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Table 3 Descriptions of potential adverse events for non-nutrient based NHPs used by sample based on database search of reported adverse events for each NHP

From: Nutrient- and non-nutrient-based natural health product (NHP) use in adults with mood disorders: prevalence, characteristics and potential for exposure to adverse events

NHP used in sample

Adverse events reported for that NHP in the literaturea

Cranberry (Vaccinium macrocarpon)

More than one litre daily may cause kidney stones [31]. (Note: In this sample, cranberry pills were used and did not exceed this level)

Dehydroepiandrosterone (DHEA) or 5-Dehydro-epiandrosterone (5-DHEA)

People with mood disorders may experience mania, irritability, and sexual inappropriateness [3235]

Devil’s Claw (Harpago-phytum procumbens)

Mild gastrointestinal upset, hypotension, diarrhea, loss of taste, anorexia, headache, and tinnitus [3234]. May interact with warfarin; one case report of purpura [36]

Dong Quai (Angelica sinensis), Chinese angelica

In a cross-sectional survey (n = 1818), one case was identified as a potential significant interaction between dong quai and anticoagulant/antiplatelet agents [37]

Echinacea (Echinacea angustifolia, Echinacea pallida, Echinacea purpurea)

Gastrointestinal upset and rashes; in rare cases, has been associated with allergic reactions that may be severe [38]. May interact with amoxicillin [39]

Evening Primrose Oil (Oenothera biennis)

Case reports of seizures in patients with/without known seizure disorders [40, 41]. In cross-sectional survey (n = 1818), two cases of potential significant interactions with anticoagulant/antiplatelet agents identified [37]

Feverfew (Tanacetum parthenium; syn. Chrysanthemum parthenium (L.) Pers., Pyrethrum parthenium Sm.)

Gastrointestinal upset [42, 43], nervousness, insomnia [44], and possible allergic responses in those sensitive to chrysanthemums, daisies, or marigolds. Potential cross-reactivity with other members of the Compositae family [45]. In cross-sectional survey (n = 1818), two cases of potential clinically significant interactions with anticoagulant/antiplatelet agents identified [37].

Flaxseed (common flax, linseed, Linum usitatissimum)

Rarely, flaxseed (not oil form) has caused gastrointestinal distress [4650]. A double-blind placebo-controlled trial suggested there may be increased episodes of mania and hypomania in people with bipolar disorder [46]

Garlic (Allium sativum)

Breath and body odour, and allergic reactions [51]. Excess use associated with spontaneous epidural hematoma [52]. Potential reactions include bleeding and hypoglycemia (likely not clinically significant) [53]. In cross-sectional survey (n = 1818), 25 cases of potential clinically significant interactions with anticoagulant/antiplatelet agents identified [37]

Ginkgo (Ginkgo biloba)

Surveillance studies (> 10,000 people), found 1.69% incidence of symptoms such as headache and gastrointestinal complaints [54]. Bleeding indicated in a few case reports [55]. May cause allergic hypersensitivity, including Stevens-Johnson syndrome [5658]. In cross-sectional survey of 1818 patients, 20 cases of potential clinically significant interactions with anticoagulant/antiplatelet agents identified [37]. Infrequent mild gastrointestinal discomfort has been reported when Ginkgo is taken with selective serotonin reuptake inhibitors (SSRIs) [59]. May interact with thiazides [60, 61], and nifedipine [62, 63]

Ginseng (American, Asian, Chinese, Korean red; Panax ginseng, Panax spp. including P. ginseng and P. quinquefolius)

Long-term use of Panax and American ginseng associated with skin rash, itching, diarrhea, sore throat, loss of appetite, excitability, anxiety, depression, or insomnia [53, 64]. Few reports of headache, fever, dizziness/vertigo, blood pressure changes, chest pain, difficult menstruation, heart palpitations, leg swelling, nausea, vomiting, manic episodes in bipolar disorder, or Stevens-Johnson syndrome (may have been due to product contaminants) [53]. High intake of American ginseng may result in hypoglycemia in people with/without diabetes [65]. May interact with anticoagulants/antiplatelets [66, 67], diabetes medications [37], digoxin [68], estrogenic agents [6971], furosemide [72], monoaminergic agents [7375], nifedipine [76]

Ginseng (American, Asian, Chinese, Korean red; Panax ginseng, Panax spp. including P. ginseng and P. quinquefolius)

Long-term use of Panax and American ginseng associated with skin rash, itching, diarrhea, sore throat, loss of appetite, excitability, anxiety, depression, or insomnia [53, 64]. Few reports of headache, fever, dizziness/vertigo, blood pressure changes, chest pain, difficult menstruation, heart palpitations, leg swelling, nausea, vomiting, manic episodes in bipolar disorder, or Stevens-Johnson syndrome (may have been due to product contaminants) [53]. High intake of American ginseng may result in hypoglycemia in people with/without diabetes [65]. May interact with anticoagulants/antiplatelets [66, 67], diabetes medications [37], digoxin [68], estrogenic agents [6971], furosemide [72], monoaminergic agents [7375], nifedipine [76]

Melatonin (N-acetyl-5-methoxytryptamine)

May worsen depression and irritability. Sedative medications (CNS depressants) and benzodiazepines interact with melatonin [77]

Omega-3 Fatty Acids, Alpha-Linolenic Acid

Caution indicated for those with diabetes as may increase blood glucose, at risk of bleeding, or with high LDL levels [7885]. May interact with anticoagulants/antiplatelets [80, 8690]

Valerian (Valeriana officinalis)

Mild impairments in concentration, processing, fatigue (less pronounced than with benzodiazepines) [9195], dizziness, and headache [96, 97]. Drug “hangover” and “withdrawal” effect has been reported with high doses [96]. Delirium, ameliorated by benzodiazepines, indicated in one case report [98]. Some develop a “paradoxical reaction” leading to nervousness, and use for longer than 2 months may result in insomnia [53]. Rare reports of hepatotoxicity with some preparations that include valerian [99] but may have been due to other components. May interact with CNS depressants [91, 92, 100]. In cross-sectional survey (n = 1818), 15 cases of potential clinically significant interactions with sedatives identified [37]. One case of SSRI use and valerian (with alcohol) indicated mental status changes [101]

  1. aBased on database searches of MEDLINE, EMBASE, PsychINFO, the Cochrane Library, CINAHL, NAPRALERT, MedEffect™ Canada, International Pharmaceutical Abstracts, CISCOM, and HerbMed for each NHP used in the sample including common and scientific names, synonyms and the primary active constituents of the NHP.