Flaxseed

Dietary flaxseed: preliminary evidencesignificant effects in small or poorly designed clinical studies OR conflicting results in adequate studies but a preponderance of evidence of an effect (this is the CancerChoices definition; other researchers and studies may define this differently) of anticancer action among people with breast cancer eating flaxseed

• Less tumor cell proliferation, lower markersa chemical or substance, such as certain proteins or genetic material, that are associated with the presence of cancer or a change in status or prognosis; these markers can be detected in blood, urine, or tissue. Tumor markers are not direct measures of clinical outcomes such as survival or metastasis, and if a therapy or treatment shows an impact only on tumor markers, we cannot surmise that it will affect survival. of cell growth, and higher cell death (apoptosis), among postmenopausal women with newly diagnosed breast cancer eating flaxseed compared to placeboa pill, medicine, or procedure—thought to be both harmless and ineffective—prescribed for the psychological benefit to the patient or as a sham treatment in a study to allow a comparison to a therapy of interest in a small RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects¹Thompson LU, Chen JM, Li T, Strasser-Weippl K, Goss PE. Dietary flaxseed alters tumor biological markers in postmenopausal breast cancer. Clinical Cancer Research. 2005 May 15;11(10):3828-35.

Modest evidencesignificant effects in at least three small but well-designed randomized controlled trials (RCTs), or one or more well-designed, mid-sized clinical studies of reasonably good quality (RCTs or observational studies), or several small studies aggregated into a meta-analysis (this is the CancerChoices definition; other researchers and studies may define this differently) of lower cancer proliferation among men with prostate cancer adding flaxseed to their diets

• 23% lower levels of a tumor biomarker among men with localized prostate cancer adding ground flaxseed to their diets for 30 days compared to controls in a mid-sized RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects²Azrad M, Vollmer RT et al. Flaxseed-derived enterolactone is inversely associated with tumor cell proliferation in men with localized prostate cancer. Journal of Medicinal Food. 2013 Apr;16(4):357-60.
• Lower proliferation rates but no change in cell death (apoptosis) or cancer biomarkersa chemical or substance, such as certain proteins or genetic material, that are associated with the presence of cancer or a change in status or prognosis; these markers can be detected in blood, urine, or tissue. Tumor markers are not direct measures of clinical outcomes such as survival or metastasis, and if a therapy or treatment shows an impact only on tumor markers, we cannot surmise that it will affect survival. before surgery among men with prostate cancer adding flaxseed to their diets compared to controls in a mid-sized RCT of moderate quality³Demark-Wahnefried W, Polascik TJ et al. Flaxseed supplementation (not dietary fat restriction) reduces prostate cancer proliferation rates in men presurgery. Cancer Epidemiology, Biomarkers & Prevention. 2008 Dec;17(12):3577-87.

Preliminary evidencesignificant effects in small or poorly designed clinical studies OR conflicting results in adequate studies but a preponderance of evidence of an effect (this is the CancerChoices definition; other researchers and studies may define this differently) of lower increase in blood supply to tumors before surgery among men with prostate cancer treated with flaxseed

• Lower markers of increased blood supply (angiogenesis) before surgery among men with prostate cancer treated with 30 g flaxseed daily for an average of 30 days compared to a normal diet in a mid-sized RCT⁴Heymach JV, Shackleford TJ et al. Effect of low-fat diets on plasma levels of NF-κB-regulated inflammatory cytokines and angiogenic factors in men with prostate cancer. Cancer Prevention Research. 2011 Oct;4(10):1590-8.

Flaxseed with a low-fat diet: preliminary evidencesignificant effects in small or poorly designed clinical studies OR conflicting results in adequate studies but a preponderance of evidence of an effect (this is the CancerChoices definition; other researchers and studies may define this differently) of slower prostate cancer growth among men combining dietary flaxseed with a low-fat diet

• Lower prostate-specific antigenprostate-specific antigen (PSA): a protein produced by both normal and malignant cells of the prostate gland; the blood level of PSA is often elevated in men with prostate cancer (PSA) and cell proliferation rates among men with nonspecific prostate epithelium growth eating a low-fat diet supplemented with 30g flaxseed a day for 6 months compared to baseline in a small uncontrolled triala study in which a therapy is used, but without a comparison group against which to judge outcomes; an uncontrolled trial is considered a weak study design⁵Demark-Wahnefried W, Robertson CN et al. Pilot study to explore effects of low-fat, flaxseed-supplemented diet on proliferation of benign prostatic epithelium and prostate-specific antigen. Urology. 2004 May;63(5):900-4.
• A weak trendan apparent change due to a therapy, close to but not achieving full statistical significance (this is the CancerChoices definition; other researchers and studies may define this differently toward decreased prostate-specific antigen (PSA) levels among men with less aggressive cancer but no evidence of an effect on PSA overall among men with prostate cancer awaiting prostatectomy eating a low-fat diet with 30 g supplemental flaxseed a day for an average of 34 days compared to baseline in a small uncontrolled trial⁶Demark-Wahnefried W, Price DT et al. Pilot study of dietary fat restriction and flaxseed supplementation in men with prostate cancer before surgery: exploring the effects on hormonal levels, prostate-specific antigen, and histopathologic features. Urology. 2001 Jul;58(1):47-52.
• Lower levels of a biomarkera chemical or substance, such as certain proteins or genetic material, that are associated with the presence of cancer or a change in status or prognosis; these markers can be detected in blood, urine, or tissue. Tumor markers are not direct measures of clinical outcomes such as survival or metastasis, and if a therapy or treatment shows an impact only on tumor markers, we cannot surmise that it will affect survival. associated with cell proliferation (MIB-1) among men with prostate cancer awaiting prostatectomy eating a low-fat diet with 30 g supplemental flaxseed a day for an average of 34 days compared to historical controls in a small controlled triala study design in which people are assigned to either an experimental group or a control group to compare the outcomes from different treatment; assignment is not random, and so this is not as strong a study design as a randomized controlled trial, but still stronger than an uncontrolled trial⁷Demark-Wahnefried W, Price DT et al. Pilot study of dietary fat restriction and flaxseed supplementation in men with prostate cancer before surgery: exploring the effects on hormonal levels, prostate-specific antigen, and histopathologic features. Urology. 2001 Jul;58(1):47-52.

Mistletoe, pharmacological ascorbate, probiotics, and several supplements, including a fiber supplement including flaxseed: weak evidenceone or more case studies, supported by animal evidence OR small treatment effects of limited clinical significance OR studies with no controls OR weak trends of effects (this is the CancerChoices definition; other researchers and studies may define this differently) of complete remission in a single person with high grade, non-muscle involved bladder cancer refractory to Bacillus Calmette-Guerin treated with intravenous pharmacological ascorbate and subcutaneous mistletoe along with several supplements

• Complete remission (no evidence of disease) in a case studya descriptive and exploratory analysis of a person, group, or event regarding changes observed over time; because changes due to treatment are not compared to similar changes over time without treatment, a case study is considered a weak study design of a nonsmoking woman with high grade, non-muscle involved bladder cancer (carcinoma in situ) refractory to Bacillus Calmette-Guerin treated with intravenous pharmacological ascorbate and subcutaneous mistletoe 3 times a week, and also intravenous and intravesical mistletoe once a week for an 8-week induction treatment using a dose-escalation protocol and then maintenance therapy of the same protocol for 3 weeks every 3 months for 2 years; plus these supplements:⁸Davis D, Seely D et al. Complete remission of BCG-refractory high-grade bladder CIS with pharmacologic ascorbate and mistletoe. Alternative Therapies in Health and Medicine. 2023 May;29(4):6-17.
  • Daily: turmeric, vitamin D, omega-3 fatty acids, coenzyme Q10, chaga mushroom, and melatonin at night
  • During induction: probiotics
  • During maintenance: probiotics, melatonin 4 times a day, and a fiber supplement made of flaxseed, probiotics, and L-glutamine

Flax oil with intravenous vitamin C and other supplements and medications: weak evidence of good health and wellness with no symptoms of metastasis or recurrence 9 years after diagnosis in a person with bladder cancer treated with intravenous vitamin C, flax oil, and other supplements

• Good health with no symptoms of metastasis or recurrence 9 years after diagnosis in a man with a primary bladder tumor treated with 30 g intravenous vitamin C twice per week for 3 months, followed by 30 g once every 1–2 months for 4 years, along with botanical extract, chondroitin sulfate, chromium picolinate, flax oil, glucosamine sulfate, α-lipoic acid, Lactobacillus acidophilus, L. rhamnosus and selenium in a case study⁹Padayatty SJ, Riordan HD et al. Intravenously administered vitamin C as cancer therapy: three cases. Canadian Medical Association Journal. 2006;174(7):937-42.

Preliminary evidencesignificant effects in small or poorly designed clinical studies OR conflicting results in adequate studies but a preponderance of evidence of an effect (this is the CancerChoices definition; other researchers and studies may define this differently) of lower body weight among women with polycystic ovary syndrome (PCOS) treated with flaxseed powder

• Lower body weight among women with polycystic ovary syndrome (PCOS) treated with 30 g flaxseed powder daily and lifestyle modification such as dietary pattern, exercise, and behavioral therapies compared to lifestyle modification alone in a small RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects¹⁰Haidari F, Banaei-Jahromi N et al. The effects of flaxseed supplementation on metabolic status in women with polycystic ovary syndrome: a randomized open-labeled controlled clinical trial. Nutrition Journal. 2020 Jan 24;19(1):8.

Dietary flaxseed: strong evidenceconsistent, significant effects in several large (or at least one very large) well designed clinical studies or at least two meta-analyses of clinical studies of moderate or better quality (or one large meta-analysis) finding similar results (this is the CancerChoices definition; other researchers and studies may define this differently) of better markers of blood sugar and insulin sensitivity among people adding flaxseed to their diets

• Lower insulin resistancea condition in which cells in your muscles, fat, and liver don’t respond well to insulin and can’t efficiently take up glucose from your blood for energy among women with polycystic ovary syndrome (PCOS) treated with 30 g flaxseed powder daily and lifestyle modification such as dietary pattern, exercise, and behavioral therapies compared to lifestyle modification alone in a small RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects¹¹Haidari F, Banaei-Jahromi N et al. The effects of flaxseed supplementation on metabolic status in women with polycystic ovary syndrome: a randomized open-labeled controlled clinical trial. Nutrition Journal. 2020 Jan 24;19(1):8.
• Better blood sugar control and insulin levels and sensitivity among people eating whole flaxseed for 12 weeks or more in a meta-analysisa statistical analysis that combines the results of two or more research studies; the results of smaller research studies addressing the same or similar questions can be analyzed as though they are one bigger, more powerful study of 12 RCTs¹²Mohammadi-Sartang M, Sohrabi Z, Barati-Boldaji R, Raeisi-Dehkordi H, Mazloom Z. Flaxseed supplementation on glucose control and insulin sensitivity: a systematic review and meta-analysis of 25 randomized, placebo-controlled trials. Nutrition Reviews. 2018 Feb 1;76(2):125-13.
• Better peak blood glucose levels among healthy people after eating flax bread compared to white bread in a small RCT¹³Dahl WJ, Lockert EA, Cammer AL, Whiting SJ. Effects of flax fiber on laxation and glycemic response in healthy volunteers. Journal of Medicinal Food. Winter 2005;8(4):508-11.

Flaxseed supplements: no evidence of an effectoverall, one or more studies did not demonstrate that a treatment or intervention led to an expected outcome; this does not always mean that there is no effect in clinical practice, but that the studies may have been underpowered (too few participants) or poorly designed. Larger, well-designed studies provide more confidence in making assessments. on blood sugar or insulin sensitivity among people using flaxseed oil and lignan extract in a combined analysis of studies

• No evidence of an effect on blood sugar control or insulin levels and sensitivity among people treated with flaxseed oil and lignan extract compared to controls in a meta-analysis of 12 RCTs¹⁴Mohammadi-Sartang M, Sohrabi Z, Barati-Boldaji R, Raeisi-Dehkordi H, Mazloom Z. Flaxseed supplementation on glucose control and insulin sensitivity: a systematic review and meta-analysis of 25 randomized, placebo-controlled trials. Nutrition Reviews. 2018 Feb 1;76(2):125-13.

Sex hormones

Preliminary evidencesignificant effects in small or poorly designed clinical studies OR conflicting results in adequate studies but a preponderance of evidence of an effect (this is the CancerChoices definition; other researchers and studies may define this differently) of sex hormone changes among postmenopausal women eating dietary flaxseed

• Higher 2-hydroxyestrone level and 2:16α-hydroxyestrone ratio among postmenopausal women eating 15 g ground flaxseed daily for 7 weeks in a small RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects;¹⁵Chang VC, Cotterchio M et al. Effect of dietary flaxseed intake on circulating sex hormone levels among postmenopausal women: a randomized controlled intervention trial. Nutrition and Cancer. 2019;71(3):385-398. a higher ratio of 2-hydroxyestrone/16-hydroxyestrone may be associated with lower long-term risk for breast cancer in women with risk factors for breast cancer as well as other estrogen-sensitive diseases such as cervical cancer and osteoporosis¹⁶Marchand LR, Stewart JA. 2-Hydroxyestrone/16-Hydroxyestrone Ratio. In Rakel D (editor). Integrative Medicine (Fourth Edition), Chapter 78—Breast Cancer. Elsevier. 2018;772-784.e7; Im A, Vogel VG et al. Urinary estrogen metabolites in women at high risk for breast cancer. Carcinogenesis. 2009 Sep;30(9):1532-5.

Preliminary evidence of lower levels of some sex hormones among obese postmenopausal women without cancer eating dietary flax, but weak evidenceone or more case studies, supported by animal evidence OR small treatment effects of limited clinical significance OR studies with no controls OR weak trends of effects (this is the CancerChoices definition; other researchers and studies may define this differently) among women who are not obese.

• Lower testosterone and estrone among obese postmenopausal women (not specific to cancer) and a weak trendan apparent change due to a therapy, close to but not achieving full statistical significance (this is the CancerChoices definition; other researchers and studies may define this differently toward lower levels of estradiol, estrone, and testosterone among non-obese postmenopausal women without cancer eating ground flaxseeds compared to baseline in a small observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods study ¹⁷Sturgeon SR, Heersink JL et al. Effect of dietary flaxseed on serum levels of estrogens and androgens in postmenopausal women. Nutrition and Cancer. 2008;60(5):612-8.

Other hormones

Preliminary evidence of lower leptin levels—a hormone that helps regulate energy balance by inhibiting hunger—among women with polycystic ovary syndrome (PCOS) treated with flaxseed powder

• Lower leptin levels among women with polycystic ovary syndrome (PCOS) treated with 30 g flaxseed powder daily and lifestyle modification such as dietary pattern, exercise, and behavioral therapies compared to lifestyle modification alone in a small RCT¹⁸Haidari F, Banaei-Jahromi N et al. The effects of flaxseed supplementation on metabolic status in women with polycystic ovary syndrome: a randomized open-labeled controlled clinical trial. Nutrition Journal. 2020 Jan 24;19(1):8.

No evidence of an effectoverall, one or more studies did not demonstrate that a treatment or intervention led to an expected outcome; this does not always mean that there is no effect in clinical practice, but that the studies may have been underpowered (too few participants) or poorly designed. Larger, well-designed studies provide more confidence in making assessments. on immune function among people adding flaxseed to their diets in one study

• An increase in one marker of immune response (IL-8) but no evidence of an effect on other inflammatory cytokines before surgery among men with prostate cancer treated with 30 g flaxseed daily for an average of 30 days compared to a normal diet in a mid-sized RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects¹⁹Heymach JV, Shackleford TJ et al. Effect of low-fat diets on plasma levels of NF-κB-regulated inflammatory cytokines and angiogenic factors in men with prostate cancer. Cancer Prevention Research. 2011 Oct;4(10):1590-8.

Dietary flaxseed with a low-fat diet: weak evidenceone or more case studies, supported by animal evidence OR small treatment effects of limited clinical significance OR studies with no controls OR weak trends of effects (this is the CancerChoices definition; other researchers and studies may define this differently) of lower levels of testosterone and free androgen index among men with prostate cancer awaiting prostatectomy and treated with supplemental flaxseed; higher levels of these hormones are linked to mortality or risk of progression among people with advanced prostate cancer²⁰Claps M, Petrelli F et al. Testosterone levels and prostate cancer prognosis: systematic review and meta-analysis. Clinical Genitourinary Cancer. 2018 Jun;16(3):165-175.e2.

• Lower levels of testosterone and free androgen index in 25 men with prostate cancer awaiting prostatectomy and following a low-fat diet with 30 g supplemental flaxseed a day for an average of 34 days compared to baseline in a small uncontrolled triala study in which a therapy is used, but without a comparison group against which to judge outcomes; an uncontrolled trial is considered a weak study design²¹Demark-Wahnefried W, Price DT et al. Pilot study of dietary fat restriction and flaxseed supplementation in men with prostate cancer before surgery: exploring the effects on hormonal levels, prostate-specific antigen, and histopathologic features. Urology. 2001 Jul;58(1):47-52.