Dietary supplements and functional foods

Question 1

Aloe (aloe barbadensis miller)

Answer 1

cactus like plant, primary form is a gel or juice

may be useful for constipation

well tolerated and good safety data on juice and gel, aloe latex orally may be unsafe and cause diarrhea

• may delay radiation dermatitis in patients with H&N cancer
• in RCT, patients with lung cancer who consumed aloe mixed with honey TID during chemo had significantly increases response compared to control
• radiation proctitis significantly improved in patients who used aloe vera 3% ointment in a pre-lim RCT

Question 2

alpha- lipoic acid

Answer 2

cellular antioxidant important for energy production that is naturally synthesized

reported benefits: may improve insulin sensitivity and DM management, aid with HTN, mitigate radiation damage, reduce symptoms of neurotoxicity, inhibit growth of breast, colon, lung, liver and pancreatic cancer cells

generally, very well tolerated

Evidence:

• does seem to help with BG levels and insulin sensitivity
• inhibits tumor cells in in vitro and in vivo studies
• ineffective at preventing neurotoxicity
• reduces neuropathic symptoms and TG and QOL

Dietary sources: spinach, broccoli and brewer’s yeast

Question 3

Black Cohosh (cimicifuga racemosa)

Answer 3

the rhizome and roots of this plant are used in herbal tx. Remifemin (Nature’s Way), a commercial preparation provides 10 g of the root or rhizome per tablet

Claims: suppresses symptoms associated with menopause (hot flashes) and cancer tx.

Possibly unsafe during pregnancy and lactation. Potential liver toxicity. Mild adverse events include headaches, vomiting and GI irritation

Evidence:

• insufficient evidence to recommend during cancer tx.
• some mixed evidence to support claims but may interfere with meds

Can interact with tamoxifen, atorvastatin, azathioprine, cyclosporine and increase the toxic effects of doxorubicin and docetaxel

Question 4

Coenzyme Q10 (CoQ10)

Answer 4

fat soluble bioactive substance is found in every cell in the body

Claims: endogenous antioxidant involved in cellular energy productions, may reduce renal toxicity of doxorubicin (Adriamycin)

Concerns: structurally similar to menaquinone (vit K2) and may have procoagulant effects. Mild GI symptoms have been reported.

Evidence:

• may reduce toxicity of some chemos but there is insufficient evidence to recommend.
• may help prevent cardiotoxic and nephrotoxicity of doxorubicin and carboplatin
• supplement with 300 mg/d of CoQ10 may increase antioxidant levels and reduce the oxidative stress and inflammation levels in patients with HCC after surgery

contraindicated in patients taking warfarin, concern that since it’s an antioxidant it could interfere with chemos

Question 5

Curcumin (curcuma longa)

Answer 5

naturally occuring polyphenol in tumeric, derived from plant’s rhizomes and believed to be the active component of tumeric spice

claims: may inhibit growth of cancer cells, antioxidant, anti-inflammatory, and has anti-cancer properties
Concerns: may prolong activated partial thromboplastin time and prothrombin time

evidence:
- mixed evidence for a variety of claims but generally positive
- insufficient evidence to make a recommendation to use it
- curcumin is known to have poor solubility and low bioavailability
- some supplements combine it with piperine (a spice in black pepper) to increase absorption, but this can interfere with phenytoin, propranolol, and theophylline
- incorporating tumeric within a varied diet is reasonable and safe

Question 6

3,3-Diindolylmethane (DIM) and indole-3- carbinol (I3C)

Answer 6

DIM is naturally occurring plant alkaloid bioactive metabolite of I3C found in cruciferous veg such as broccoli, cauli, brussels sprouts, cabbage, kale, kohlrabi, bok choy, mustard greens and turnips

Claims: chemoprevention activity in breast and squam lung cancer, affects multiple signaling pathways and target molecules controlling cell division, apoptosis, or angiogenesis deregulated in cancer cells.

Concerns: DIM may interfere with hormone therapy due to potential antiestrogenic effects

Evidence:

• well tolerated
• some evidence to support claims
• enhances therapeutic efficacy of paclitaxel in gastric cancer

Question 7

Garlic (allium sativum)

Answer 7

perennial bulb, known for it’s allium compounds, often used as a flavor enhancer

claims: may stimulate apoptosis and help regulate cell cycles
concerns: may interfere with the function of some prescription drugs including saquinavir and antiplatelet medications

Evidence:

• shows potential as anticancer tx, however current evidence is insufficient to make that recommendation
• allyl sulfides which make up 94% of compounds in garlic may promote apoptosis and cell arrest and inhibit growth of tumor cells
• associated with lower risk for gastric cancer
• one meta-analysis and the VITAL study found garlic supps increased colorectal cancer cancer risk

Question 8

Ginger (zingiber officinale)

Answer 8

Gingerols are major bioactive component in fresh ginger whereas shogaols (6-shogaol) are most abundant in dried ginger. Ginger is available in many forms

reported benefits: helps with heartburn, N, anorexia, D and gas, may inhibit carcinogenesis, has antioxidant and anti-inflammatory properties

Concerns: could interfere with anticoagulants

Evidence: promotes apoptosis and inhibits vascular endothelial growth factor (VEGF) expression.
Some evidence that it does help with nausea. Some evidence that it helps inhibit colorectal, hepatocellular, and prostate cancers

• current evidence insufficient to recommend as an antiemetic. No agreed upon dosage. GRAS up to 1000 mg/d (1 tsp fresh grated ginger extract, 2 mL liquid ginger extract, 4 cups prepackaged ginger tea, 2 tsp ginger syrup or 2 pieces crystallized ginger

Question 9

Ginkgo Biloba

Answer 9

Seeds and leaves of G. biloba are a source of bioactive compunds including triterpene, lactones, and flavonoids

reported benefits: may inhibit proliferation of cancer cells
concerns: may increase bleeding risk but evidence is inconclusive

Evidence:

• lots of rat and small studies.
• may reduce toxicity of Cisplatin
• current evidence is insufficient, but promising
• may interfere with anticoagulants and antiseizure meds
• discourage with alkylating agents, antitumor antibiotics, and platinum analogues b/c of scavanging free radical effects

Question 10

Glutamine

Answer 10

most abundant non-essential AA in the body, involved in rapid cell turnover like in the GI mucosa and immune system

reported benefits: may reduce the inflammatory s/e of tx (diarrhea, mucositis, stomatitis, esophagitis), May play a role in maintaining the intestinal mucosal barrier

concerns: converted to ammonia and may decrease effectiveness of lactulose. May interact with seizure meds

Evidence: some evidence although not unequivocal and should be evaluated by medical team with consideration of contraindications

• decent evidence to support usage for mucositis
• well tolerated and associated with improvements in sensory function and QOL
• depleted with stress, such as major surgery, sepsis and cancer

Question 11

Green Tea (camellia sinensis)

Answer 11

Main extracts are polyphenols (composed of catechins) and main polyphenol is EGCG (epigallocatechin-3-gallate)

reported benefits: hepato-, cardio, neuro-protective, anti- cancer, obesity, diabetic, bacterial, viral and hypoglycemic effects
Concerns: could theoretically interact with antiplatelet drugs, caffeine issues (insomnia, restlessness, heart irregularities, etc), could inhibit several drug metabolizing enzymes but not proven in humans.

Evidence:

• EGCG shown to inhibit tumorigenesis in animal models for tons of solids cancers
• may inhibit cytochrome P450 isozymes (discourage us with erlotinnib/ Tarceva and Pazopanib/ votrient)
• hepatotoxicity and GI disturbances are harsh side effects in multiple tests
• impossible to get to damaging levels of EGCG with normal tea consumption

Question 12

Melatonin

Answer 12

natural indolamine produced by the pineal gland that has many functions including circadian rhythm regulation.

reported benefits: anticancer effects for multiple cancers, possibly including antiproliferative and proapoptotic effects

Concerns: may be unsafe to use in pregnancy, could increase risk of bleeding by increasing anticoagulant effects of herbs

Evidence:

• several prospective studies showed inverse correlation between melatonin metabolites and the risk of breast cancer, disrupts estrogen dependent cell signaling
• enhanced aromatase expression and increased adiponectin secretion in women
• increased sensitivity/ enhanced effects of multiple chemos
• generally safe and well tolerated
• 1-5 mg/d for sleep, but up to 20 mg/d for anticancer effects

Question 13

N- acetylcysteine (NAC)

Answer 13

antioxidant that contains thiol groups, stimulates glutathione synthesis and scavenges free radicals

Reported benefits: has antioxidant properties, prevents nuclear factor kappaB activation which increases inflammatory response, used in EDs as a mucolytic and antidote for ODs
Concerns: none

Evidence:

• improves the utility of chemos by increasing cytotoxic effect while minimizing toxicity to host tissues- shown to be protective with cisplatin, 5-FU, cyclophosphamide, ifosfamide, MTX, oxaliplatin, doxil, and combined carbo, melphalan and etoposide phosphate
• generally well tolerated and has a very safe profile with minimal effects
• dosages range from 600- 1800 mg/d
• most side effects from NAC happened when taking >9 g/d in single doses

Question 14

Omega 3 fatty acids - ecosapentaenoic acid (EPA) and docosahexaenoicacid (DHA)

Answer 14

long chain FA found in fatty fish and supplements.

reported benefits: offers cardioprotective, anti-inflammatory, immunomodulatory effects, may reduce inflammation
concerns: EPA and DHA can increase bleeding risk if taking <4 g daily

Evidence: - may influence genes that modulate inflammation
-may increase apoptosis in preclinical trials
- a RCT with blinds and placebo demonstrated decreased risk of peripheral neuropathy from paclitaxel
- could reduce severity of mucositis
- up to 3 g/d considered safe, 4 g if monitored by a physician
-

Question 15

Quercetin

Answer 15

flavonoid found in a variety of foods including citrus, apples, onions, parsley, and tea, sold as a dietary supplement
reported benefits: provides anti-inflammatory effects and induces apoptosis in breast cancer cells.
concerns: more studies are needed for IV usage, infusion rxns reported

Evidence: can bind with iron and decrease bioavailability and increase risk of iron deficiency

• may be beneficial to patients with hemochromatosis
• as a common food component is generally safe and well tolerated when taken orally

Question 16

Reishi mushroom (Ganoderma lucidem)

Answer 16

Bitter fungus with glossy exterior and woody texture- spore powder has bioactive compounds including polysaccharides, triterpenoids, alkaloids, enzymes, and proteins

reported benefits: used to prevent aging, enhance immune system, tx of HTN, HLD, viral infections, cancer, colorectal adenoma, inflammatory disease, CV disease, DM and bronchial disease
Concerns: possibly unsafe when taken for > 1 month, may increase risk of bleeding when combined in high doese with anicoag meds

evidence: small, mostly in vivo/ vitro studies show somne possible anticancer benefits, specifically with breast and lung cancers
- could be administered as adjunct to conventional tx in consideration of it’s potential for enhancing tumor response and stimulating host immunity
- most studied mushroom w/ respect to it’s hepatoprotective effects

Question 17

Resveratrol

Answer 17

Resveratrol (Trans-3,5,4’-trihydroxystilbene) is a naturally occurring stilbenoid, a polyphenol that is considered to be a phytoestrogen with multifaceted biological activities.

reported benefits: antioxidative, anti-inflammatory, antimutagenic, anticarcinogenic, and antiproliferative properties. Has been reported to cause cell cycle arrest, promote apoptosis, and inhibit cancer cell proliferation.
concerns: has antiplatelet effects so could cause excessive bleeding in people on blood thinners

Evidence: animal and clinical studies showed anticarcinogenic effects in colon, liver carcinoma, glioblastoma, prostate, lung, breast, ovaries, oral squam, nonmelanoma skin cancers and thyroid cancer.

• may reduce cisplatin renal toxicities
• may reduce cardiotoxicity with doxil
• may prevent bone loss with MTX when taking 1 mk/ kg body wt

The root of knotweed is a rich source, another good source is grapes, especially dark grapes. Grape skins are particularly rich

Question 18

Selenium

Answer 18

Essential trace mineral found in food

reported benefits: serves as a cofactor for glutathione peroxidase, an enzyme of the antioxidant defense system
concerns: consuming in excess amounts can cause acute toxicity including nausea, vomiting, abdominal pain, dermatitis, nail changes, fatigue, irritability, alopecia, impaired endocrine function, neurotoxicity and wt loss (think of that episode of House where the soldier eats all the Brazil nuts)

Evidence:

• most evidence suggests that Se supplementation does not reduce risk of cancer
• SELECT trial found no effect on prostate cancer, other data showed it increased risks of prostate cancer mortality in men who has 140 mcg or more of selenium daily
• enhances anticancer effects of Cisplatin on breast cancer cells
• may enhance apoptosis from taxol and etoposide and improve tx efficacy

orally, safe and well tolerated at dosages up to the TUI level of 400 mcg/d
selenomethionine is a more bioavailable and preferred form of selenium

Question 19

Silymarin

Answer 19

extract of milk thistle plant. Contains various compounds such as silybin, isosilybin, silychristin, isosilychristin, silydanin and taxifolin. Most studies are on silymarin or silybin, not the whole plant.

reported benefits: acts as an antioxidant, reveals immunomodulatory effects with both immunostimulatory and immunosuppressive effects and liver protective and anticancer effects
concerns: allergic reactions take place at intakes > 1500 mg/d, should be used cautiously in patients on tamoxifen.

Evidence: human studies done for ALL, prostate cancer, breast cancer, and H&N cancer.

• may regulate cell cyles, induce apoptosis, and reduce angiogenesis
• may reduce inflammation and oxidative stress and may protect DNA
• research suggests it may have some anticancer activity, but research is inadequate to recommend it to patients

generally well tolerated. Has poor absorbance and bioavailability due to low water solubility- silibinin-PC is a formulation that’s better absorbed.

Question 20

St. John’s Wort (hypericum perforatum)

Answer 20

a bush that blooms around June 24 (birthday of John the Baptist). Yellow flowers from this bush are used as herbal remedies

Reported benefits: may make cells more sensitive to photodynamic therapies, has antinociceptive and analgesic properties that validate the traditional uses of the plant for pain conditions
Concerns: may interact with Cytochrome P450 3A4, CYP 2C19, CYP 2B6, and others - meds like warfarin, cylcosporine, simvastatin, and amitriptyline

Evidence: may make cancer cells more photodynamic therapy sensitive
- inversely ass with colorectal cancer in VITAL study

Do not recommend, insufficient evidence.
Avoid with ALL concurrent chemo therapies

Question 21

Theanine

Answer 21

Amino acid found in tea and mushrooms

Reported benefits: has antioxidant effects, may enhance docorubicin and idarubicin and reduce their side effects
Concerns: may reduce blood pressure/ interact with antihypertensives

Evidence:

• cell studies suggest it may suppress growth of NSCLC, could help reduce side effects with doxorubicin
• may enhance chemo, but no evidence that supplements is better than theanine in tea
• common dosage is 200-400 mg/d with max dose of 1200 mg/d

Question 22

Turkey Tail mushroom or Yun Zhi (Coriolus Versicolor. Trametes versicolor, Polyporus versicolor)

Answer 22

Bioactive compound from the cultured mycelia of this mushroom include protein- bound polysaccharide- K (PSK) and polysaccharopeptide (PSP)

reported benefits: antimicrobial, antiviral, immunomodulatory and antitumor properties. Ancient chinese formulations of this mushroom have long been believed to promote health, strength, and longevity

Evidence: pretty strong evidence that it can have benefits and help mitigate treatment related adverse effects!

• generally safe and well tolerated
• approved as adjunct therapy in China and Japan for patients receiving chmo/ RT
• • common dosage is 3g but needs standardization
• grows on dead logs worldwide