stated intent is to test "A total of five groups of 14 male NMRI mice [whose T-cell maturation is severely impaired, NB] were initiated with ... (DMBA) and promoted twice weekly with ... (TPA). Food intake was ad libitum (all 3 TPA dose levels) or restricted to 70% (high and intermediate TPA dose levels)."

Anyway, the results: "The median latency time (t50) for the appearance of skin papilloma in the high-, intermediate-, and low-dose TPA groups fed ad libitum was 9, 15.5, and 23.5 weeks, respectively. The diet-restricted groups (high and intermediate TPA dose) showed t50 values of 16 and 26 weeks. Therefore, diet restriction to 70% had approximately the same protective effect as reducing the dose of TPA by a factor of two."

In (4), "Heterozygous p53-deficient mice received a bladder carcinogen, p-cresidine, to induce preneoplasia. After confirmation of bladder urothelial preneoplasia, the mice were divided into three groups: (a) ad libitum; (b) 20% DR; and (c) 20% DR plus IGF-I (IGF-I/DR). Serum IGF-I was lowered 24% by DR but was completely restored in the IGF-I/DR-treated mice ..."

" Although tumor progression was decreased by DR, restoration of IGF-I serum levels in DR-treated mice increased the stage of the cancers. Furthermore, IGF-I modulated tumor progression independent of changes in body weight. Rates of apoptosis in the preneoplastic lesions were 10 times higher in DR-treated mice compared to those in IGF/DR- and ad libitum-treated mice. Administration of IGF-I to DR-treated mice also stimulated cell proliferation 6-fold in hyperplastic foci. In conclusion, DR lowered IGF-I levels, thereby favoring apoptosis over cell proliferation and ultimately slowing tumor progression."

Now, (5) is at this point third-hand. The abstract isn't available on MEDLINE, but according to (5), it indicates that "The first tests of these intuitions in animal models were reported in 1909 by Moreschi and confirmed by Rous in 1914; both investigators demonstrated that calorie restriction (CR) ... inhibited the growth of transplanted tumors in mice".


-MR

1: Kari FW, Dunn SE, French JE, Barrett JC.
Roles for insulin-like growth factor-1 in mediating the anti-carcinogenic
effects of caloric restriction.
J Nutr Health Aging. 1999;3(2):92-101. Review.
PMID: 10885804 [PubMed - indexed for MEDLINE]

2: Mukherjee P, Sotnikov AV, Mangian HJ, Zhou JR, Visek WJ, Clinton SK.
Energy intake and prostate tumor growth, angiogenesis, and vascular endothelial growth factor expression.
J Natl Cancer Inst. 1999 Mar 17;91(6):512-23.
PMID: 10088621 [PubMed - indexed for MEDLINE]

3: Fischer WH, Lutz WK.
Influence of diet restriction and tumor promoter dose on cell proliferation, oxidative DNA damage and rate of papilloma appearance in the mouse skin after initiation with DMBA and promotion with TPA.
Toxicol Lett. 1998 Sep 1;98(1-2):59-69.
PMID: 9776562 [PubMed - indexed for MEDLINE]

4: Dunn SE, Kari FW, French J, Leininger JR, Travlos G, Wilson R,
Barrett JC.
Dietary restriction reduces insulin-like growth factor I levels, which
modulates apoptosis, cell proliferation, and tumor progression in p53-deficient mice.
Cancer Res. 1997 Nov 1;57(21):4667-72.
PMID: 9354418 [PubMed - indexed for MEDLINE]

5: Kritchevsky D.
Undernutrition and chronic disease: cancer.
Proc Nutr Soc. 1993 Feb;52(1):39-47. Review. No abstract available.
PMID: 8493275 [PubMed - indexed for MEDLINE]

6. Hursting SD, Lavigne JA, Berrigan D, Perkins SN, Barrett JC.
CALORIE RESTRICTION, AGING, AND CANCER PREVENTION: Mechanisms of Action and Applicability to Humans.
Annu Rev Med. 2003;54:131-52.
PMID: 12525670 [PubMed - in process]

7. Br J Cancer 2002 May 20;86(10):1615-21
Dietary restriction reduces angiogenesis and growth in an orthotopic mouse brain tumour model.
Mukherjee P, El-Abbadi MM, Kasperzyk JL, Ranes MK, Seyfried TN.
PMID: 12085212

[A1CR]

Here's a graphic that illustrates how cell mutations propagate into cancer:



Cancers are caused by a series of mutations. Each mutation alters the behavior of the cell somewhat