| Scientific References for Dr.
Budwig's Research
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Research Studies On Animals & Humans Into the Effects of Flaxseed and Flaxseed Components (Lignan, Lignan Precursors & Oil) on Cancer and Tumor Growth
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| A 2002 animal experiment on the ”[e]ffect of flaxseed supplementation on prostatic carcinoma in transgenic mice” found that a ”diet supplemented with 5% flaxseed inhibits the growth and development of prostate cancer in the TRAMP model”. | |
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Aiming
to ”investigate the effects of flaxseed supplementation on
prostatic neoplasia in the transgenic adenocarcinoma mouse
prostate (TRAMP) model”, a ”total of 135 male TRAMP mice
5 to 6 weeks old were randomized to a control group (AIN-76A
diet) or an experimental group (AIN-76A diet plus 5%
flaxseed by weight). One half of the mice in each group were
treated for 20 weeks and the remainder for 30 weeks. At
autopsy, urogenital tissues (four prostatic lobes, seminal
vesicles, and emptied bladder), lungs, lymph nodes, and
grossly abnormal tissues were collected for histologic
evaluation. RESULTS: Of the control mice, 100% developed
prostate cancer versus 97% of the mice in the flaxseed
group. The tumor/urogenital weight was 3.6 +/- 0.4 g in the
controls versus 1.9 +/- 0.2 g in the flaxseed-treated mice
(P = 0.0005). At 20 weeks, no significant difference in
tumor grade was seen between the two groups; however, at 30
weeks, the flaxseed-treated mice had significantly less
aggressive tumors than did the controls (P = 0.01). The
prevalence of lung and lymph node metastases was 13% and
16%, respectively, in the control mice versus 5% and 12%,
respectively, in the experimental group (difference not
significant). After 20 weeks of treatment, cellular
proliferation (Ki-67) differed significantly between the
control and experimental groups (38.1 +/- 2.03 versus 26.2
+/- 2.03; P <0.0001), and the apoptotic index (deoxynucleotidyl
transferase-mediated dUTP-digoxigenin nick end labeling) was
1.45 +/- 0.14 versus 3.3 +/- 0.31 (P <0.0001). Similar
differences were seen after 30 weeks of treatment.
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| Dietary
flaxseed inhibits human breast cancer growth and metastasis
and downregulates expression of insulin-like growth factor and
epidermal growth factor receptor. Chen J, Stavro PM, Thompson LU. Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON, Canada M5S 3E2. |
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Recent studies indicate that diets rich in phytoestrogens and n-3 fatty acid have anticancer potential. This study determined the effect of flaxseed (FS), the richest source of lignans and alpha-linolenic acid, on growth and metastasis of established human breast cancer in a nude mice model. Estrogen receptor-negative human breast cancer cells, MDA-MB-435, were injected into the mammary fat pad of mice (Ncr nu/nu) fed a basal diet (BD). At Week 8, mice were randomized into two diet groups, such that the groups had similar tumor size and body weight. One continued on the BD, while the other was changed to BD supplemented with 10% FS, until sacrifice at Week 15. A significant reduction (P < 0.05) in tumor growth rate and a 45% reduction (P = 0.08) in total incidence of metastasis were observed in the FS group. Lung metastasis incidence was 55.6% in the BD group and 22.2% in the FS group, while the lymph node metastasis incidence was 88.9% in the BD group and 33.3% in the FS group (P < 0.05). Mean tumor number (tumor load) of total and lymph node metastasis was significantly lower in the FS than in the BD group (P < 0.05). Metastatic lung tumor number was reduced by 82%, and a significantly lower tumor trend (P < 0.01) was observed in the FS group. Lung weight, which also reflects metastatic tumor load, in the FS group was reduced by 20% (P < 0.05) compared with the BD group. Immunohistochemical study showed that Ki-67 labeling index and expression of insulin-like growth factor I and epithelial growth factor receptor in the primary tumor were lower in the FS (P < 0.05) than in the BD group.
In conclusion, flaxseed inhibited the established human breast
cancer growth and metastasis in a nude mice model, and this
effect is partly due to its downregulation of insulin-like
growth factor I and epidermal growth factor receptor
expression.
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| Flaxseed and its lignan and oil components reduce mammary tumor growth at a late stage of carcinogenesis. Thompson LU, Rickard SE, Orcheson LJ, Seidl MM. Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Ontario, Canada. | |
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Flaxseed, a rich source of mammalian lignan precursor
secoisolariciresinol- diglycoside (S.D.) and alpha-linolenic
acid (ALA), has been shown to be protective at the early
promotion stage of carcinogenesis. The objective of this study
was to determine whether supplementation with flaxseed, its
lignan or oil fractions, beginning 13 weeks after carcinogen
administration, would reduce the size of established mammary
tumors (present at the start of treatment) and appearance of
new tumors in rats. Dietary groups consisted of the basal diet
(BD, 20% corn oil) alone or supplemented with a gavage of 2200
nmol/day S.D. [S.D., equal to level in 5% flaxseed (F)], 1.82%
flaxseed oil (OIL, equal to level in 5% F) or 2.5% or 5%
flaxseed (2.5% F and 5% F, respectively).
After 7 weeks of
treatment, established tumor volume was over 50% smaller in
all treatment groups (OIL, 2.5% F, 5% F, P < 0.04; S.D., P
< 0.08) while there was no change in the BD group. New
tumor number and volume were lowest in the S.D. (P < 0.02)
and 2.5% F (P < 0.07) groups. The combined established and
new tumor volumes were smaller for the S.D., 2.5% F and 5% F
groups (P < 0.02) compared to the OIL and BD groups. The
high negative correlation (r = -0.997, P < 0.001) between
established tumor volume and urinary mammalian lignan
excretion in the BD, S.D., 2.5% F and 5% F groups indicates
that the reduction in tumor size is due in part to the lignans
derived from the S.D. in flaxseed. However, there was no
relationship between new or total tumor development and
urinary lignan levels. The effect of flaxseed oil may be
related to its high ALA content. In conclusion, the S.D. in
flaxseed appears to be beneficial throughout the promotional
phase of carcinogenesis whereas the oil component is more
effective at the stage when tumors have already been
established.
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| Flaxseed supplementation and early markers of colon carcinogenesis. Serraino M, Thompson LU. Department of Nutritional Sciences, University of Toronto, Ontario, Canada. | |
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Since flaxseed ingestion produces potentially anticarcinogenic
lignans in the colon, this study determined whether flaxseed
decreases the risk for colon carcinogenesis. Following a
single injection of azoxymethane (15 mg/kg body wt.), five
groups of male Sprague-Dawley rats were fed a high-fat (20%
corn oil) basal diet with or without supplementation with 5%
or 10% flaxseed meal (FM) or flaxseed flour (FF) for four
weeks. Upon sacrifice, colons were examined for aberrant
morphology and cell proliferation. In the descending colon of
supplemented groups, the total number of aberrant crypts and
foci were significantly reduced by 41-53% and 48-57%,
respectively. The labeling index (LI) was also 10-22% lower in
these groups, except for the 5% FM group. While these effects
are not linearly related to the level of flaxseed fed, it
suggests that flaxseed feeding may reduce the risk for colon
carcinogenesis. The original NCBI report with references
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| The
effect of flaxseed supplementation on early risk markers for
mammary carcinogenesis. Serraino M, Thompson LU. Department of Nutritional Sciences, University of Toronto, Ontario, Canada. |
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Since lignans have been suggested to have some
cancer-protective effects, flaxseed, the most abundant source
of lignan precursors, was tested for its effect on early
markers of risk for mammary carcinogenesis. Supplementation of
a high-fat diet with flaxseed flour (FF) or defatted flaxseed
meal (FM) (5% or 10%) reduced the epithelial cell
proliferation by 38.8-55.4% and nuclear aberrations by
58.8-65.9% in female rat mammary gland, with optimum effects
seen with the 5% FF. These protective effects were accompanied by increases in urinary lignan excretion indicating that they may be related to the ability of flaxseed to provide lignan precursors. The original NCBI report with references
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| Antitumorigenic effect of a mammalian lignan precursor from flaxseed. Thompson LU, Seidl MM, Rickard SE, Orcheson LJ, Fong HH. Department of Nutritional Science, Faculty of Medicine, University of Toronto, Ont, Canada. | |
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Secoisolariciresinol diglycoside (SD), a mammalian lignan
precursor found in high-fiber foods, was isolated from
flaxseed and tested for effects on mammary tumorigenesis in
rats fed a high-fat (20%) diet. Ingestion of purified SD at
1.5 mg/day for 20 weeks starting 1 week after treatment with
the carcinogen dimethylbenzanthracene resulted in a 37%
reduction (p < 0.05) in the number of tumors per
tumor-bearing rat and a 46% reduction (p < 0.05) in the
number of tumors per tumor-bearing rat and a 46% reduction
(p < 0.05) in the number of tumors per number of rats in
each group. Urinary mammalian lignan excretion significantly
increased (p < 0.0001) with SD treatment, indicating the
conversion of SD to mammalian lignans. No enlargement or
gross abnormalities of the major organs were observed in the
SD-treated rats. This study showed, for the first time, that
SD has an antitumor effect when provided at the early
promotion stage of tumorigenesis and may contribute to the
health benefits of high-fiber foods. The original NCBI report with references
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| Suppression of tumor growth and metastasis by dietary fish oil combined with vitamins E and C and cisplatin. Yam D, Peled A, Shinitzky M. Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot, Israel. | |
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The anticancer activity of omega-3 polyunsaturated fatty
acids (omega-3 PUFA) has been shown in a large number of
studies. This study was undertaken to analyze the combined
effect of omega-3 PUFA and antioxidative vitamins on the
level of spontaneous metastatic dissemination. The
supportive effect of this dietary combination on
chemotherapy with cisplatin (CP) was determined in parallel. METHODS: C57BL/6J mice bearing the Lewis lung carcinoma 3LL were fed ad libitum one of three isocaloric diets containing 5% soybean oil supplemented with 40 mg/kg alpha-tocopherol acetate (SO diet), or 4% fish oil plus 1% corn oil, and basal amounts of vitamin E (FO diet) or FO diet supplemented with vitamins E and C (FO+E+C diet). These diets were tested in combination with the conventional cytotoxic agent CP in a series of regimens. Tumor growth, feed consumption, body weight, lung metastasis and lung histology were followed. RESULTS: Both the FO dietary groups showed significantly lower tumor development than the SO group in all examined parameters, indicating that omega-3 PUFA have anticancer activity. However, the FO diet, in comparison with the FO+E+C diet induced a significantly slower rate of tumor growth, and lower metastatic load, as reflected in lung weight. The decrease in the anticancer activity of FO by the addition of vitamins E and C suggests that in situ oxidation of omega-3 PUFA underlies their anticancer action. It is thus proposed that oxidized omega-3 PUFA accumulates in the membranes and the cytosol of tumor cells, reducing their vitality and eventually leading to their death. No signs of anorexia or cachexia were observed in either FO group, in contrast to the SO group. CP treatment with the SO diet had no apparent therapeutic effect, while with the FO diets it reduced the metastatic load. The best regimen of this combined treatment was FO diet followed by CP treatment with FO diet supplemented with vitamins E and C after resection of the primary growth. This regimen could be translated to a combined therapy for human cancer. CONCLUSIONS: Diets enriched with omega-3 PUFA may have beneficial anticancer effects in particular when containing only basal amounts of antioxidants such as vitamin E or C. Furthermore, the addition of drugs which promote oxidation of omega-3 PUFA, such as ferrous salts (e.g. as prescribed for the treatment of anemia), may further increase these effects. However, the supportive effect of omega-3 PUFA in chemotherapy (e.g. with CP) increases when vitamins E and C are also included. The original NCBI report with references
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| Dietary
flaxseed inhibits human breast cancer growth and metastasis
and downregulates expression of insulin-like growth factor
and epidermal growth factor receptor. Chen J, Stavro PM, Thompson LU., Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON, Canada M5S 3E2. |
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Recent studies indicate that diets rich in phytoestrogens and n-3 fatty acid have anticancer potential. This study determined the effect of flaxseed (FS), the richest source of lignans and alpha-linolenic acid, on growth and metastasis of established human breast cancer in a nude mice model. Estrogen receptor-negative human breast cancer cells, MDA-MB-435, were injected into the mammary fat pad of mice (Ncr nu/nu) fed a basal diet (BD). At Week 8, mice were randomized into two diet groups, such that the groups had similar tumor size and body weight. One continued on the BD, while the other was changed to BD supplemented with 10% FS, until sacrifice at Week 15. A significant reduction (P < 0.05) in tumor growth rate and a 45% reduction (P = 0.08) in total incidence of metastasis were observed in the FS group. Lung metastasis incidence was 55.6% in the BD group and 22.2% in the FS group, while the lymph node metastasis incidence was 88.9% in the BD group and 33.3% in the FS group (P < 0.05). Mean tumor number (tumor load) of total and lymph node metastasis was significantly lower in the FS than in the BD group (P < 0.05). Metastatic lung tumor number was reduced by 82%, and a significantly lower tumor trend (P < 0.01) was observed in the FS group. Lung weight, which also reflects metastatic tumor load, in the FS group was reduced by 20% (P < 0.05) compared with the BD group.
Immunohistochemical study showed that Ki-67 labeling index
and expression of insulin-like growth factor I and
epithelial growth factor receptor in the primary tumor were
lower in the FS (P < 0.05) than in the BD group. In
conclusion, flaxseed inhibited the established human breast
cancer growth and metastasis in a nude mice model, and this
effect is partly due to its downregulation of insulin-like
growth factor I and epidermal growth factor receptor
expression.
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| Flaxseed inhibits metastasis and decreases extracellular vascular endothelial growth factor in human breast cancer xenografts. Dabrosin C, Chen J, Wang L, Thompson LU., Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, 150 College Street, ON, M5S 3E2, Toronto, Canada. | |
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Angiogenesis is important in
tumor growth, progression and metastatic dissemination. Vascular
endothelial growth factor (VEGF) is one key factor in promotion of
breast cancer angiogenesis. VEGFs are bioactive in the extracellular
space where they become available to the endothelial cells.
Phytoestrogens such as lignans have been shown to alter breast cancer
incidence and be cancer-protective in rats. We show that supplementation
of 10% flaxseed, the richest source of mammalian lignans, to nude mice
with established human breast tumors reduced tumor growth and
metastasis. Moreover, flaxseed decreased extracellular levels of VEGF,
which may be one mechanistic explanation to the decreased tumor growth
and metastasis.
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