Dr. James Manos (MD)
September 23, 2022
Herbs and Dietary Supplements at a Glance
Frequently Asked Questions (FAQ)
Preamble
Herbs and dietary supplements, like drugs, have indications (we should take them for specific medical issues), contraindications (for instance, regarding pregnant and breastfeeding women, children, senior citizens, and patients), adverse reactions (these may be serious, even life-threatening), interactions (with drugs and other herbs that can enhance or reduce their effectiveness) and dosage. The dose is proportionate to efficacy and should be optimal, based on studies, not sub-optimal. There is, for instance, a difference between herb extracts that have high concentrations and ‘crude’ raw herbs taken as a decoction.
Not all herbs and supplements are safe. Some are dangerous themselves, such as ephedra. Energy drinks may also be unsafe such as the ones containing taurine and caffeine (including guarana, which has twofold caffeine than coffee) for energy-boosting that may cause tachyarrhythmias (a fast heartbeat that may be regular or irregular), while the ones containing creatinine may cause kidney problems.
Regarding herbs, the main concern is whether they are organic or not, as harmful chemicals, including pollutants, exhibit toxic effects. For instance, non-certified organic herbs may contain heavy metals (e.g., lead from white paints and plumbing), pesticides (containing toxins such as arsenic), fertilizers (such as the ones containing organophosphates that may cause severe poisoning), various toxins (including dioxins from burning plastics) and even radioactivity (such as cadmium) from nuclear plants or other sources! The same is true for many supplements, everything edible and water! A characteristic example of a supplement is fish oil which may contain heavy metals harmful especially to pregnant women and children. So, the adverse effects of potential toxins cannot be excluded.
A critical issue is that many companies worldwide import herbs and supplements from China and other regions with dubious safety control. China remains the most polluted country on our planet, and some years ago, Chinese honey was found to contain the ‘melamine’ chemical, possibly contained in the wooden beehive!
Other matters of concern related to herbs and supplements are that they may contain unlabeled substances such as ‘adulterants’ that may be drugs or toxins. For instance, a supplement for sex may contain sildenafil (the same active component of Viagra® that was adulterated to enhance sexual performance). Another example is a ‘red yeast rice’ or a cholesterol-decreasing supplement that may contain a statin (cholesterol-lowering agent) to ensure that its levels will decrease!
All the above raise the importance of quality control of herbs and supplements by independent agencies and the need to be regulated and approved by national drug organizations (including the FDA (Food and Drug Administration)), something that is still not the case! Surveillance from these agencies for adverse reactions is also necessary.
Taking an herb or a dietary supplement is not always safe unless guided by an herbalist (although there is no professional for nutritional supplements). Special groups (such as children, pregnant and lactating women, older adults, and patients) need to consult their doctor before taking them. Presuming that an herb is natural and safe is misleading as often both being natural and safe can be questioned.
Unfortunately, many people take herbs or supplements without consulting a medical practitioner, exposing themselves to potentially adverse effects. Naively, their only ‘guidance’ is the advertisement or commercial of the manufacturer! An example is the herb ‘Echinacea’, advertised as an immune booster for the common cold and flu. The concern is if the dose of the product is optimal to help, as well as the fact that this herb is contraindicated to be taken for more than 7-10 days, while it is not prudent to be taken prophylactically to prevent flu, as some do! Melatonin, used for insomnia and jet lag, is also not advised for prolonged use.
Everything considered, herbs and supplements are not a panacea. They do not treat everything and may not be appropriate or suitable for everyone. Of extreme importance is the quality control by independent agencies and the regulation and approval, as well as vigilance, by national drug organizations, including the FDA.
To put it briefly, SAFETY should come first!
Frequently Asked Questions (FAQ) for herbs and dietary supplements
Are herbs and dietary supplements compatible with modern medicine?
In the past, medications were produced from herbs, such as aspirin from the willow tree (used in ancient Greece), atropine from belladonna (used by women as a cosmetic to dilate their eye pupils), digitalis (digoxin; used for heart problems since 1785) from foxgloves, and senna (for constipation). So, medicine has always used herbs and supplements. The difference from the past is that most drugs are synthetic in modern medicine. But that does not mean that medicine does not still use herbs and supplements. For instance, fish oil is used as a treatment for high blood triglycerides, milk thistle (and its synthetic silymarin) for liver problems (including those from Amanita mushroom poisoning), glucosamine plus chondroitin for knee arthritis, and salmon calcitonin as a nasal spray for osteoporosis.
Herbs and dietary supplements: monotherapy or in combination with modern medicine?
I believe that herbs and supplements should not be used as monotherapy but should be taken in combination with medications unless there may occur interactions. Complementary medicine offers non-medical treatments that can be administered along with modern medicine but with caution on interactions and adverse effects. Otherwise, stopping a medication and replacing it with an herb or a supplement may be catastrophic, even life-threatening. Alternative medicine and contemporary medicine should complement each other. That is the meaning of complementary medicine.
Tthe future of complementary medicine
Currently, western medicine does not include herbs and supplements in medical treatment. Chinese medicine does, while in the West, it seems that herbs are appreciated only in Germany. This combination is for the benefit of the patients. Hopefully, in the future, herbs and supplements will be part of Western medicine. For instance, selenium, zinc, vitamins C & D, Echinacea, elderberry, royal jelly, colostrum, reishi & shiitake mushrooms, Eleuthero, Andrographis, baker yeast, zinc, garlic, and other immune busters could be added to drug treatment for an infection.
Monotherapy or combination?
From my perspective, a combination of herbs and supplements is more beneficial than monotherapy (with a single one) as the beneficial effects are additive.
The difference between herbs and dietary supplements, and how is their effectiveness studied
Herbs are plants that have been used for various conditions, including medical problems. Dietary Supplements are manufactured, while herbs are taken from plants. However, most herbs today are sold as extracts produced as pills, soft gels, etc. Also, many products may contain both herbs and supplements. In a few words, the only natural herbs are only those taken in raw, pure form, such as tea leaves, valerian or astragalus root, etc. Many herbs are vegetables and fruits, such as beetroot and blueberry, respectively.
Some examples of herbs are Stevia (used as a sweetener), huperzine A (used in Alzheimer’s disease), Ginkgo biloba (used as a memory booster and for tinnitus (ear buzzing)), Panax ginseng (used as an energy booster), Astragalus and Eleuthero (called wrongly by some as ‘Siberian ginseng’) (both used as adaptogens, i.e., substances that are supposed to help the body better cope with stress, either mental or physical), Rhodiola rosea (used for fatigue (tiredness), especially stress-related, as well for depression), etc.
Herbs are natural, while dietary supplements may or may not be natural. The latter has been used for various conditions, including medical problems. For instance, idebenone (a synthetic form of Coenzyme Q10) and vinpocetine have been studied for dementia, including Alzheimer’s disease (AD). As with herbs, scientific studies show if a specific dietary supplement helps treat a medical condition better than a placebo, e.g., if SAMe ameliorates arthritis and depression.
Many herbs have been traditionally used for ages. For example, devil’s claw has been used for pain and arthritis, chamomile for its calming effects, and black cohosh for menopausal symptoms. Today scientific studies investigate if herbs and dietary supplements are effective, i.e., if they improve a medical problem better than a placebo (i.e., an inactive substance such as a sugar pill). Randomized controlled trials give scientific proof if a specific herb or dietary supplement improves better than a placebo a disease; for example, if hawthorn berry extract improves heart failure.
Are all herbs & supplements used therapeutically?
Most herbs & supplements are used for the prevention and/or treatment of medical conditions. However, some are not used therapeutically. For instance, Stevia is used as a sweetener, while beetroot is used as a color additive in foods. However, both have additional therapeutical properties.
Are there impressive examples of the beneficial effects of herbs and dietary supplements?
Three striking examples of beneficial properties of herbs and supplements are the herb Hawthorn berry, which has been studied for heart failure; the supplement Coenzyme Q10 which has been studied for various diseases (including the prevention of myopathy in patients taking statins for high blood cholesterol); and the AREDS2 formula (vitamins C&E, zinc, fish oil, and the carotenoids lutein & zeaxanthin) that has been studied for the prevention of the age-related macular degeneration, an eye disease that may lead to blindness.
Is there an overlap between herbs and dietary supplements?
In many cases, there is an overlap between herbs and supplements as manufactured forms, as some are taken naturally, while others are chemically prepared. Herbs are usually natural. For instance, huperzine A is a naturally occurring sesquiterpene alkaloid compound found in the herb firmoss Huperzia serrata. Huperzine A has been investigated for its potential effect on Alzheimer’s disease (AD). However, the memory boosters idebenone and vinpocetine are synthetically manufactured. Idebenone is a synthetic form of Coenzyme Q10, while vinpocetine was produced in Russia as a nootropic. They both have been studied for dementia, including AD.
What is a nootropic?
Nootropic is a substance that may improve cognitive function (executive functions, memory, creativity, or motivation) in healthy people.
Do herbs contain specific ‘active’ substances to which their beneficial role is attributed?
Herbs have ‘active’ substances that explain their health effects. For example, both Asian and American ginseng contain ‘ginsenosides,’ substances that are thought to give ginseng its medicinal properties. Eleuthero (Eleutherococcus senticosus; called wrongly by some ‘Siberian ginseng’) belongs to the same family, but not the same genus, as the true Ginseng. Like Ginseng, it is an adaptogenic herb. The active compounds in Eleuthero are ‘eleutherosides,’ not ‘ginsenosides.’
Other examples are ‘boswellic acids’ (a series of pentacyclic triterpene molecules) produced by the plant Boswellia, used mostly for osteoarthritis, and ‘Kavalactones,’ the main active components in kava – kava root used for anxiety.
A specific herb may contain many substances that are crucial to its beneficial actions. For example, blueberries contain anthocyanins, other pigments, and various phytochemicals (plant chemicals), which are under preliminary research for fighting inflammation and preventing or even fighting cancer.
Interestingly, the carotenoids lutein and zeaxanthin from the herb calendula are two substances with substantial properties. Specifically, the petals and pollen of Calendula officinalis (also known as pot or garden marigold) contain triterpenoid esters and the carotenoids flavoxanthin and auroxanthin, which are antioxidants and the source of the yellow-orange coloration. The leaves and stems contain other carotenoids, mostly lutein (see) (80 percent), zeaxanthin (5 percent), and beta-carotene. Studies have demonstrated that lutein (and its ‘brother’ zeaxanthin in combination) may prevent age-related macular degeneration (AMD/ ARMD), an eye disease that is a common cause of blindness among older adults.
Another example is the herb Uncaria guianensis, known colloquially as cat's claw. It has been used for osteoarthritis, and the various phytochemicals may explain the anti-inflammatory action it contains, including ((-)- epicatechin, alkaloid, beta-sitosterol, campesterol, campherol, catechol, catechutannic acid, chlorogenic acid, ellagic acid, gallic acid, hyperin, oleanolic acid, rutin, stigmasterol, ursolic acid, and proanthocyanidin B1 and B2.
A common herb that we all have tasted is pomegranate (Punica granatum), which has various beneficial health effects, notably, it is an antioxidant and has a favorable impact on the circulation, e.g., it lowers blood pressure. It contains vitamin C, vitamin B5 (pantothenic acid), potassium, and polyphenols such as tannins and flavonoids. The most abundant polyphenols in pomegranate juice are the hydrolyzable tannins called ‘ellagitannins.’ It also contains punicalagins (tannins with free-radical scavenging properties) and other phytochemicals such as polyphenolic catechins, gallocatechins, and anthocyanidins.
Soy (Glycine max) is another famous herb used for various problems, such as reducing blood cholesterol and for menopause problems. Soybeans contain significant amounts of phytic acid, alpha-linolenic acid (a polyunsaturated omega-3 fatty acid), and the isoflavones genistein and daidzein. The last 2 are phytoestrogens and may explain their estrogenic actions, which may also be a matter of concern.
Coffee is a drink that most people enjoy drinking. Its herb contains chlorogenic acid, which is an ester of caffeic acid and quinic acid. It is a primary phenolic compound in coffee and may explain its metabolic effects. Coffee also contains caffeine which also increases the metabolism rate.
Is there a common root for most diseases?
It is believed that ‘free radicals’ are the cause of most diseases. These are molecules produced when the body breaks down food or by environmental exposures like tobacco smoke and radiation. Noteworthy, free radicals can damage cells’ DNA, and affecting the genes may play a role in most diseases, including ischemic heart disease (IHD) and cancer. Herbs or dietary supplements that have high antioxidant capacity scavenge free radicals. This way, they help to prevent or reverse their damage to cells.
Concerning free radicals, what is the role of oxidation?
Oxidation is a chemical reaction that transfers electrons from a substance to an oxidizing agent. Oxidation reactions can produce free radicals. These free radicals can start chain reactions that damage cells.
Can ‘oxidative stress’ contribute to the development of diseases?
Oxidative stress may contribute to the development of a myriad of diseases, including cardiovascular disease, diabetes, rheumatoid arthritis (RA), and neurogenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and motor neuron diseases. However, in many conditions, it is unclear if oxidants trigger the disease or if they are produced as a secondary consequence of the disease and from general tissue damage. Oxidative damage in DNA can also cause cancer. Furthermore, LDL (low-density lipoprotein) oxidation triggers the process of atherogenesis, a condition in which an artery wall thickens because of the accumulation of fatty materials such as cholesterol. Atherogenesis results in atherosclerosis (= hardening of the arteries) and finally cardiovascular disease, a prodrome of heart attack, and stroke.
Which substances are antioxidants?
‘Antioxidants’ are substances that may protect cells against the harmful effects of free radicals, potentially preventing many long-term illnesses. Antioxidants may strengthen blood vessels, improve circulation, and prevent the oxidation of LDL cholesterol (known as ‘bad cholesterol’), a significant risk factor for atherosclerosis (= hardening of the arteries) that leads to coronary heart disease (CHD) that precedes myocardial infarction (= heart attack). An example of an antioxidant is the plant pigment anthocyanosides.
How can antioxidants prevent the formation of free radicals?
Antioxidants can inhibit the oxidation of other molecules and terminate these chain reactions by removing free radical intermediates and inhibiting different oxidation reactions. They achieve this by oxidizing themselves. Thus, antioxidants are often reducing agents such as thiols, ascorbic acid (vitamin C), or polyphenols. Two significant body antioxidants are glutathione (useful for acetaminophen (paracetamol) clearance) and the enzyme superoxide dismutase (SOD).
Can the high antioxidant properties of an herb or a dietary supplement enhance its effectiveness in specific medical conditions?
As mentioned above, free radicals are implicated in many diseases. The antioxidant effect of an herb or dietary supplement may explain its beneficial role in several conditions in which oxidative stress (where free radicals are generated) is implicated. For instance, there are studies that show the useful function of blueberries on blood glucose and blood pressure reduction, their anticancer effects, their preventive role in dementia, their hepatoprotective (liver protective) effects, their anti-aging effects, their neuroprotective role, their role on preventing age-related macular degeneration (AMD/ ARMD; a common devastating eye disease of the older adults), etc. This specific herb acts as a powerful antioxidant and fights the free radicals implicated in most diseases.
That means that it may not surprise us if an herb helps patients with Alzheimer’s disease and simultaneously has anticancer effects and beneficial effects on diabetes mellitus, Parkinson’s disease (PD), inflammatory bowel disease (IBD), and arthritis.
Is there a way to measure the antioxidant capacity of an herb or dietary supplement?
There are several assay methods to measure the antioxidant capacities of foods. These methods are based on different underlying mechanisms and use different radical and oxidant sources. Therefore, no single method exists to measure ‘total antioxidant activity.’ Examples of measurements of antioxidant capacity are the ‘FRAP assay’ which measures ferric ion-reducing activity and the ‘ORAC assay’ which estimates the peroxyl radical scavenging activity. Consequently, the ranking of foods analyzed by the two methods is different, mainly when presented per typical serving size. When the same process interprets similar foods, the variation could be attributed to the application of the technique by different labs, the use of different samples, different cultivars, seasons, harvesting time, etc.
Is the ‘ORAC method’ of measuring antioxidant capacities in biological samples in vitro reliable?
Oxygen Radical Absorbance Capacity (ORAC) measures antioxidant capacities in biological samples in vitro (a lab study regarding a ‘glass tube’ at the lab, not the biology in the body). A wide variety of foods have been tested using this methodology, with certain spices, berries, and legumes rated highly on large tables once published by the USA Department of Agriculture (USDA). However, these were withdrawn in 2012 as biologically invalid, as no physiological proof in vivo (regarding a living organism, not a ‘glass tube’ as in vitro) confirms their effectiveness regarding the free-radical theory. Consequently, the ORAC method, derived only from in vitro experiments, cannot be interpreted as relevant to human diets or biology!
Are antioxidants safe?
Safety is the most critical issue when someone takes an herb or a supplement. Contrary to widespread belief, antioxidants are not always safe. A Cochrane systematic review showed an increased risk of mortality associated with beta-carotene and possibly vitamin E and vitamin A but not with the use of vitamin C or selenium.
Also, although not well defined, there is heavy consumption of tannin-rich foods, mainly sorghum, by populations at substantial risk for carcinoma. The carcinogenic properties of tannins and extracts of tannin-rich plants have been demonstrated experimentally! I guess that this will not prevent you from drinking tea! But green tea remains an excellent antioxidant. The problem is when taking a high dose of an herb or a substance for a prolonged period. So, for tea, a concern may be the high doses of EGCG taken by some to reduce their body weight!
There is also a concern that dietary flavonoids ingested by the pregnant mother may cause later infant leukemia in the first year of life! A study concluded that in utero (in the womb), there may be a critical interval when exposure to elevated levels of flavonoids and increased hematopoietic cell (blood cell precursors) proliferation can lead to recombination involving MLL. Further studies are needed to determine whether the ingestion of common dietary flavonoids by humans results in a similar phenomenon and answer the question of whether increased maternal consumption during pregnancy of foods that contain dietary topoisomerase II inhibitors is positively associated with infant leukemia.
Another significant example is the Beta-Carotene and Retinol Efficacy Trial (CARET), which concluded that CARET participants receiving the combination of beta-carotene and vitamin A had no (chemo)preventive benefit. On the contrary, they may increase lung cancer incidence and mortality! Their results were highly consistent with those found for beta-carotene in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study in 29,133 male smokers in Finland. The trial recommended that individuals at considerable risk of developing lung cancer, i.e., current smokers and asbestos-exposed workers, should be discouraged from taking supplemental beta-carotene (and the combination of beta-carotene with vitamin A).
A systematic review found no evidence to support antioxidant supplements for primary or secondary prevention of diseases while concluding that vitamin A, beta-carotene, and vitamin E might increase mortality! A meta-analysis found that high-dosage (equal to or more than 400 IU daily) vitamin E supplements may increase all-cause mortality and should be avoided!
The use of antioxidants during cancer therapy is currently a matter of debate because of an overall lack of explicit research findings. Some data suggest antioxidants can enhance the toxic adverse reactions of treatment without affecting treatment efficacy, whereas other data indicate antioxidants interfere with radiotherapy or chemotherapy!
Some data indicate that antioxidants may protect tumor cells as well as healthy cells from oxidative damage generated by radiation therapy and some chemotherapeutic agents. A review concluded that the use of supplemental antioxidants during chemotherapy and radiation therapy should be discouraged because of the possibility of tumor protection and reduced survival!
Another interesting result is the one that referred to the postmenopausal (after menopause) women with diabetes who participated in the Iowa Women’s Health Study. The study demonstrated that supplemental (but not dietary) vitamin C intake (at least 300 mg daily) was significantly associated with an increased risk of cardiovascular (related to heart and vessels) disease mortality!
Importantly, high doses of alpha-tocopherol (vitamin E) supplements can cause hemorrhage (bleeding) and interrupt blood coagulation in animals, and in vitro data suggest that high doses inhibit platelet aggregation, meaning that they may increase bleeding tendency. Additionally, a meta-analysis concluded that high dosages (equal to or more than 400 IU per day) of vitamin E supplements might increase all-cause mortality and should be avoided!
Remarkably interesting are the results of studies concerning Zinc (Zn, a trace metal) that demonstrated that it could be harmful at a dose of 80 mg! Zinc can cause copper deficiency, so a small amount of copper should be added to supplements containing significant amounts of zinc. People should be sure to take this combination only under their doctor’s supervision. In the AREDS study for age-related macular degeneration (AMD/ ARMD) prevention, 7.5 percent of people who took zinc had problems, including urinary tract infections (UTIs), enlarged prostate, and kidney stones, compared to 5 percent of the participants who did not receive zinc!
Are there examples of common herbs with safety concerns?
Some herbs such as Echinacea, alfalfa, sprouts, melatonin, and garlic may increase flares of collagen diseases such as SLE. Popular spices are not 100% safe. For instance, black pepper contains the substances safrole and tannic acid, which are weak carcinogens. Also, cinnamon may contain the harmful substance coumarin, which may cause liver cancer. Green tea has also been implicated in some forms of cancer.
The origin of manufactured herbs and supplements
No one knows as the companies do not clarify in which country they are manufactured. A critical issue is that many companies worldwide import herbs and supplements from China and other regions where safety control is dubious, and ISO standards may not exist. China remains the most polluted country on our planet. Often, products are imported from China in powder form. Another issue of concern is that most manufactured herbs are not organic.
Have the traditional uses of herbs been proven scientifically?
Not always have the traditional benefits of herbs been scientifically proven. For example, myriads of properties are attributed to the herb astragalus, even though it increases lifespan! However, only a few of its features have been studied and proven scientifically. Another example is the Greek mountain ‘tea’ (called Sideritis, an herb unrelated to tea), for which research is recent and ongoing. For many herbs, if we search medical research databases, such as PubMed, we may find no study or a few studies that have investigated its traditionally alleged properties. Often, investigations are of low quality to draw a safe conclusion.
Are the suggested benefits of a dietary supplement proven scientifically as well?
Like herbs, the traditional benefits of supplements have not always been scientifically proven. For instance, there is controversy about whether lecithin (e.g., from egg or soy) prevents Alzheimer’s disease or if the amino acid L-carnosine improves epilepsy.
Are studies and meta-analyses of the effectiveness of herbs and supplements conclusive?
Undoubtedly, isolated studies, systematic reviews, and meta-analyses are not conclusive. Isolated research usually says nothing. A systematic review and meta-analysis may show that the analyzed randomized controlled studies (RCTs) regarding the effectiveness of an herb or supplements are few, not of good quality, and with a low sample. Consequently, the lack of well-designed studies is the reason for inconclusive results. Usually reviews and meta-analyses about herbs and supplements usually conclude that more designed studies are needed to reach a safe conclusion.
For instance, older studies and meta-analyses show that huperzine A does not help Alzheimer's patients. But whether it does or not is a matter of how many well-designed studies show its effectiveness or not. Bias is a matter of consideration. A sponsored study by a drug company is not necessarily better than a study on an herb or supplement, as the former may reduce in importance some adverse effects. In contrast, the latter may not be associated with a manufacturer. If it does, it is also biased.
Regarding Alzheimer's disease, drugs are more expensive than herbs. That means scientists may be reluctant to reveal huperzine's neuroprotective effects at the expense of costly medications with many side effects! The same is true for the herb Ginkgo biloba, for which a recent metanalysis, contrary to older studies and metanalyses, shows its beneficial effects on patients with Alzheimer's disease. We should remember that neither drugs nor herbs nor supplements are ideal. Regarding Alzheimer's disease, medications are ineffective in advanced disease, while the cost of monoclonal antibodies is exorbitant.
Are all the published medical studies of good quality?
Unfortunately, although we live in the 21st century, most people, including some doctors, are not skilled enough to read a scientific study and make a conclusion from what they read! The same is true for many journalists who misinterpret scientific research, trying to make it understandable to lay people when they do not understand it themselves. There are a variety of studies published in medical databases. However, some or many studies are not reliable or are not of decent quality.
Their quality depends on several parameters such as if an investigation is an RCT (randomized controlled study), placebo-controlled, and double-blind; if the sample is small (e.g., 5 subjects) or large (e.g., 2,000 subjects); if the duration of the study was short (e.g., 5 days or 2 weeks) or long (e.g., 2 months or 1 year); if the statistical analysis was reliable and were not any statistical flaws (e.g., the published data was insufficient); if there was bias if the study was in vitro (lab studies; on test tubes) or in vivo and, in case of in vivo, if it was a human study or in experimental animals such as rats or mice. Many studies are poorly designed and cannot lead to a safe conclusion. Also, there is a difference between a study, a review, a meta-analysis, a Randomized controlled trial (RCT), a systematic review, a report (e.g., of a specific case), a prospective analysis, etc.
Are some scientific studies biased?
Bias is inevitable, even in the best trial! The key is how extended bias is! An example of bias is when the investigator’s opinion or expectation affects the study, such as in the case where the researcher is determined to prove that a substance helps a medical condition regardless of the negative results! When a biomedical or drug company sponsors the study, the researcher will be especially amenable to bias and manipulation! Manipulation of an investigation is not uncommon, for instance, when the adverse reactions of a substance (especially a drug) are concealed or manipulated statistically while its benefits are exaggerated.
Can a study guarantee the long-term safety of a substance?
The long-term efficacy, toxicity, and adverse reactions of a substance are significant issues that a single study cannot predict. Meantime, patients may start taking a drug or supplement before the pre-referred long-term issues are known, while drug vigilance and surveillance will not prevent unknown adverse effects as their role is retrospective!
Which are the most reliable studies?
Randomized controlled trials (RCTs), which are randomized, double-blind, placebo-controlled, and of good quality, are more reliable in drawing up a conclusion.
What is a placebo?
Placebo is an inactive substance, such as saline solution, distilled water, or sugar, or a less than adequate dose of a harmless substance, such as a water-soluble vitamin, prescribed as if it were an effective dose of the medication needed. Placebos are used in experimental drug studies to compare the effects of the inactive substance with those of the investigational drug.
What is evidence-based medicine (EBM)?
Evidence-based medicine (EBM) analyzes several trials (meta-analyses) and ends up with a safe conclusion if a medication (or an herb or dietary supplement) is beneficial for a specific disease. Evidence-based medicine (EBM) aims to apply the best available evidence gained from the scientific method to clinical decision-making. EBM seeks and assesses the strength of evidence of the benefits and risks of treatment (or lack of treatment) and diagnostic tests. All these help clinicians understand whether a treatment will not harm people.
Evidence quality can be assessed based on the source type (such as meta-analyses and systematic reviews, Cohort studies, and double/ triple-blind, randomized, placebo-controlled clinical trials), as well as other factors, including statistical validity, clinical relevance, accuracy, and peer-review acceptance. EBM recognizes that many aspects of health care depend on individual factors such as quality and value of life judgments, which are only partially subject to scientific methods. EBP seeks to clarify those parts of medical practice that are, in principle, subject to scientific methods and to apply these methods to ensure the best prediction of outcomes in medical treatment.
What is a Cochrane review, and why it leads to a safer conclusion than a single study or a review?
A Cochrane review is a meta-analysis that is published in the Cochrane Library (database) ( http://www.cochrane.org/ ). It analyses all the available published RCTs (randomized controlled studies) from reliable databases, such as Medline ( http://www.ncbi.nlm.nih.gov/pubmed/ and http://www.nlm.nih.gov/ ) that meet the inclusion criteria and concludes if a specific substance (or intervention) helps or not in a particular medical condition. For instance, it may assess if green tea negatively or positively affects cancer incidence and mortality. The conclusion will reflect if the reviewers found RCTs of good quality without statistical flaws. Sometimes a Cochrane review may find few or no RCTs for a specific condition or may find insufficient RCTs.
Consequently, a Cochrane review may conclude reliably about the effects of a substance (herb, dietary supplement, medication) or intervention on a specific medical condition considered only of good quality RCTs. A beneficial effect should be demonstrated that it is better than a placebo for a particular medical condition. Cochrane reviews locate the bias and the quality of a study. For this reason, their importance is significant.
Is the conclusion of a Cochrane review conclusive?
A Cochrane review is not always conclusive and definite as it may conclude that the included RCTs (randomized controlled studies) were not good enough to support a substance's beneficial role. That means that the review found no or a few RCTs or RCTs of not good quality to include them. Various parameters may affect a trial negatively, such as the small sample, statistical flaws, inadequate analysis of the results, problematic follow-up, conflict of interest, sponsored trials, etc. Often, a Cochrane review may conclude that more RCTs are needed to demonstrate the effectiveness of an herb/dietary supplement on a medical condition.
People without medical knowledge should read a Cochrane review carefully and not just skim through or read the abstract. For example, a review may refer to some studies that showed the beneficial effects of an herb/ dietary supplement on a medical condition. However, taking into consideration all the facts and data, the author of a review may conclude that the evidence from RCTs is still inconclusive about its beneficial role.
An example is huperzine A, a substance from the herb Huperzia serrata. The failure of a 2012 Cochrane review to prove that it really helps in Alzheimer’s disease (AD), although the data from pre-existing studies may show some beneficial effects, may just reflect the fact that there is a lack of large and good-quality human RCTs to support the effectiveness on the prevention/ treatment of AD. That means future human RCTs of good quality may prove or may not demonstrate that this herb enhances memory, specifically in AD.
We must remember that things are not static but change daily. A new Cochrane review may make a different conclusion than an older one for the same subject.
Are scientific studies conclusive? Does a single randomized controlled trial (RCT) lead to a safe conclusion?
Scientific studies are not conclusive in the time that research is published every day, meaning that a new study may change things.
A single randomized controlled trial (RCT) cannot lead to a safe conclusion unless it is confirmed by following good-quality RCTs.
Are there any reliable sites where someone can read a scientific study?
Are there any reliable sites where someone may find information about herbs and dietary supplements?
Have herbs and dietary supplements specific indications?
Herbs and dietary supplements usually have specific indications. For instance, omega-3 fatty acids (EPA and DHA) found in fish oil may be beneficial for rheumatoid arthritis and systemic lupus erythematosus (SLE) (both collagen diseases), osteoporosis (bone density reduction predisposing to fractures, especially of the hip), depression, bipolar disorder (mania with depression), schizophrenia, attention-deficit/ hyperactivity disorder (ADHD; a common childhood disease that I think it is over-diagnosed), skin disorders, inflammatory bowel disease (IBD; Crown’s disease and ulcerative colitis (UC)), asthma, age-related macular degeneration (AMD/ ARMD), menstrual pain, breast, colon and prostate cancer, osteoarthritis and other infirmities. Omega-3 Polyunsaturated Fatty Acids (PUFAs) from fish oil have also been investigated for the treatment of IgA nephropathy.
Is there scientific research to prove the effectiveness of herbs and dietary supplements in treating diseases?
Scientific research has to prove the effectiveness or not of herbs and dietary supplements in treating diseases. An example is fish oil that, in high doses, is used for the treatment of high blood triglycerides that cause coronary heart disease. Another example is sickle cell disease. This disease is caused by a mutation regarding a single nucleotide substitution in the codon for amino acid 6. This change converts a glutamic acid codon to a valine codon. L-glutamine is an α-amino acid used in the biosynthesis of proteins. Its side chain is like that of glutamic acid, except the carboxylic acid group is replaced by an amide. L-glutamine is a precursor of the antioxidant glutathione and has been approved by the FDA for the management of sickle cell anemia.
Is there a classification of the effectiveness of herbs and dietary supplements?
The MedlinePlus ( http://www.nlm.nih.gov/medlineplus/ ) rates the effectiveness of an herb or a dietary supplement as ‘likely effective’ or ‘possibly effective,’ ‘possibly ineffective,’ or ‘insufficient evidence to rate the effectiveness for a particular medical condition or that there is insufficient evidence to prove it.
Do herbs and dietary supplements have contraindications?
Most herbs and dietary supplements have contraindications. For example, most herbs and nutritional supplements are contraindicated in pregnant and breastfeeding (lactating) women, and many are contraindicated in children. Others are contraindicated in specific populations, such as senior patients and those with diabetes mellitus, heart problems, or hypertension. Many herbs and dietary supplements are contraindicated in patients taking medications such as sugar-lowering medication for diabetes or blood – thinners (for atrial fibrillation, a heart arrhythmia that may lead to stroke or an implanted heart valve).
An example of a supplement with contraindications is glucosamine which is not recommended for children as it is mainly used to treat osteoarthritis (a condition that affects adults), and its safety for children has not been studied. It is also contraindicated in people with seafood allergies, as well as in pregnancy and breastfeeding. Another example is the herb Goldenseal is contraindicated in newborn babies because it is likely unsafe for them, as it may cause severe brain damage (kernicterus; this may also occur from Rhesus hemolytic disease). Green tea is a common herb. It contains caffeine, tannins, and other substances and is contraindicated (should not be taken) on people with heart problems, kidney disorders, stomach ulcers, and psychological disorders, particularly anxiety.
Generally, most herbs and dietary supplements are contraindicated in pregnancy, lactation (breastfeeding), and children. Many are contraindicated in the elderly (to whom they have not been studied) or in specific diseases, including hypertension (high blood pressure) and diabetes mellitus (we call it mellitus to differentiate it from insipidus). For instance, people with hypertension and diabetes should not take ginseng products without the close supervision of their doctor as it may increase their blood pressure (but some species may lower it) or lower blood sugar. Also, people with low blood pressure and those with an acute illness should use American ginseng with caution.
Are there herbs and dietary supplements that have been used widely?
Some herbs and dietary supplements that have been widely used are lecithin and soy. For example, lecithin is approved by the FDA (Food and Drug Administration) for consumption under the term ‘generally recognized as safe.’ Lecithin is admitted by the EU (European Union) as a food additive with the E number E322. It is used with food, as an additive, or in food preparation. It is used commercially in foods requiring a natural emulsifier or lubricant.
Another example is curcumin, the principal curcuminoid from the Indian spice turmeric (Indian saffron) responsible for turmeric's yellow color. Curcumin has been used as a yellow coloring for foods. As a food additive has in the EU the number E100. Curcumin, the yellow color pigment of turmeric, is produced industrially from turmeric oleoresin.
Which is the most common interaction with medicine? Can this affect people not taking drugs?
The most common interaction of many herbs and some supplements is that they may enhance the effects of blood thinners, including warfarin, heparin, modern anticoagulants (such as dabigatran), and antiplatelets (such as aspirin). This combination may predispose to bleeding. People taking blood thinners should not take specific supplements such as glucosamine & chondroitin (the latter is a heparin analog) for arthritis, Ginkgo Biloba for memory, pycnogenol for varicose veins, etc. The problem is that the interaction may occur even to a normal person if, for instance, takes for a brief time a medicine such as a non-steroidal anti-inflammatory drug (NSAID) for pain and inflammation or other drugs that may slow blood clotting. The most potent herbs for this interaction are glucosamine & chondroitin and Ginkgo Biloba. Many herbs and supplements affect blood clotting in people not taking medicine. But for those taking specific drugs (antiplatelets, anticoagulants, cortisone, NSAIDs, antidepressants, and others), this interaction may be dangerous as it predisposes to bleeding.
Are all herbs and dietary supplements safe?
Not all herbs and dietary supplements are safe! The widespread belief that herbs are natural and, for this reason, they do not have adverse reactions is misleading and often wrong. The safety of many herbs and dietary supplements is debated. For example, the herb Black Cohosh, used for menopausal symptoms, has been associated with liver problems. The Pacific herb kava-kava used for anxiety may also be hepatotoxic (exhibit liver toxicity). The herb 'chaparral' is also unsafe, as it can cause kidney and liver problems and severe poisoning. Regarding poisoning, some herbs such as mushrooms Amanita phalloides collected from nature by somebody who cannot distinguish the poisonous from the edible form may cause life-threatening poisoning. Even bitter almonds may cause severe poisoning as they contain cyanide!
Some herbs and dietary supplements or their combination may have severe adverse reactions. For instance, there is a report of a stroke on an athlete who consumed creatine monohydrate 6 grams, caffeine 400-600 mg, ephedra 40-60 mg, and a variety of other supplements daily for six weeks. Also, rhabdomyolysis (the breakdown of skeletal muscle tissue) and acute renal failure (sudden kidney failure) were reported in one case involving an athlete taking more than 10 grams daily of creatine for six weeks. Another report describes a 63-year-old female who presented with fulminant hepatic (liver) failure requiring liver transplantation caused by a weight-loss dietary supplement containing conjugated linoleic acid (CLA). Importantly, in some cases, it is not the herb or supplement per se that causes problems but potential (and potent) ‘adulterants,’ substances that the manufacturer has added!
Another example of safety concern is the famous memory-booster Ginkgo biloba which may increase the risk of bruising and bleeding, especially in people with bleeding diathesis (tendency), as it acts like blood thinners! In a few people taking ginkgo, bleeding into the eye and the brain and excessive bleeding following surgery were noticed as severe adverse effects. But these cases are scarce.
Aloe vera is an herb that has been advertised for treating everything, from osteoarthritis to increased blood fat. However, there is a lack of evidence for most of the alleged beneficial effects, apart from skin problems! Taking aloe latex by mouth can reduce constipation and cause diarrhea. However, it may cause loss of potassium from cells lining the intestine, resulting in paralysis of the walls of the intestine, making bowel movement difficult! Taking large doses of aloe latex or using it for a long time can be dangerous, so the FDA (Food and Drug Administration) of the USA took laxatives that contained aloe latex off the market in 2002.
A characteristic example of an unsafe herb is goldenseal. There is little information about the safety of high dosages or the long-term use of goldenseal. Noteworthy, a study showed that goldenseal root powder increased the risk for liver tumors in rats and mice, while another study showed that the administration of goldenseal root powder resulted in increased incidences of non-neoplastic lesions in the liver of male and female rats and male mice! Both studies imply that this herb may be carcinogenic, i.e., it may cause cancer.
Another example is fish oil which contains the notorious omega-3 fatty acids (EPA and DHA). Fish oil is likely safe for most people, including pregnant and breastfeeding women, when taken in low doses. However, taking high doses of fish oil is possibly unsafe as more than 3 grams (higher than the recommended dose of 1 gram daily) per day might keep blood from clotting and can increase the chance of bleeding!
Is there a specific classification regarding the safety of an herb or dietary supplement?
The MedlinePlus ( http://www.nlm.nih.gov/medlineplus/ ) classifies a specific herb or dietary supplement as ‘likely safe’ or ‘possibly safe’ or ‘unsafe’ for a particular medical population (such as patients taking blood thinners) or a specific part of the population (such as children, pregnant and breastfeeding women).
For example, Chromium is likely safe for most adults when used appropriately for six months or less, but it is possibly safe for most people when used for more extended periods. Another example is Panax Ginseng which is contraindicated in pregnant women as it is possibly unsafe because one of the chemicals in Panax ginseng has been found to cause congenital disabilities in animals. Also, Panax ginseng is likely unsafe in infants and children. It is also contraindicated in infants, as using Panax ginseng in babies has been linked to poisoning that can be fatal. The safety of Panax ginseng in older children is not known, so its safety is not guaranteed for children.
Are there concerns about the long-term safety of herbs and dietary supplements?
A worrying issue is the long-term safety of herbs and dietary supplements. For many, it has not been assessed, as most studies evaluate the safety of an herb or a dietary supplement only for a brief time. Consequently, many herbs and nutritional supplements may cause adverse reactions and even toxicity if taken for a long time, especially in high doses.
For example, there is little information about the safety of high dosages or the long-term use of goldenseal. A study showed that goldenseal root powder increased the risk of liver tumors in rats and mice. Another example is melatonin which many people take for insomnia (sleeping difficulty), although its effectiveness has been better studied on jet lag. Melatonin is safe only when taken for three months or less, as its long-term safety has not been evaluated.
Herbs with low safety profiles are, for example, pennyroyal, nutmeg, juniper, ephedra (dangerous), Black Cohosh (causes liver problems), Yohimbine (taken for sex), wormwood (causes absinthism), etc.
Dietary Supplements & anabolic steroids for muscle gain and improving athletic performance
Many, if not most, bodybuilders wish to have a beefy body fast. The same is true for many athletes. However, a stocky body and better performance are impossible without supplements, many of which have serious adverse effects. Many athletes usually consult ''Dr. Google'' and buy supplements online or ask their trainers about them.
But they omit to ask a healthcare professional if they are safe! Anabolic steroids have numerous side effects. Many consume excessive amounts of animal products, including meat, eggs, and dairy products, which are harmful as they elevate blood cholesterol and triglycerides, increasing the chance of heart disease. Processed meat is also carcinogenic, namely causing cancer! Protein supplements may also contain excessive amounts of lipids (fats), including harmful saturated fats.
Regarding the kidneys, creatine's safety is questioned. Protein, usually taken in powder forms, may also be harmful to the kidneys at exceedingly high doses (e.g., 50 grams). Other supplements such as ephedra, caffeine & guarana, thyroxine & iodine, and diuretics (taken to lose weight can even cause death. People who exercise think that taking a supplement will boost their energy and build up their muscles instantly, like Popeye eating spinach! But safety should count first!
From my point of view as a medic, the only supplements that I recommend are spirulina & chlorella (both are algae), royal jelly (unless someone is allergic to honey products), arginine (people with heart problems should avoid it) & carnitine (the previous 2 are amino acids), tart cherry (helps muscle recovery), beetroot (helps oxygen utilization by the muscles), coenzyme Q10, and pycnogenol. The last is contraindicated on people taking blood thinners. Herbs such as Eleuthero and Rhodiola may help as adaptogens.
In any case, athletes should consult a doctor other than their personal sports medicine doctor before taking a supplement, as some dietary supplements may be deadly! In any case, they should NEVER take anabolic steroids, ephedra, thyroxine (and iodine), guarana (which has elevated levels of caffeine that may cause arrhythmia), and diuretics. The most hazardous supplements are ephedra and anabolic steroids, as they can even cause death.
Are toxicology tests needed to investigate the safety of an herb or dietary supplement?
Although toxicology tests are needed to investigate the safety of an herb or a dietary supplement, they do not exist for many, if not most, herbs and nutritional supplements. For instance, black cohosh rhizome (Actaea racemosa) has been used as a remedy for pain and gynecological ailments. However, due to its widespread use and lack of safety data, black cohosh was nominated to the National Toxicology Program (NTP) for toxicity testing. The NTP characterized several commercially available black cohosh extracts (BCE). BCE-induced dose-dependent hematological (blood) changes in both rats and mice. These effects were more severe in mice, especially at doses above 125 mg/kg. Dose-dependent thymus (a gland) and liver toxicity were observed in rats but not mice, while puberty was delayed 2.9 days at the highest treatment dose in rats. A similar magnitude delay in mice occurred in the 125 and 250 mg/kg groups but not at the higher doses.
Moreover, the European Medicines Agency (EMEA) and the Committee on Herbal Medicinal Products (HMPC) in July 2006 released an alert to make European sanitary authorities aware of forty-two cases of suspected hepatotoxic (toxicity to the liver). In the public statement, EMEA itself was considered reliable as hepatotoxic reactions in only four cases based on the RUCAM score: two were deemed possible and two probable.
Interestingly, a study investigated the influence of the crude aqueous extract of papaya (Carica papaya) seeds was studied on semen profile, fertility, body and organ weight response, and toxicology in male albino rats. The study concluded that papaya seed aqueous extract treatment could induce reversible sterility in male rats.
Is a ‘washout’ period necessary for those taking an herb or a dietary supplement?
Many experts advise a washout period for consumers of herbs or dietary supplements, meaning that they are encouraged to stop taking the substance for some weeks. The time of washout depends on the studies, as there are no guidelines for a specific period.
For example, a double-blind, placebo-controlled crossover study investigated the efficacy of Korean red ginseng for erectile dysfunction using the International Index of Erectile Function. A total of 45 patients with a clinical diagnosis of erectile dysfunction participated in the study. The patients took eight weeks of treatment, two weeks of washout, and eight weeks of treatment.
Another double-blind, cross-over study determined the impact of very-long-chain inulin (VLCI), derived from globe artichoke (Cynara scolymus), on the human intestinal microbiota compared with maltodextrin. The study was carried out in thirty-two healthy adults who were randomized into two groups for two 3-week study periods, separated by a 3-week washout period.
Another study investigated whether cinnamon improves blood glucose and blood lipids (fats) in people with type 2 diabetes. A total of sixty people with type 2 diabetes participated in the study. Cinnamon was consumed for 40 days, followed by a 20-day washout period.
Can herbs and supplements be taken every day?
For many herbs and supplements, their prolonged use is not recommended. An example is the herb ‘Echinacea’, which is advertised as an ‘immune booster’ for the common cold and flu. The concern is if the dose of the product is optimal to help, as well as the fact that this herb is contraindicated to be taken for more than 7-10 days, while it is not prudent to be taken prophylactically to prevent flu, as some do! 'Melatonin,' a hormone used for insomnia and jet lag, is also not advised for prolonged use.
Are there any natural detoxifiers?
It is said that spirulina is a detoxifier, but it should be organic and not contain harmful substances themselves! The most popular detoxifier is zeolite, a mineral resembling lime that has numerous porous that explain its absorbance. Zeolite theoretically absorbs all noxious substances but leaves the beneficial ones, including metals and vitamins. It is said that the best quality is that from Thrace (a region in the Balkans). It can be consumed as a manufactured powder mixed with water. Someone may even wash vegetables and fruits in water mixed with zeolite to absorb all the noxious substances, such as pesticides. However, there is a lack of evidence that zeolite may exhibit these in vivo absorbance capacities for detoxification.
Do herbs and supplements contain toxins? Are some herbs harmful?
Regarding herbs, the main concern is whether they are organic or not, as harmful chemicals, including pollutants, exhibit toxic effects. For instance, non-certified organic herbs may contain heavy metals (e.g., lead from white paints and plumbing), insecticides and pesticides (containing toxins such as arsenic), coumarin, fertilizers (such as the ones containing organophosphates that may cause severe poisoning), various toxins (including dioxins from burning plastics) and even radioactivity (such as cadmium) from nuclear plants or other sources! The same is true for many supplements, everything edible, and water! A characteristic example of a supplement is fish oil which may contain heavy metals harmful especially to pregnant women and children. So, deleterious effects from potential toxins cannot be excluded.
Other toxic substances include the carcinogenic ethylene oxide (used for sterilization), microbes (bacteria, fungi, viruses, e.g., an unsterilized herbal skin preparation may contain bacteria such as Pseudomonas while an herb may contain fungi), plant alkaloids (although some are used against cancer, they may have serious adverse effects), antibiotics, polycyclic aromatic hydrocarbons (including benzenoid hydrocarbons; they are carcinogens), dioxins, melamine (found in various foods as a deliberate adulterant to increase the protein content or as a contaminant) and medications.
A critical issue is that many companies worldwide import herbs and supplements from China and other regions where safety control is doubtful. China remains the most polluted country on our planet, and some years ago, honey was found to contain the ‘melamine’ chemical, possibly containing beehives!
Other matters of concern related to herbs and supplements are that they may contain unlabeled substances such as ‘adulterants’ that may be drugs. For instance, a supplement for sex may contain sildenafil (the active component of Viagra™) to enhance sexual performance or a ‘red yeast rice’ supplement may contain a statin (cholesterol-lowering agent) to reduce cholesterol or to ensure that its levels will decrease!
Birthworts (family Aristolochiaceae) are an example of dangerous herbs. It contains aristolochic acid, which may damage the kidneys and cause liver cancer. Fish oil supplements may also be harmful when they contain heavy metals, which may have severe implications for pregnant women. Vinpocetine is advertised as a memory booster. It is a vinca alkaloid. These alkaloids are also used in cancer treatment but have many side effects. Vinpocetine may cause agranulocytosis, a severely lowered white blood cell count. That causes immunosuppression predisposing to infections.
The herb Black Cohosh, used for menopausal symptoms, has been associated with liver problems. The Pacific herb kava-kava used for anxiety may also be hepatotoxic (exhibit liver toxicity). The herb 'chaparral' is also unsafe, as it can cause kidney and liver problems and severe poisoning. Regarding poisoning, some herbs such as mushrooms Amanita phalloides collected from nature by somebody who cannot distinguish the poisonous from the edible form may cause life-threatening poisoning. Even bitter almonds may cause severe poisoning as they contain cyanide!
Can herbs and supplements cause poisoning?
Not all herbs and supplements are safe. Some are dangerous themselves, such as ephedra. The herb 'chaparral' is also unsafe, as it can cause kidney and liver problems and severe poisoning. Regarding poisoning, some herbs such as mushrooms Amanita phalloides collected from nature by somebody who cannot distinguish the poisonous from the edible form may cause life-threatening poisoning. Even bitter almonds may cause severe poisoning as they contain cyanide!
Are all energy drinks safe?
Some energy drinks may be unsafe such as the ones containing taurine and caffeine (including guarana, which has twice as much caffeine as coffee) for energy-boosting that may cause tachyarrhythmias (a fast heartbeat that may be regular or irregular), while the ones containing creatinine may cause kidney problems.
Are gym supplements safe? What are the author’s recommendations?
Some energy drinks may be unsafe such as the ones containing creatine (they may harm the kidney) as well as the ones containing taurine and caffeine (such as from guarana) for energy-boosting that may cause tachyarrhythmias (a fast heartbeat that may be regular or irregular). People at the gym are sometimes extremely reckless, as they may take anabolic-like substances to enhance their muscle mass. These products are not only unlicensed but may be harmful. I remember a veteran cyclist who was a supplement maniac and searched to purchase online an unknown to me chemical that had cyanide (a poison)-like properties aiming at increasing blood hematocrit by causing polycythemia from anoxia (oxygen deprivation) as cyanide has a higher affinity and displaces oxygen in hemoglobin!
Potentially harmful are the extremely elevated levels of protein (and nitrogen) that some take for muscle bulking as there is a consideration that they may harm the kidneys, especially if malfunctioning (e.g., in older individuals or those with pre-existing renal problems or those taking medications that may affect the kidneys).
It should be noted that some beef meat powder or whey protein products may contain significant cholesterol levels that are harmful to circulation. However, most companies try to sell products with a low fat percentage.
For the gym, I recommend taking only organic spirulina powder and soy powder for protein supplementation but keep in mind that the latter contains phytoestrogens. It will lower cholesterol levels, but there is a concern that it may cause problems with plant estrogens. Beetroot and manufactured tart cherry (especially the Montgomery) may also help the performance and recovery, respectively.
Are supplements for enhancing sexual performance safe?
Some supplements for enhancing sexual performance may be safe. These include arginine and pycnogenol (pine bark extract). However, many products for sexual dysfunctions or sex boosters are unsafe. Some may contain adulterants, i.e., unlabeled substances or unknown contaminants. For instance, a supplement for sex may contain sildenafil (the active component of Viagra™) to enhance sexual performance. A harmful substance is Yohimbine which acts as an a2-receptor antagonist and may cause tachyarrhythmia (rapid heartbeat), hypertension (increased blood pressure), mydriasis (eye pupil dilation – such as when taking cocaine), diaphoresis (perspiration), lacrimation (tears), salvation (excess saliva), nausea and vomiting (N&V), and flushing.
Can herbs and dietary supplements cause adverse reactions?
Many herbs and dietary supplements cause adverse reactions. But, from my experience, adverse reaction risk is higher when someone takes the natural crude, raw form of the herb rather than the manufactured form (pill, discs, capsules – often as extracts), apart from potential adverse reactions from tinctures and natural juices containing ‘fresh’ herbs. A reason for this is that the dose of a manufactured product may be low (and sub-optimal) compared to the natural herb. However, this does not apply to manufactured herb extracts that are highly potent. Regarding supplements, they are usually manufactured, not natural, so they may cause adverse reactions. For example, lipoic acid and EGCG (from green tea) may cause stomach and esophagus discomfort.
In any case, manufactured forms may still cause adverse reactions as they may contain pollutants, toxins, and ‘adulterants.’ The same may be true for herbs. That means regardless of taking a natural or manufactured herb, adverse reactions should always be taken into consideration, and consumers should be alert and stop taking the specific herb if they occur.
Adverse reactions are rated as common, relatively common, uncommon, rare, and exceedingly rare (however, ones related to medications are better studied and are usually accompanied by the percentage of people exhibiting them). For instance, adverse reactions to Ginkgo biloba include increased bleeding risk (especially in patients taking blood thinners) and has as adverse reactions nausea, vomiting, diarrhea, dizziness, palpitations, headache, and restlessness. It may also cause constipation, tachycardia, and allergies (such as contact dermatitis), especially in people with pre-existing allergies.
Some herbs have more common adverse reactions than others, but no herb has zero adverse effects. For example, milk thistle is an herb used traditionally for liver problems. It can cause some adverse reactions such as nausea, diarrhea, indigestion, intestinal gas, bloating, fullness or pain, and loss of appetite, while sometimes causing a laxative effect or allergy (usually with the plant rather than taking a manufactured form).
A significant adverse effect may occur with licorice, an herb taken for various conditions. The natural form contains glycyrrhizin which may cause serious adverse effects. Specifically, glycyrrhizin may cause a disease called pseudo-aldosteronism, an increased sensitivity to a hormone in the adrenal cortex. This condition can lead to headaches, fatigue, hypertension (high blood pressure), metabolic alkalosis, and even heart attacks. It may also cause water retention, which can lead to leg swelling and other problems. For this reason, deglycyrrhizinated licorice (DGL) has been described as a safer choice. However, comprehensive safety studies on DGL have not been reported.
Is there an exaggeration regarding the adverse events of herbs and dietary supplements?
Often medical sites refer to adverse reactions of herbs and dietary supplements that are theoretical or even anecdotal instead of documented and published adverse reactions. Adverse effects are often supposed without evidence but with exaggeration, such as the theoretical concern that herbs and supplements that boost the immune system may stimulate it, which may cause cancer.
Are herbs and supplements safer than drugs?
Compared with medications, herbs and supplements have fewer adverse effects, with some exceptions. Allergy is an issue, but incidences are fewer with manufacturer products compared to raw natural herbs unless they contain 'adulterants' and toxins such as environmental pollutants.
Do drug companies compete with herbs and supplement manufacturers?
Drug companies manufacture drugs that are initially patented. On the contrary, herbs and supplements are free to everyone and are not patented unless they have a special formula, such as EpiCor(R), used for immune defense. Many drug companies also produce herbs and supplements. In any case, it may be in the interest of drug companies when the side effects of an herb or supplement are overstressed. However, it is obvious that drugs have numerous side effects, more than the widely used herbs and supplements.
Is evidence conclusive of the effectiveness of herbs and supplements?
A critical issue is that by using isolated studies or metanalyses of poorly designed studies, many try to underestimate and degrade the effectiveness of herbs and supplements when in fact, it is the studies that have flaws. An herb may be used for hundreds of years by traditional medicine. So, it is obvious that its effects might be beneficial to explain its traditional use in the past. On the other hand, studies of medicine may be biased, with conflict of interest, and may present misleading results by omitting adverse reactions and side effects.
Are herbs and supplements related to drugs?
It is well known that many drugs are related to herbs, from aspirin (willow bark) and opioids (opium) to atropine (Belladonna), alkaloids (such as the supplement vinpocetine), etc. Some herbs have excellent efficacy, such as the artemisinin derivatives used for malaria showing resistance in many antimalarial drugs!
Which are the most common adverse reactions to herbs and dietary supplements?
The most common adverse reactions to herbs and dietary supplements are allergy and gastrointestinal (GI) disturbance (usually when taken orally, i.e., by mouth), while allergy may also occur with topical forms (e.g., cream or ointment). Allergic people should not take dietary supplements or herbs to which they are allergic, as well as herbs from the same family. People with a pre-existing allergy (such as to nuts or seafood) or atopy are more likely to exhibit hypersensitivity when taking an herb. An example of this is chamomile. People sensitive to asters, daisies, chrysanthemums, or ragweed may also be allergic to chamomile. Roman chamomile may cause an allergic reaction in people who are sensitive to the Asteraceae/ Compositae family. Members of this family include ragweed, chrysanthemums, marigolds, daisies, and many others.
It seems that allergy risk is higher when someone takes the natural raw form of the herb rather than the manufactured form (pill, discs, capsules – often as extracts), except for potential allergies from tinctures and natural juices containing ‘fresh’ herbs.
Often reactions are baptized by an individual as ‘allergy’ but are an adverse reaction or hypersensitivity to a substance/ food rather than a true allergy. It may also be a reaction to gluten (in case the product is not gluten-free, and the person has coeliac disease or predisposition), lactose, etc.
As many herbs and supplements have contraindications and adverse reactions, people should consult their doctor before taking them. For example, before someone takes omega-3 fatty acids, they should ask their physician if allergic to omega-3-acid ethyl esters; fish, including shellfish (clams, scallops, shrimp, lobster, crayfish, crab, oyster, mussels, others); any other medications; or any of the ingredients in omega-3-acid ethyl ester capsules.
Not all herbs and supplements are safe. Some are dangerous themselves, such as ephedra. Energy drinks may also be unsafe such as the ones containing taurine and caffeine for energy-boosting that may cause tachyarrhythmias (a fast heartbeat that may be regular or irregular) while the ones containing creatinine may cause kidney problems.
Allergy issues
The most important thing is to avoid herbs and supplements that may cause anaphylaxis, a life-threatening condition with difficulty breathing (stridor from larynx swelling) from angioedema, rash, and severe hypotension (low blood pressure). Allergy usually occurs at the second, not the first, exposure to the allergen.
Rarely, herbs and supplements may cause anaphylaxis, a life-threatening allergic reaction. Some examples of herbs and supplements that may cause anaphylaxis in allergic people are chamomile, glucosamine (from shellfish), Echinacea, etc. Importantly, the allergy will occur to susceptible people, such as those with atopy, but not everyone. However, almost everyone can have an allergy to something, from bees, shellfish, nuts, glove latex, and even sperm. The key feature is if the patient has a pertinent history of any allergy, something that should ALWAYS be asked. If yes, it should be made clear if this was a true allergy and not intolerance and if it was severe, i.e., life-threatening anaphylaxis.
Avoiding hypervitaminosis
Although we all need vitamins for our body's proper function, when these are consumed in excess, they cause hypervitaminosis, i.e., high vitamin levels that may cause medical problems. It is essential to consider that vitamins are usually taken prophylactically to prevent diseases. But often, they are taken as a treatment. So, hypervitaminosis is a negative result that may involve healthy or ill people.
Hypervitaminosis may occur, for example, from excessive intake of Vitamin A, D, E, C, B3 (niacin, more than 2 grams), B6 (more than 1 to 3 grams), etc. For instance, excessive doses of vitamins A and C may increase blood calcium which causes medical problems. For the prevention of hypervitaminosis, the dosing should not exceed the Recommended Daily Allowances (RDAs). Consumers should be informed about RDAs, Adequate Intakes (AIs), and Upper Tolerable Intake Levels (ULs). These depend on age, gender, and life stage. If ULs are surpassed, then toxicity may occur.
Do herbs and dietary supplements have interactions with medications, other herbs & nutritional supplements, food, and alcohol?
Most herbs and dietary supplements interactions have interactions with medications, other herbs & dietary supplements, food, and alcohol. These interactions may be severe. For example, there is a report of stroke in an athlete who consumed creatine monohydrate 6 grams, caffeine 400 – 600 mg, ephedra 40 – 60 mg, and a variety of other supplements daily for six weeks.
Another example of interactions is with Ginkgo biloba, an herb that can increase the anticoagulant effect of warfarin and other anticoagulants (blood thinners) and antiplatelets (such as aspirin and clopidogrel) drugs, so it should be avoided in patients using these drugs.
Green tea is a commonly used herb. However, significant interactions with green tea may occur with medications, other herbs, supplements, food, and minerals. Specifically: a) Amphetamines and cocaine. Stimulant drugs such as amphetamines and cocaine can speed up the nervous system. Taking green tea along with stimulant drugs may cause severe problems, including increased heart rate and high blood pressure. Stimulant drugs should not be taken along with caffeine. b) Ephedrine. Taking green tea along with ephedrine may cause too much stimulation and sometimes severe adverse reactions and heart problems. Caffeine-containing products and ephedrine should not be taken at the same time. Interactions with herbs and dietary supplements may occur with a) Bitter orange. b) Caffeine-containing herbs and supplements. c) Creatine. There is some concern that combining caffeine, ephedra, and creatine may increase the risk of severe unwanted adverse reactions. One athlete who used this combination and some other supplements to improve his performance suffered a stroke. d) Ephedra (Ma Huang). Green tea should not be taken with ephedra. The caffeine in green tea may increase the effects of ephedra. Using ephedra with caffeine might increase the risk of life-threatening or disabling conditions such as hypertension, heart attack, stroke, seizures, and death. e) Folic acid. f) Herbs and supplements that might harm the liver. g) Iron. Interactions with foods may also occur with a) Iron. Green tea appears to reduce the absorption of iron from foods. b) Milk. Adding milk to tea seems to cut some of the tea’s benefits for the heart and blood vessels. c) Calcium. Drinking green tea can increase the amount of calcium that is flushed out in the urine.
Alcohol may also interact with herbs and dietary supplements such as Red Yeast Rice, kava, etc.
Which herbs have more frequent interactions with medications?
The herbs that have more often interactions with medications are grapefruit and St John’s Wort.
Should herbs and supplements be taken before surgery?
The consumption of herbs and supplements should be stopped one month before surgery.
Can vitamins and minerals cause interactions with herbs, dietary supplements, medications, food, and alcohol?
Vitamins and minerals can cause interactions with herbs, dietary supplements, medications, food, and alcohol. For example, Vitamin E can inhibit platelet aggregation and antagonize vitamin K-dependent clotting factors. As a result, taking large doses of anticoagulants (blood thinners) or antiplatelet medications, such as warfarin (Coumadin (R)), can increase the risk of bleeding, especially in conjunction with low vitamin K intake (a vitamin essential for clotting). The amounts of supplemental vitamin E needed to produce clinically significant effects are unknown but probably exceed 400 IU per day.
Zinc is a mineral that can be harmful at a dose of 80 mg, so people should be sure to take this combination only under their doctor’s supervision. Zinc can cause copper deficiency, so a small amount of copper is added to the nutrients. In the AREDS I study for age-related macular degeneration, 7.5 percent of people who took zinc had problems, including urinary tract infections (UTIs), enlarged prostate, and kidney stones, compared to 5 percent of the people in the study who did not receive zinc.
Which are the medications that interact with most herbs and many dietary supplements?
The medications that interact with most herbs and many dietary supplements are the blood-thinners, especially warfarin. Some drugs that slow blood clotting include ardeparin, acetylsalicylic acid (aspirin), clopidogrel (Plavix®), diclofenac (Voltaren®, Cataflam®, etc.), dipyridamole, ibuprofen, naproxen, and other NSAIDs, dalteparin, enoxaparin, heparin, ticlopidine, warfarin (Coumadin®), dabigatran (Pradaxa®), rivaroxaban (Xarelto®), etc. Some drugs, such as aspirin and clopidogrel, are antiplatelets, while others, such as Warfarin (Coumadin®), dabigatran (Pradaxa®), rivaroxaban (Xarelto®), are blood-thinners.
Some herbs, such as turmeric (curcumin) and Ginkgo Biloba, and dietary supplements, such as vinpocetine, may slow blood clotting. Taking them along with blood-thinner medications that also slow clotting may increase the chances of bruising and bleeding.
When is the action of blood thinners lowered, then where may bleeding occur?
When the action of blood thinners is lowered, then bleeding may occur everywhere. It may be intracranially related to the brain vessels that cause stroke, especially if preexisting arteriovenous malformation or aneurysm. It may also be gastrointestinal, especially gastric (related to the stomach), or duodenal, especially if a pre-existing peptic ulcer. Other rarer sites include intra-ocular (inside the eye), post-peritoneal (often around the kidneys), vaginal (usually related to clotting defects), etc.
Can herbs decrease the blood-thinning effects of blood thinners?
Some herbs, such as soy, can decrease the effects of blood thinners, something that may lead to an increased risk of thrombosis! Also, green vegetables that contain vitamin K may reduce the effectiveness of the above medications and lower the INR. Some colleagues recommend against taking them, but as green vegetables are beneficial for circulation, a better approach is to consume daily a standard proportion and titrate the INR to the desirable levels, but not to take them at the same time with a blood thinner.
Which herbs increase bleeding tendency?
The herb that decreases the action of blood thinners may increase bleeding diathesis (tendency). Some examples are vitamin E, Ginkgo biloba, ginseng, dong quai, devil’s claw, feverfew, glucosamine, chondroitin, ginger, garlic, and fish oil (omega-3 fatty acids).
Are there interactions not well studied?
The interactions of many, if not most, herbs and supplements are not well studied. For instance, Arnica montana is an herb used topically for a wide range of conditions, including bruises, sprains, muscle aches, joint pain, etc. However, this herb might slow blood clotting and, thus, may interact with warfarin (a blood thinner) and alter the INR/PT increasing the bleeding diathesis (tendency). Therefore, there are concerns that it may interact with blood thinners/ antiplatelet/ anticoagulant medications, including aspirin, warfarin, and clopidogrel. But this concern is only theoretical as if applied topically (e.g., as joint cream), then a low dose is absorbed, so there is less chance of this interaction occurring.
Saffron is another example of potential interaction. Studies show that it might also slow blood clotting and, thus, it may also interact with warfarin. However, there are not any specific studies that investigated this interaction. This herb may also modify biochemical parameters that imply that it may affect, for example, the kidneys’ function.
Bilberry is an herb with many benefits with a potent antioxidant role that may prevent various medical problems, including eye disease. It may also interact with anticoagulants (blood-thinning medications). In theory, because the anthocyanosides antioxidants in bilberry may stop blood from clotting, there may be an increased risk of bleeding if bilberry is taken with blood-thinning medication, such as warfarin, and antiplatelets, such as aspirin. However, these concerns are theoretical.
Are there interactions that may be beneficial?
Some interactions of herbs or supplements may be beneficial. An example is the Coenzyme Q10 (CoQ10), a substance that is found naturally in the body and helps convert food into energy. Coenzyme Q10 is found in almost every cell in the body, and it is a powerful antioxidant. People with high cholesterol tend to have lower levels of coenzyme Q10, so coenzyme Q10 has been proposed as a treatment for high cholesterol, but there is no evidence of whether it works. There is some evidence it may reduce adverse reactions from conventional treatment with cholesterol-lowering drugs called ‘statins,’ which reduce natural levels of coenzyme Q10 in the body. Taking coenzyme Q10 supplements can bring levels back to normal. Additionally, studies show that coenzyme Q10 may decrease the muscle pain associated with statin treatment.
Are all the forms of an herb safe?
Not all herbal forms are safe. For instance, the roasted seed or crude Ginkgo biloba plant is possibly unsafe when taken by mouth. Eating more than ten roasted seeds per day can cause difficulty breathing, a weak pulse, seizures, loss of consciousness, and shock. Fresh seed is dangerous. Fresh seeds are poisonous, and eating them could cause seizures and death.
Another example is the Acai berry. Drinking raw acai juice has been linked to outbreaks of a disease called American trypanosomiasis (Chagas Disease). This parasitic disease, occurring mainly in South America, may cause serious heart problems.
Are manufactured (like pills, tablets, soft gels, etc.) herbs and dietary supplements safe? Can they contain adulterants or unknown contaminants? Is there also a concern about heavy metals?
There are concerns that manufactured (like pills, tablets, soft gels, etc.) herbs and dietary supplements may contain adulterants, i.e., unlabeled substances or unknown contaminants. These may be noxious. Another issue is that they may not provide the concentration of the herb or dietary supplement, or their active substance, in adequate amounts for treatment, meaning that their efficacy is sub-potent. Other concerns are adverse reactions and safety issues.
Importantly, herbs and supplements are not regulated by official organizations such as the FDA (Food and Drug Administration), so there are concerns about their efficacy and safety.
For example, a case report described a patient who developed rhabdomyolysis temporally associated with the use of a mislabeled acai berry dietary supplement. Assessment using the Naranjo Adverse Drug Reaction Probability Scale yielded a score of 3, indicating a possible relationship between the supplement and rhabdomyolysis. Although the product was labeled and promoted as containing acai berry and additional ingredients, no acai berry was found in the analysis. In conclusion, therapists should be aware that all dietary supplements may vary in uniformity and contain unknown contaminants.
Scutellaria lateriflora (American skullcap) is an herb used as an ingredient in numerous herbal products. However, it has been occasionally adulterated and contaminated with Teucrium canadense and T. chamaedrys, commonly known as germander, which contains hepatotoxic (toxic to the liver) substances called diterpenes.
Another example is Salvia divinorum. Laboratory analysis was conducted to determine the content of the hallucinogen psychoactive terpenoid salvinorin A in a variety of Salvia divinorum herbal products and to compare the content with the label claims of potency and purity. Hallucinogen is a substance that induces experiences that are qualitatively different from those of ordinary consciousness, often compared to non-ordinary forms of consciousness such as trance, meditation, and dream. Five herbal products containing Salvia divinorum were included as samples. The study concluded that the five salvinorin herbal products were found to be sub-potent, and three products contained adulterants. The study refers to the fact that any discrepancy between the advertised salvinorin A concentration and their actual level may pose a potential risk of both misuse and overdose. These concerns and the recently reported teenage suicide that could have been related to salvia consumption underscore the need for practitioners to become familiar with the signs and symptoms of salvia use.
Red yeast rice is a supplement that has been criticized for ‘adultery!’ Studies have shown that red yeast rice contains substances that are like prescription ‘statin’ cholesterol-lowering medications. One of these substances, called monacolin K, has the same makeup as the ‘statin’ drug lovastatin. Statins are prescribed to lower LDL cholesterol (‘bad’ cholesterol) levels and help to reduce the risk of heart disease. Researchers are not sure if the cholesterol-lowering effect of red yeast rice is due to the presence of lovastatin or other compounds in red yeast rice. However, because many red yeast rice supplements did contain lovastatin, the US FDA (Food and Drug Administration) considered them drugs, not supplements, and required manufacturers to remove any red yeast rice products that contained lovastatin from the market.
Herbs and dietary supplements may also contain heavy metals and toxins. For example, omega-3 fatty acids EPA and DHA are included in fish oil. Some fish may contain potentially harmful contaminants, such as heavy metals (including mercury), dioxins, and polychlorinated biphenyls (PCBs). Some fish meats (especially shark, king mackerel, and farm-raised salmon) can be contaminated with mercury and other industrial and environmental chemicals.
May manufactured herbs and supplements be mislabeled?
All dietary supplements may vary in uniformity and contain unknown contaminants! Studies from the FDA and other drug organizations have revealed that some manufactured herbs and dietary supplements were mislabeled. They contained different (usually lower) doses than the label informed or did not contain at all the active substance they claimed to. They also contained ''adulterants'' that were often harmful such as toxins or even drugs that ensured that would achieve the desired effects. For instance, some red yeast rice supplements contain a statin (a drug that decreases cholesterol) to ensure their cholesterol-lowering result! This drug also has side effects such as liver and muscle toxicity. The latter may be life-threatening.
A case report described a patient who developed rhabdomyolysis temporally associated with the use of a mislabeled acai berry dietary supplement. Assessment using the Naranjo Adverse Drug Reaction Probability Scale yielded a score of 3, indicating a possible relationship between the supplement and rhabdomyolysis. Although the product was labeled and promoted as containing acai berry and additional ingredients, no acai berry was found on analysis!
A 2015 analysis of twenty-three brands of vinpocetine dietary supplements revealed reported labeling errors. Only 26 percent of the labels stated accurate dosages of vinpocetine, while 26 percent contained no vinpocetine at all! Overall, 39 percent of the products tested were mislabeled, and 74 percent did not provide information on the quantity of vinpocetine. A 2016 investigation of eight brands of vinpocetine supplements sold in the USA discovered that the amount of vinpocetine contained was highly variable!
Should the consumer prefer well-known manufacturers and purchase from reputable sites?
To my mind, it is safer for consumers to purchase herbs and dietary supplements from reputable companies with various products. Otherwise, standards are low, and possibly the supplement is imported as a powder from China, the most polluted country on the planet. Many sites, including eBay and Amazon, facilitate
consumer-to-consumer and business-to-consumer sales through their website.
Consumers should prefer an e-shop as a retailer rather than an anonymous seller. They should also avoid purchasing supplements from unknown manufacturers in a simple unlabeled plastic container without a trademark. Well-known manufacturers have better ISO standards and perform quality control, including the detection of toxic contaminants. At least, they ought to! If a pharmaceutical company also produces a product, it is preferable, as the standards are higher.
Many pharmaceutical companies manufacture products with herbs and supplements. For instance, Omacor® is a famous fish oil supplement produced by Abbot. Also notable are the formulas Ocuvite® Lutein forte/complete/ premium for treating age-related macular degeneration (AMD). They are based on AREDS studies and are produced by Bausch & Lomb.
Are GMOs safe?
Some herbs, such as soy, may be Genetically Modified Organisms (GMOs). There is no substantiated evidence that GMO foods are less safe than non-GMO-derived food products. Organic products should be preferred, e.g., spirulina, berries, etc.
Are manufactured (like pills, tablets, soft gels, etc.) herbs and dietary supplements better than natural ones? Are herb extracts better than pure natural herbs?
Whether or not manufactured (like pills, tablets, soft gels, etc.) herbs and dietary supplements are better than natural ones depends on how reliable the manufacturers are. Some studies showed that manufactured herbs or nutritional supplements contained a negligible amount of the labeled herb or dietary supplement, while others contained even ‘adulterants,’ additional unlabeled substances that may be dangerous or unknown contaminants
On the other hand, natural uncultivated herbs may be difficult to harvest in nature unless collected by an expert such as an herbalist. Not all herbs are easy to cultivate; many require specific weather and soil conditions, while others, such as Arnica, prefer a high altitude. Herb extracts contain a higher concentration of herbs than natural herbs. They may be made from parts of the herb (such as leaves, flowers, berries, etc.). These extracts may be produced naturally or manufactured.
The manufactured extracts are standardized to contain a specific amount of the herb that is mentioned on the label. However, it is doubtful if the ingredients that are listed are officially checked, as they are not regulated by official organizations such as the FDA (Food and Drug Administration). Thus, a consumer may trust a well-known company, but the manufactured herbs and dietary supplements are still not regulated similarly to medications.
There are official certifications such as ISO (an international standardization organization) for accrediting product quality. Moreover, organic natural herbs (such as spirulina, chlorella, soy, and berries) are safer, as they are deprived of pesticides, fertilizers, and polluters (including dioxins), while some companies sell non-GMO (genetically modified organism) forms such as soy or lecithin powder.
Do the companies that sell herbs and dietary supplements conduct or sponsor scientific investigations? Generally, does the interest in herbs and nutritional supplements promote research to make new substances (based on the original) with better absorption and better bioavailability?
The increased interest in herbs and dietary supplements promotes research to make new substances (based on the original) with better absorption and better bioavailability. A fitting example is curcumin, a yellow pigment of the spice turmeric that is being studied in cancer prevention, osteoarthritis, ulcerative colitis (UC), anterior uveitis, Alzheimer’s Disease (AD), and other medical problems. In India, which consumes elevated levels of curcumin in curry, the incidence of Alzheimer’s disease is significantly lower than in other countries. Unfortunately, curcumin exhibits low oral bioavailability in rodents and humans, i.e., low levels in plasma and tissues. Potential factors limiting curcumin's bioavailability include poor absorption, rapid metabolism, and rapid systemic elimination. Numerous approaches to increasing curcumin bioavailability have been explored, including the use of adjuvants like piperine, which interfere with glucuronidation; liposomal curcumin; nanoparticles; curcumin phospholipid complexes; and structural analogs of curcumin.
A product with enhanced absorption is Meriva®, a proprietary complex of curcumin with soy phosphatidylcholine. Studies showed that Meriva decreased joint pain and improved joint function in osteoarthritis (OA) patients. Longvida® is a manufactured bioavailable formulation of solid lipid curcumin particle (SLCPTM) technology that is especially useful for Alzheimer’s disease (AD).
Another product with enhanced absorption is bio-curcumin-conjugated nanoliposomes with curcumin exposed at the surface were designed. A study concluded that curcumin-conjugated nanoliposomes could be applied to diagnose and target drug delivery in Alzheimer’s disease (AD).
Curcumin was encapsulated in a biodegradable poly (lactide-co-glycolide) (PLGA) based-nanoparticulate formulation in another study. The results of the study demonstrated that this formulation could be a promising drug delivery strategy to protect neurons against oxidative damage, as observed in Alzheimer's disease (AD).
Regarding lutein, a carotenoid used for the prevention of age-related macular degeneration (AMD), the manufactured patented form FloraGlo® exhibits enhanced bioavailability. However, it is not contained in popular products such as the ones from Ocuvite®.
Are there safety concerns related to the fact that herbs and dietary supplements are regulated and manufactured with no uniform standards?
Safety concerns have been raised as herbs and dietary supplements are regulated and manufactured with no uniform standards. For instance, the Alzheimer’s Disease Cooperative Study (ADCS) that investigated huperzine A as a treatment for mild to moderate Alzheimer’s disease found that currently available formulations of huperzine A are dietary supplements that are unregulated and manufactured with no uniform standards. According to the study, taking these unregulated preparations could increase the risks of severe adverse reactions, especially if used in combination with FDA-approved Alzheimer's drugs.
Is there a rivalry between conventional and complementary medicine that affects research in herbs and supplements?
From my point of view, there is a rivalry between conventional and complementary medicine, meaning that there is a conflict of interest between researchers sponsored by drug companies to degrade the benefits of herbs and dietary supplements as they are natural and cannot be patented as drugs. However, many pharmaceutical companies manufacture forms with herbs and supplements. For instance, Omacor® is a famous fish oil supplement produced by a drug company. Drug and biotechnology manufacturers also investigate bioavailable forms of natural substances and their active ingredients that may be patented, such as Meriva®, a bioavailable form of curcumin. Also famous are the formulas Ocuvite® Lutein forte/complete/ premium for treating age-related macular degeneration (AMD). Regarding lutein (a carotenoid used for the prevention of AMD), the manufactured patented form FloraGlo® exhibits enhanced bioavailability. However, it is not contained in the Ocuvite® products.
Are herbs & supplements manufactured by pharmaceutical companies safer?
Many pharmaceutical companies manufacture products with herbs and supplements. For instance, Omacor® is a famous fish oil supplement produced by Abbot. Also notable are the formulas Ocuvite® Lutein forte/complete/ premium for treating age-related macular degeneration (AMD). They are based on AREDS studies and are produced by Bausch & Lomb.
Well-known pharmaceutical companies have high standards and, from my perspective, are safer than the exclusive herb and supplement manufacturers. Fundamental is the issue of quality control for herbs and supplements, including their origin. For instance, if the ingredients are imported as a powder from China, we should keep in mind that safety concerns are raised as this is the most polluted country on the planet! On the other hand, we should be skeptical about pharmaceutical companies that, for a lower cost reason, have industries in countries of dubious quality control, such as India and China.
Should people stop taking conventional medications and replace them with herbs and dietary supplements?
As a medic, I discourage the replacement of conventional medical treatment with herbs and dietary supplements, as this may have harmful, even deadly, health effects. However, these can be taken in combination with medications under medical supervision. That is why we call this medicine ‘complementary.’ However, adverse reactions, contraindications, and interactions should be taken into consideration, and the appropriate to do this is not an herbalist or a naturopath but a medical professional. For instance, a patient with Alzheimer’s disease who takes a medication called anticholinesterase inhibitors may enhance their effects by taking concomitantly the herb huperzine A which has similar actions, and this may increase the risk of adverse reactions, including bradycardia (slow heartbeat).
Should a patient stop conventional cancer treatment and replace it with an herb or a dietary supplement with unknown efficacy?
As a medic, I believe that cancer should be treated only with conventional medications. It should never be treated with alternative therapies alone. But, if someone chooses to use complementary therapies along with medical treatment of cancer, he/she should speak with his/her oncologist about this as herbs and supplements have specific indications, contraindications, adverse reactions, and interactions with other drugs. Their combination with anti-cancer drugs may increase the risk of these adverse reactions, including bleeding tendency. A patient who chooses to take inclusively complementary medicine for cancer will do it with his/her responsibility regardless of the recommendation against this practice. Of course, all these do not mean that many herbs and supplements are deprived of anticancer effects. However, these are under investigation.
A significant issue is that even if an herb or a supplement has potent anticancer effects. Indeed, the concentration that an individual would need to consume would be far higher than the existing manufactured formulas.
Should herbs and dietary supplements be used under medical supervision?
Herbs and dietary supplements should be used under medical supervision (not just by an herbalist) and should be taken only as a complementary treatment, as there are concerns about their efficacy and safety.
We should all keep in mind that herbs and dietary supplements have specific indications, contraindications, interactions with other drugs, and adverse reactions. Also, in many medical conditions, their efficacy is questioned.
Are there herbs and dietary supplements whose efficacy is well studied?
There are many herbs and dietary supplements with well-studied efficacy. An example is natural supplements for treating age-related macular degeneration (AMD), a condition affecting the central area of the retina (the back of the eye). The retina can deteriorate with age, and some people get lesions that can lead to losing central vision. The National Eye Institute’s Age-Related Eye Disease Study (AREDS) found that taking a specific high-dose formula of antioxidants (vitamin C, vitamin E, and beta-carotene) and zinc may delay or prevent intermediate age-related macular degeneration from progressing to the advanced stage. The study revealed some problems, such as the fact that 7.5 percent of people who took zinc had issues including urinary tract infections, enlarged prostate, and kidney stones, compared to 5 percent of the people in the study who did not receive zinc.
The AREDS 2 study was conducted to overcome this problem. The primary purpose of the Age-Related Eye Disease Study 2 (AREDS2) was to evaluate the efficacy and safety of lutein plus zeaxanthin (L+Z) and/or omega-3 long-chain polyunsaturated fatty acid (LCPUFA) (fish oil) supplementation in reducing the risk of developing advanced AMD. The study also assessed the reduction in zinc and the omission of beta-carotene from the original AREDS formulation. The study reported no overall benefit from adding omega-3 fatty acids or lutein and zeaxanthin to the formulation. However, the study found benefits in two subgroups of participants: those not given beta-carotene and those with little lutein and zeaxanthin in their diets. Removing beta-carotene did not restrain the formulation's protective effect against developing advanced AMD. That is important, as high doses of beta-carotene have been linked to a higher risk of lung cancer in smokers
Another example of well-studied dietary supplements is the omega-3 fatty acids (EPA and DHA) that come from fish oil. Fish oil can have a therapeutic role in the treatment of marked hypertriglyceridemia (high blood triglycerides). Omega-3 fatty acids are beneficial for the heart, and their beneficial effects include anti-inflammatory and anti-blood clotting actions, lowering cholesterol and triglyceride levels, and reducing blood pressure. These fatty acids may also reduce the risks and symptoms of other disorders, including diabetes, stroke, rheumatoid arthritis, asthma, inflammatory bowel disease, ulcerative colitis, some cancers, and mental decline. However, studies are not conclusive if fish oil helps with all the above conditions, except high blood triglycerides. There are also studies about their beneficial role in the prevention of Age-related macular degeneration (AMD) included in the AREDS2 study, as mentioned above.
Is there confusion about the nomenclature of some herbs?
For some herbs, there is confusion about their common name. For example, blueberries sometimes are confused with bilberries. Outside of the USA, the name ‘blueberry’ may be used for the plant ‘bilberry’ in the USA. Since most people in the world refer to ‘blueberries,’ no matter if they mean the European blueberry Vaccinium myrtillus (bilberry) or the American blueberry, there is a lot of confusion about the two identical fruits worldwide. Some differences distinguish bilberries or European blueberries from their American counterpart. One of the differences is that bilberries are wild plants, while American blueberries can be cultivated.
Another example is the adaptogen herb ‘Eleuthero’, which sometimes is wrongly called ‘Siberian Ginseng’ (Eleutherococcus senticosus). The latter belongs to the same family but is not the same genus as the true Ginseng. Panax Ginseng is considered to be an adaptogenic herb. The active compounds in Eleuthero are eleutherosides, while in Panax ginseng are ginsenosides.
Is there a reliable dosage for herbs and dietary supplements?
Often there is no reliable dosage for herbs and dietary supplements. Exceptions are few, such as for fish oil (containing omega-3 fatty acids) for specific indications such as high blood triglycerides. The proper dosage for most herbs and dietary supplements hasn’t been established yet but varies. On MedlinePlus ( http://www.nlm.nih.gov/medlineplus/ ), the National Center for Complementary and Integrative Health ( https://nccih.nih.gov/ ), and the University of Maryland Medical Center ( http://www.umm.edu ) on some herbs and dietary supplements, the doses (most of them for adults only) are mentioned and are based on scientific research. However, there are no ‘official’ doses for most herbs and nutritional supplements, such as the doses of a medication referred to in the national formula (such as the BNF; British national formula) or the FDA’s guidelines.
Is there an optimal and sub-optimal dosage for herbs and dietary supplements?
An optimal dosage for herbs and dietary supplements is needed to exhibit therapeutic properties. Otherwise, the dose may be sub-optimal, and the consumed herb or supplement will not be beneficial. For instance, fish oil (that contains omega-3 fatty acids EPA and DHA) helps (e.g., in reducing triglycerides) on daily doses of at least 1 gram, although the recent trend is to focus on the EPA and DEA concentration.
The doses are different for the specific indications that they apply. For example, the recommended dosage of fish oil will be different if taken for high triglycerides, for high blood pressure (hypertension), for reducing the overall risk of death in patients with coronary heart disease (CHD), and for preventing and reversing the progression of hardening of the arteries (arteriosclerosis).
In many cases, an optimal dose has not been defined. For instance, for CoQ10 (Coenzyme Q10) taken for cardiovascular diseases, the ‘recommended’ dosage varies between 50 and 200 mg per day.
An example in which the optimal dose is essential is the phytosterols (plant sterols). The National Cholesterol Education Program recommends consuming 2 grams of plant sterols/stanols every day as part of an overall heart-healthy diet. A daily intake of about 2 grams of either stanols or sterols reduces LDL cholesterol (‘bad’ cholesterol) by roughly 5–15 percent, often within weeks. Unfortunately, many formulas contain less than the recommended dose of phytosterols. Some companies use beta-sitosterol, while others prefer beta-glucans (contained in oats) that also have cholesterol-lowering properties.
Many manufactured products (especially multivitamins) contain sub-optimal doses of dietary supplements and herbs. That means that the amount they provide is so low that it is not expected to have therapeutic properties.
Can all herbs be taken orally (by mouth)?
Not all herbs are taken orally (by mouth). For example, people should not take the herb arnica (used, e.g., for arthritis) by mouth except under the close supervision of a doctor. Homeopathic remedies, which use minimal amounts of arnica, can usually be taken safely.
Also, taking Aloe vera latex by mouth (orally) may cause severe intestinal cramps or diarrhea and is not recommended.
The FDA does NOT approve dietary supplements!
The FDA (Food and Drug Administration of the USA) webpage states, ''Unlike new drugs, dietary supplements are NOT reviewed and approved by FDA based on their safety and effectiveness. Unless an exception applies, dietary supplements that contain a new dietary ingredient (a dietary ingredient not marketed in the United States before Oct. 15, 1994) require a notification to FDA at least 75 days before marketing.'' (Reference: https://www.fda.gov/consumers/consumer-updates/it-really-fda-approved Retrieved: 17 September 2021)
The importance of FDA approval and the need for Quality Control & ISO standards
Safety concerns raise the importance of quality control on herbs and supplements by independent agencies. These products must be regulated and approved by national drug organizations, including the FDA (the U.S. Food and Drug Administration). A vigilance from these agencies for mislabeling, harmful concomitants, and adverse reactions is also necessary. Currently, drug organizations do not approve herbs and supplements. They do not monitor them but investigate only a small sample of the herb & supplement manufacturers or intervene after an official complaint. However, herb & supplement approval and monitoring should occur for all companies, not a minority, for the consumers' safety. Private organizations can also perform quality control. Manufacturers should be obligated to adhere to ISO standards for their products' quality, safety, and compliance.
Should people consult a medical practitioner before taking any herb or dietary supplement?
Taking an herb or a dietary supplement is not always safe unless guided by an herbalist, although, ideally, complementary medicine should be a medical subspecialty. But it is not. A medical professional can handle the treatment with herbs and supplements as they have specific indications, contraindications, adverse reactions, as well as interactions with other drugs. Their combination with medications may increase the risk of these adverse reactions, including bleeding tendency.
Special groups (such as children, pregnant and breastfeeding women, older adults, and patients) need to consult their doctor before taking an herb or a supplement. Presuming that an herb is natural and safe is misleading as often both attributions can be questioned.
From my experience, many people take herbs or supplements without consulting a medical practitioner, exposing themselves to potentially adverse effects. Naively, their only ‘guidance’ is the advertisement or commercial of the manufacturer! An example is the herb ‘Echinacea’, which is advertised as an ‘immune booster’ for the common cold and flu. The concern is if the dose of the product is optimal to help, as well as the fact that this herb is contraindicated to be taken for more than 7-10 days, while it is not prudent to be taken prophylactically to prevent flu, as some do!
The author’s recommendations
Regarding all these safety issues, I recommend purchasing herbs and dietary supplements from reputable companies with a variety of products. Otherwise, standards are low, and possibly the supplement is imported as a powder from China, the most polluted country on the planet. Many sites, including eBay and Amazon, facilitate consumer-to-consumer and business-to-consumer sales through their website. You should prefer an e-shop as a retailer rather than an anonymous seller. You should also avoid purchasing supplements from unknown manufacturers in a simple unlabeled plastic container without a trademark. Well-known manufacturers have better ISO standards and perform quality control, including the detection of toxic contaminants. At least, they ought to!
If a pharmaceutical company also produces a product, it is preferable, as the standards are higher. Many pharmaceutical companies manufacture products with herbs and supplements. For instance, Omacor® is a famous fish oil supplement produced by Abbot. Also notable are the formulas Ocuvite® Lutein forte/complete/ premium for treating age-related macular degeneration (AMD). They are based on AREDS studies and are produced by Bausch & Lomb.
Additionally, you should prefer, if available, organic forms of herbs (such as spirulina, vegetables, and berries) and herbs and supplement products certified as not containing harmful substances, such as fish oils deprived of heavy metals. For this reason, you should check the label and their site if they have such certification or ISO. Regarding Genetically Modified Organisms (GMOs), there is no substantiated evidence that GMO foods are less safe than non-GMO-derived food products. In any case, organic products should be preferred.
Epilogue
Everything considered, herbs and supplements are not a panacea. They do not treat everything and may not be appropriate or suitable for everyone. Of extreme importance is the quality control by independent agencies and the regulation and approval, as well as vigilance, by national drug organizations, including the FDA.
To put it briefly, SAFETY should come first!
Thanks for reading!
