Food, Herbs & Supplements

Biotin, also known as vitamin B7, is a water-soluble vitamin that is widely recognized for its purported benefits in promoting healthy hair, skin, and nails. However, the evidence supporting its efficacy for these purposes remains inconclusive. While a deficiency in biotin can lead to hair loss, skin issues, and brittle nails, most individuals obtain sufficient biotin through their diet, which includes foods like beef liver, eggs, salmon, avocados, sweet potatoes, and seeds. Certain groups, such as individuals with alcohol dependence and women who are pregnant or breastfeeding, may require additional biotin supplementation.

Biotin plays a crucial role in several metabolic processes. It helps enzymes in breaking down fats, carbohydrates, and proteins, and it regulates cell signaling and gene activity. This essential nutrient is naturally present in many foods and is available as a dietary supplement. Despite its popularity, there is no Recommended Daily Allowance (RDA) for biotin due to insufficient evidence supporting a specific daily requirement for healthy individuals. The average recommended amount for adults is 30 micrograms per day.

Biotin’s role in enzyme function is critical. It acts as a cofactor for five carboxylases: propionyl-CoA carboxylase, pyruvate carboxylase, methylcrotonyl-CoA carboxylase, acetyl-CoA carboxylase 1, and acetyl-CoA carboxylase 2. These enzymes are involved in the metabolism of fatty acids, glucose, and amino acids, highlighting biotin’s importance in maintaining metabolic health. The nutrient also contributes to the formation of fatty acids, which nourish the skin, suggesting a possible mechanism for its perceived benefits in skin health.

Despite its essential role in the body, there is a lack of robust scientific evidence to support the widespread use of biotin supplements for improving hair, skin, and nails. Several small studies and case reports have suggested benefits, but these studies often have significant design flaws, such as the lack of a placebo group and unclear baseline biotin status of participants. Reports of hair growth benefits are primarily anecdotal and often involve children, further emphasizing the need for more rigorous research.

One of the concerns with high biotin intake is its potential to interfere with diagnostic tests. Excessive biotin can affect assays that use biotin-streptavidin technology, commonly employed to measure hormone levels, including thyroid hormones. This interference can result in falsely normal or abnormal results, leading to misdiagnoses of conditions like Graves' disease and severe hyperthyroidism. The FDA has issued warnings about this issue, noting that biotin levels nearly 600 times the RDA can cause such interference. Recent case reports have described instances of false indications of Graves' disease and severe hyperthyroidism in patients taking 10-300 mg of biotin per day.

Biotin can also interact with certain medications. For example, anticonvulsant treatments for epilepsy have been associated with lower serum biotin levels, likely due to increased biotin catabolism and reduced intestinal absorption. Medications such as carbamazepine, primidone, and phenobarbital can increase the metabolism of biotin, leading to a deficiency in some individuals.

In conclusion, while biotin is an essential nutrient for various metabolic processes and overall health, its use for enhancing hair, skin, and nails is not strongly supported by scientific evidence. The nutrient’s role in metabolic conversions, including fatty acid formation, contributes to its perceived benefits for skin health. However, caution is advised when using biotin supplements, considering their potential to affect diagnostic tests and interact with certain medications. Future research is needed to provide more definitive answers regarding biotin’s efficacy and safety, particularly in high doses. Until then, individuals should aim to meet their biotin needs through a balanced diet, reserving supplements for those with a demonstrated deficiency or specific medical conditions that warrant additional biotin intake.

Zempleni, J., Wijeratne, S.S.K. and Hassan, Y.I. (2009), Biotin. BioFactors, 35: 36-46. https://doi.org/10.1002/biof.8

Patel, D. P., Swink, S. M., & Castelo-Soccio, L. (2017). A Review of the Use of Biotin for Hair Loss. Skin appendage disorders, 3(3), 166–169. https://doi.org/10.1159/000462981

Vitamin B7, commonly known as biotin, is a supplement that aids in converting carbohydrates, fats, and proteins into energy. This water-soluble vitamin is a cofactor for five carboxylases: propionyl-CoA carboxylase, pyruvate carboxylase, methylcrotonyl-CoA carboxylase, acetyl-CoA carboxylase 1, and acetyl-CoA carboxylase 2. These carboxylases catalyze the metabolism of fatty acids, glucose, and amino acids. The amount of biotin needed is based on age. For adults like myself, 30 mcg is the average daily recommended amount. Biotin can be found in our everyday foods such as meat (primarily organ meats), fish, eggs, seeds, nuts, and even vegetables like spinach and broccoli. For people unable to meet the recommended amount through their diet, dietary supplements are available to fulfill this requirement. Those with alcohol dependence and who are pregnant or breastfeeding are more likely to be low on biotin. The importance of getting enough biotin is due to its symptomatic effects. Biotin deficiency may cause hair thinning, hair loss, brittle nails, weakness, and increased susceptibility to skin infections and damage. There is no significant harm in receiving biotin above the recommended limit. The only thing to keep in mind is the potential of creating false lab readings. 

Many supplements contain combinations of B-complex vitamins, as do many multivitamins. The exact amount of intake is reported on the back label of products and should be examined. Many products are advertised as “hair, skin, and nail” supplements to attract certain demographics. Unfortunately, these products are not FDA-approved. Users may notice on the product it states, “Produced in an FDA-approved facility”. This does not correlate to the products being efficient. Many articles have been written to support the use of biotin supplements and showcase their efficacy. However, no trials have been conducted showing successful cases of preventative hair loss or strengthened nails, etc.

In 2019, the FDA issued a follow-up statement regarding biotin’s interference in test results. No other statements have been produced. It has newly been discovered that excess biotin levels may result in incorrect troponin levels. The FDA has been involved with manufacturers to mitigate these issues. However, such faulty values are seen in biotin levels nearly 600 times the recommended dietary allowance (RDA). 

Although the exact mechanism of biotin has not been formally established, many hypotheses suggest its role in the Kreb Cycle assists in skin benefits. The formation of fatty acids is what nourishes the skin. Biotin takes part in various metabolic chemical conversions, which is primarily where its role comes from. Biotin is a key component in a healthy diet to maintain one’s skin and health.

References

1. https://www.webmd.com/vitamins/ai/ingredientmono-313/biotin

2. https://ods.od.nih.gov/factsheets/Biotin-Consumer/

3. https://ods.od.nih.gov/factsheets/Biotin-HealthProfessional/

4. https://www.hsph.harvard.edu/nutritionsource/biotin-vitamin-b7/#:~:text=It%20is%20a%20water%2Dsoluble,and%20the%20activity%20of%20genes.%20%5B

Common Name/Scientific Name:

            There are two primary species of cranberry: the American cranberry, scientifically known as Vaccinium macrocarpon, and the European cranberry, known as Vaccinium oxycoccos.

What is it used for?

            Cranberries are referred to as a superfood because of their rich nutrient and antioxidant profile, especially in terms of flavonoids and polyphenols. They are known to reduce the likelihood of urinary tract infections, offer potential protection against certain cancers, boost immune function, and help lower blood pressure.

How does it work?

            The abundance of antioxidant proanthocyanidins (PACs) in cranberries can potentially hinder certain bacteria from adhering to the urinary tract walls, thus aiding in infection prevention. However, a concentrated cranberry extract is typically needed to achieve this effect, as commercially available cranberry juices do not contain sufficiently high levels of PACs. Moreover, these PACs may also promote oral health by protecting teeth against a specific bacteria strain that contributes to tooth decay and by preventing gum disease.

            The antioxidants found in cranberries might enhance heart health by lowering the risk of cardiovascular disease. These antioxidants also possess anti-inflammatory properties, which could help diminish overall inflammation in the body and alleviate symptoms of conditions like arthritis. Furthermore, they may reduce LDL (bad) cholesterol levels while boosting HDL (good) cholesterol levels. Some research suggests that cranberry antioxidants could even play a role in preventing certain types of cancer such as breast, colon, prostate, and lung cancer by lessening oxidative stress and inflammation.

What are some side effects?

            Common side effects of cranberry consumption may include stomach upset, such as nausea, vomiting, or diarrhea, as well as an increased risk of kidney stones due to higher levels of oxalate in the urine. Allergic reactions are also possible. Additionally, individuals should be cautious about cranberry products with high sugar content, as they may impact blood sugar levels.

Are there any trials that support its use/non-use (efficacy)? Provide details.

            Clinical studies have shown that consuming cranberry juice or solids can effectively prevent UTIs in various populations, including women with recurrent UTIs, pregnant women, the elderly, and children. For example, a randomized, double-blind, placebo-controlled study involving women aged 28–44 years with recurring UTIs found that 70% of the subjects experienced fewer UTIs while taking 400 mg of cranberry solids daily for 3 months compared to those taking a placebo. Another study on women aged 25–70 years with a history of high UTI recurrence showed that consuming 200 mg of concentrated cranberry extract standardized to 30% phenolics twice a day for 12 weeks prevented UTI recurrence in all subjects for the study's duration. A follow-up study conducted 2 years later on these subjects found that those who continued to take cranberry remained free of infection.

Additional Considerations (Can include known drug interactions, special directions, etc.)

            Cranberries can interact with drugs like warfarin and other blood thinners, enhancing their anticlotting effects. Additionally, cranberries contain salicylic acid, so individuals who regularly take aspirin should avoid cranberry supplements or excessive cranberry juice consumption.

            It is not advisable to use cranberry products if you already have a urinary tract infection (UTI).

References:

Neto CC, Vinson JA. Cranberry. PubMed. Published 2011. https://www.ncbi.nlm.nih.gov/books/NBK92762/

Nemzer BV, Al-Taher F, Yashin A, Revelsky I, Yashin Y. Cranberry: Chemical Composition, Antioxidant Activity and Impact on Human Health: Overview. Molecules. 2022;27(5):1503. doi:https://doi.org/10.3390/molecules27051503

‌Cranberry Information | Mount Sinai - New York. Mount Sinai Health System. Published 2010. https://www.mountsinai.org/health-library/herb/cranberry

Common Name/Scientific Name: 

The name of this supplement is Omega-3 Polyunsaturated fatty acids. It is commonly referred to as fish oil. However, scientifically it can be classified to include α-linolenic acid, stearidonic acid,, eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid. 

What is it used for? 

Omega-3 polyunsaturated fatty acids can be used for a plethora of diseases. Omega-3 has been linked to improvements in diseases like cardiovascular disease, diabetes, cancer, Alzheimer’s disease and dementia, depression,  visual/neurological brain development, and lastly maternal and child health. Some of these diseases require further clinical investigation for the benefits of omega-3. 

Omega-3 is mostly known for its reduction of cardiovascular disease. This has been studied intently in many different clinical trials which I will name below. The American Heart Association (AHA) recommends that people with CHD or HF take 1,000mg of omega-3 supplements per day. Omega-3 has been linked to a lower risk of death in both men and women with CHD.  In 2017, the AHA based on new randomized clinical trials that were published “suggested that omega-3 supplementation did not provide any benefits toward preventing cardiovascular disease among patients with or at risk for diabetes mellitus and did not lower the risk of stroke among patients without a history of stroke (1)”.  Patients using Omega-3 supplementation should have a history of CVD as it does not help prevent cardiovascular disease but rather reduces the risk of mortality from the disease. 

How does it work? 

Omega-3 lowers triacylglycerol production as well as preventing arrhythmias and atherosclerosis. By reducing plasma triglyceride levels in the liver, it reduces the risk of cardiovascular disease. There are numerous mechanisms discussed as to how fish oil decreases plasma triglyceride levels. One of the mechanisms discussed is that “fish oil could activate transcription factors which control metabolic pathways in a tissue-specific manner regulating nutrient traffic and reducing plasma TG (2)”.  

What are some side effects?

Side effects of omega-3 supplements are usually mild. They include unpleasant taste, bad breath, bad-smelling sweat, headache, and gastrointestinal symptoms such as heartburn, nausea, and diarrhea (3). 

Are there any trials that support its use/non-use (efficacy)? Provide details.  

The landmark trial that introduced the benefits of Omega-3 supplements was GISSI-P. This trial showed that 1 g/day Ω-3 (EPA + DHA) decreased the risk of death, non-fatal acute MI, and stroke in patients with recent MI (<3 months) (4). Another trial was JELIS, which was studied in the Japanese population, and their diets from the beginning included fish, which is argued against a Western diet (American) that doesn’t include a lot of fish to begin with.  These studies were for the use of omega-3. However, in 2017, three different trials were published that negated the benefits of omega-3 supplementation. The OMEGA, ASCEND, and VITAL trials showed there was no reduction in CVD disease. Another trial, REDUCE-IT, published recently supported a 4g dose of omega-3 in reducing CVD risk and TG levels. 

Additional Considerations (Can include known drug interactions, special directions, etc.)

Fish oil can have antiplatelet effects at high doses, although it appears to be less potent than aspirin. We should inform patients who take medication like Warfarin and other strong anticlotting agents. Omega-3 can be found in a rich seafood diet. While one might worry about the mercury levels in their seafood, salmon, anchovies, sardines, pacific oysters, and trout are low in mercury and high in omega-3.

References:

1. Shahidi, F., & Ambigaipalan, P. (2018). Omega-3 Polyunsaturated Fatty Acids and Their Health Benefits. Annual review of food science and technology, 9, 345–381. https://doi.org/10.1146/annurev-food-111317-095850

   
   

2. Shearer, G. C., Savinova, O. V., & Harris, W. S. (2012). Fish oil -- how does it reduce plasma triglycerides?. Biochimica et biophysica acta, 1821(5), 843–851. https://doi.org/10.1016/j.bbalip.2011.10.011

   
   

3. https://www.nccih.nih.gov/health/omega3-supplements-in-depth#:~:text=Side%20effects%20of%20omega%2D3,higher%20risks%20of%20prostate%20cancer.

   
   

4. Elagizi, A., Lavie, C. J., O'Keefe, E., Marshall, K., O'Keefe, J. H., & Milani, R. V. (2021). An Update on Omega-3 Polyunsaturated Fatty Acids and Cardiovascular Health. Nutrients, 13(1), 204. https://doi.org/10.3390/nu13010204

   
   

BIOTIN

Common Name/Scientific Name:

The name of this supplement is called biotin and it is a B vitamin, vitamin B7. Its scientific name is called 5-[(3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl]pentanoic acid.

What is it used for?

Biotin supplements are often known for the treatment of hair loss. It promotes the increase of healthy hair skin and nails. However, a deficiency in biotin can lead to hair loss and skin and nail problems, evidence showing a benefit of supplementation is inconclusive. A small amount of case reports and small trials have shown a benefit but the study design overall was weak. Although there is a lack of evidence on the efficiency of biotin it is still very popular.

How does it work?

Biotin plays a vital role in assisting enzymes to break down fats, carbohydrates, and proteins in food. It also helps to regulate signals sent by cells and the activity of genes. It is and essential nutrient that is naturally present in some foods but also available as a dietary supplement. You can find biotin in foods such as, beef liver, eggs, salmon, avocados, sweet potatoes and seeds. Biotin is found in some multivitamins and minerals supplements, but it is also sold on its own. Most people get enough vitamin from the foods they already eat. However, certain groups of people may not which is rare. This includes people with alcohol dependance, as well as women who are pregnant and breastfeeding.

What are some side effects?

There was no evidence in humans that biotin is toxic at high intakes. However, very high intakes of biotin may interfere with diagnostic assays that use biotin- streptavidin technology and are commonly used to measure levels of hormones like thyroid hormones. It tends to give falsely normal or abnormal results. A few recent case reports have described finding false indication of Graves’ disease and severe hyperthyroidism in patients taking 10-300mg of biotin per day. Biotin can also interact with certain medications. In a study done for people with epilepsy, anticonvulsant treatments for at least one year was associated with very low serum biotin levels than in control group patients. These medications included carbamazepine, primidone and phenobarbital. Overall, the reason for this could be that anticonvulsant treatment increases biotin catabolism. This ultimately leads to reduced biotin status and inhibition of intestinal biotin absorption.

Are there any trials that support its use/non-use (efficacy)? Provide details.

Evidence on Biotin supplementation to treat brittle nails includes three smalls studies that had many flaws. The studies did not include a placebo group. Also the reports did not indicate any baseline biotin status of the participants. Reports about hair growth were also document in several case reports, however, they were all done in children. Overall, future studies are needed to determine whether biotin supplements might improve hair nails and skin.

Additional Considerations (Can include known drug interactions, special directions, etc.)

Overall, there is no Recommended daily allowance (RDA) for biotin because there is not enough evidence to support that a daily amount is needed in a healthy person. The popularity of Biotin promoting healthy hair skin and nails is more of a myth until further detailed testing is done with biotin.

Reference:

“Office of Dietary Supplements - Biotin.” NIH Office of Dietary Supplements, U.S. Department of Health and Human Services, ods.od.nih.gov/factsheets/Biotin-HealthProfessional/#h12. Accessed 25 Jan. 2024.

“Biotin – Vitamin B7.” The Nutrition Source, 7 Mar. 2023, www.hsph.harvard.edu/nutritionsource/biotin-vitamin-b7/.

Common name/scientific name: 

Milk thistle is a flowering herb known scientifically as Silybum marianum. It belongs to the Asteraceae family and is native to the Mediterranean, as well as parts of Africa and Russia.

What is it used for? 

Milk thistle is used for various medicinal purposes, with its primary applications being in support of liver health and to reduce fasting blood glucose in patients with diabetes mellitus. Regarding liver health, milk thistle is used to promote liver function and aid in the treatment of diseases such as cirrhosis, hepatitis, fatty liver disease and liver damage due to infection, alcoholism, and chemotherapy.

How does it work?

The key active ingredient in milk thistle is a flavonoid known as silymarin. Silymarin is believed to possess antioxidant and anti-inflammatory properties. The antioxidant action is essential for its hepatoprotective, glucose lowering, and, potentially, anticancer effects. Silymarin stabilizes cell membranes and acts as a free radical scavenger, preventing the entry of toxins into liver cells. Similarly, silymarin protects against DNA damage by hydrogen peroxides and inhibits mitogenic signaling pathways related to proliferation of androgen-dependent and -independent prostate cancer cells. Research suggests oxidative stress contributes to pancreatic beta-cell dysfunction, reduced insulin secretion, and insulin resistance; thus, silymarin exerts protective effects on the pancreas which likely contribute to fasting blood glucose reductions. Silymarin is believed to inhibit COX-II, regulate inflammatory mediators, and downregulate the synthesis of leukotrienes and prostaglandins. Milk thistle has also been shown to lower total cholesterol, triglycerides, and LDL cholesterol through inhibition of HMG-CoA reductase and VLDL synthesis.

What are some side effects?

Milk thistle is considered safe when used appropriately and for short durations in patients >1 year. Some individuals may experience mild side effects such as abdominal bloating, dyspepsia, nausea, diarrhea, and flatulence. If applied topically, the most common side effect is erythema. Allergic reactions, including anaphylaxis, are rare but may occur in individuals sensitive to the Asteraceae plant family (which includes ragweed, daisies, and chrysanthemums). Since milk thistle lowers blood glucose, using other medications with similar effects may increase the risk of hypoglycemia. Furthermore, milk thistle may mimic estrogen; avoid use in individuals with conditions that may be worsened by estrogen (breast, uterine, ovarian cancer).

Are there any trials that support its efficacy?

Efficacy evidence is inconsistent and existing studies vary in methodology, doses, and patient populations, making it challenging to draw firm conclusions. Additional high-quality trials are needed to establish a definitive conclusion on milk thistle’s benefit.

A meta-analysis revealed reductions of fasting blood glucose (~26 mg/dL) and A1c (~1%) in type 2 diabetes patients taking daily milk thistle for 6 months, with greater benefits shown in studies lasting < 3 months.

Studies in hepatitis B indicate some symptomatic improvement with milk thistle (such as reduced jaundice, dark urine, and scleral icterus), but evidence varies in terms of improving LFTs and liver histology. Patients with hepatitis C virus (HCV) showed improved liver function in some studies, whereas others reported no impact on LFTs or HCV RNA levels. Meta-analyses conclude the clinical effects of milk thistle in hepatitis are limited, lacking significant impacts on mortality, disease-related complications, or liver histology.

Nonalcoholic fatty liver disease (NAFLD) studies suggest milk thistle may slightly improve LFTs. Two met analyses showed reductions in AST (~7 IU/L) and ALT (~9-15 IU/L) levels; however, both suggested these reductions may not be clinically significant or reliably reflect liver histology. Other trials explore the combination of milk thistle with lifestyle modifications, with mixed results on BMI reductions and liver health markers in NAFLD patients.

Additional considerations (known drug interactions, special directions, etc.)

Drug interactions: Minor: decreased the effects of estrogens and statins.

Moderate: increased effects of raloxifene and tamoxifen, increased hypoglycemia risk with diabetes medications, increased anticoagulation with warfarin, and increased/decreased effects of morphine (milk thistle may bind mu-opioid receptors).

Pregnancy and lactation: there is insufficient, reliable data about safety in this population; avoid use.

Special directions: dosages and formulations can vary; follow recommended dosages on product labels or as directed by healthcare professionals to avoid increased risk of side effects.

References

Achufusi TGO, Patel RK. Milk thistle [updated 2022 Sep 12]. In: StatPearls [internet]. Treasure Island (FL): StatPearls Publishing. 2023 Jan. https://www.ncbi.nlm.nih.gov/books/NBK541075/

Fried MW, Navarro VJ, Afdhal N. Effect of silymarin (milk thistle) on liver disease in patients with chronic hepatitis c unsuccessfully treated with interferon therapy: a randomized controlled trial. JAMA. 2012 Jul;308(3):274-82. https://jamanetwork.com/journals/jama/fullarticle/1217238

Jacobs BP, Dennehy C, Ramirez G, et al. Milk thistle for the treatment of liver disease: a systematic review and meta-analysis. Am J Med. 2002 Oct;113(6):506-15. https://www-sciencedirect-com.jerome.stjohns.edu/science/article/pii/S0002934302012445

Milk thistle [updated 2023 Sep]. Natural Medicines. 2023. https://naturalmedicines-therapeuticresearch-com.jerome.stjohns.edu/databases/food,-herbs-supplements/professional.aspx?productid=138

Mirhashemi SH, Hakakzadeh A, Yeganeh FE, et al. Effect of 8 weeks milk thistle powder (silymarin extract) supplementation on fatty liver disease in patients candidates for bariatric surgery. Metabol Open. 2022 Jun;14:100190. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9149185/

Voroneanu L, Nistor I, Dumea R, et al. Silymarin in type 2 diabetes mellitus: a systemic review and meta-analysis of randomized controlled trials. J Diabetes Res. 2016 Jun;2016:5147468. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4908257/

Seaweed Supplements

Common Name/Scientific Name:

Seaweeds (Various species from Phaeophyceae, Rhodophyta, and Chlorophyta classes). Sold as seaweed supplements, sea moss, Irish sea moss, etc.

What is it used for?

Seaweeds serve as nutrient-rich food, containing minerals, vitamins (A, B1, B2, B9, B12, C, D, E, K), essential minerals (calcium, iron, iodine, magnesium, phosphorus, potassium, zinc, copper, manganese, selenium, fluoride), dietary fibers, proteins, essential amino acids, and polyphenols. They are consumed as whole food and utilized in various industries for bioactive compounds. Seaweed extracts are employed in agriculture, pharmaceuticals, biotechnology, and cosmetics.

How does it work?

Seaweeds offer health benefits through direct and indirect means. Directly, they can be consumed as whole food or as supplements, providing essential nutrients, antioxidants, and anti-inflammatory compounds. Indirectly, seaweeds are used in agriculture as biofertilizers, ensuring nutrient-rich soil and chemical-free crops, leading to positive health effects after consuming agricultural products. Bioactive compounds like fucoidans, carrageenans, and ulvan from different seaweed classes exhibit antibacterial, antiviral, anti-inflammatory, and anticoagulant properties.

Fucoidans from brown algae, like those found in Laminaria cichorioides and Fucus evanescens, have demonstrated anticoagulant activity comparable to heparin. Moreover, the antioxidant, anti-inflammatory, and anti-hyperglycemic activities of high-molecular-weight fucoidans extracted from Fucus vesiculosus suggest their potential as natural drugs.Agar extracted from red algae, such as Gracilaria edulis, serves as a suspension component in drug solutions and exhibits anticoagulant properties. Chlorophyta (green algae), rich in ulvan, a sulfate polysaccharide, finds applications in biomedicine, cosmetics, and pharmaceutical industries. Ulva rigida from Chlorophyta has demonstrated hypoglycemic effects in vivo.

Seaweeds also contribute to antiviral therapies. Polysaccharides extracted from Saccharina japonica show in vitro inhibition to SARS-CoV-2, suggesting their potential as natural antiviral agents. Compounds like griffithsin from red algae Griffithsia sp. exhibit antiviral activity against MERS-CoV and SARS-CoV glycoprotein.

What are some side effects?

While seaweeds are generally considered safe for consumption, it's crucial to be cautious about potential contamination by heavy metals and minerals, which can accumulate in seaweeds and may pose health risks if consumed excessively.

One must exercise caution regarding the iodine content in sea moss supplements, as excessive iodine intake can lead to adverse effects on thyroid function. The Jod-Basedow phenomenon, a rare cause of thyrotoxicosis due to excess iodine intake, may be triggered.

A case study reported a seemingly healthy individual who, unknowingly exacerbating underlying Grave's disease, experienced thyrotoxicosis due to prolonged intake of sea moss supplements. The patient's irregular consumption led to suppressing thyroid function and later caused accelerated hormone production, contributing to the Jod-Basedow phenomenon. Discontinuing sea moss resulted in clinical and biochemical improvement without requiring thionamide therapy.

It is important to note that Irish sea moss, a commonly available herbal supplement, contains variable amounts of iodine. While the recommended daily iodine intake is 150 mcg, sea moss may provide higher amounts. Patients with a history of hyperthyroidism or autoimmune thyroid disorders, such as Grave's disease, should be cautious about sea moss supplementation. Regular monitoring of thyroid function and consultation with healthcare professionals are crucial to prevent potential complications.

Are there any trials that support its use/non-use (efficacy)?

Numerous trials support the efficacy of seaweed bioactive compounds and are included in the references section. Just to list a few interesting ones: Fucoidans from Laminaria cichorioides and Fucus evanescens exhibit anticoagulant activity similar to heparin. Sargassum fulvellum extracts demonstrate pharmacological effects such as antioxidant, anticancer, anti-inflammatory, antibacterial, and anticoagulant activities. Polysaccharides from Saccharina japonica show in vitro inhibition to SARS-CoV-2, indicating potential antiviral properties. Studies also highlight the role of seaweed-derived compounds in cardiovascular health, metabolic syndrome, weight management, and as a sustainable source of omega-3 polyunsaturated fatty acids.

Additional Considerations:

It's essential to monitor and research potential harmful compounds in seaweeds, such as heavy metals and minerals. The use of seaweed bioactive compounds in biotechnological and industrial applications promotes a healthier lifestyle in a sustainable way. Ongoing research is needed to identify and neutralize potentially harmful compounds while increasing the application of seaweed compounds in various industries.

References:

Berteau O Mulloy B . Sulfated fucans, fresh perspectives: structures, functions, and biological properties of sulfated fucans and an overview of enzymes active toward this class of polysaccharide. Glycobiology. 2003;13:29R–40R.

Emma M Brown, Philip J Allsopp, Pamela J Magee, Chris IR Gill, Sonja Nitecki, Conall R Strain, Emeir M McSorley, Seaweed and human health, Nutrition Reviews, Volume 72, Issue 3, 1 March 2014, Pages 205–216

Khalifa M, Aftab HB, Kantorovich V. “Fueling the Fire” - Irish Sea-Moss Resulting in Jod-Basedow Phenomenon in a Patient With Grave’s Disease. J Endocr Soc. 2021 May 3;5(Suppl 1):A906.

Kwon P.S., Oh H., Kwon S.-J., Jin W., Zhang F., Fraser K., Hong J.J., Linhardt R.J., Dordick J.S. Sulfated polysaccharides effectively inhibit SARS-CoV-2 in vitro. Cell Discov. 2020;6:50.

Lomartire S, Marques JC, Gonçalves AMM. An Overview to the Health Benefits of Seaweeds Consumption. Mar Drugs. 2021 Jun 15;19(6):341

Millet J.K., Séron K., Labitt R.N., Danneels A., Palmer K.E., Whittaker G.R., Dubuisson J., Belouzard S. Middle East respiratory syndrome coronavirus infection is inhibited by griffithsin. Antiviral Res. 2016;133:1–8

Paradis ME Couture P Lamarche B . A randomised crossover placebo-controlled trial investigating the effect of brown seaweed (Ascophyllum nodosum and Fucus vesiculosus) on postchallenge plasma glucose and insulin levels in men and women. Appl Physiol Nutr Metab. 2011;36:913–919.

Yoon S.J., Pyun Y.R., Hwang J.K., Mourão P.A.S. A sulfated fucan from the brown alga Laminaria cichorioides has mainly heparin cofactor II-dependent anticoagulant activity. Carbohydr. Res. 2007;342:2326–2330.

Zumla A., Chan J.F.W., Azhar E.I., Hui D.S.C., Yuen K.Y. Coronaviruses-drug discovery and therapeutic options. Nat. Rev. Drug Discov. 2016;15:327–347

GINGER

Common Name/Scientific Name:

Names include Ginger, Zingiber officinale, Zingiberaceae, Amomum Zingiber, Ardraka, Gan Jiang, Gingembre

What is it used for?

Ginger can be used in any form; fresh, dry, preserved, powdered, and even crystallized. It can be taken by mouth, as a supplement or tea, used topically, or even eaten raw. Ginger has anti-fungal, antibacterial, and antioxidant properties It has shown evidence of protecting against ethanol-induced hepatotoxicity. Ginger can also be used in the treatment of pain and swelling in patients with rheumatoid arthritis, osteoarthritis, or muscle cramps/pain.  Other treatments of ginger include sore throats, cramps, asthma, and stroke. Ginger has shown effects on lowering blood sugar, so when used correctly, can help patients with pre-diabetes or diabetes mellitus. Ginger has also been shown to decrease blood pressure, treating hypertension. Ginger has also been used to treat nausea and vomiting, which may have been caused by pregnancy and chemotherapy, due to its gastroprotective properties.

How does it work?

Ginger works in similar ways as NSAIDS, like ibuprofen and naproxen. It inhibits COX1 and COX2 function which then suppresses the synthesis of prostaglandin. Unlike NSAIDS, Ginger also inhibits 5-lipoxygenase, therefore, inhibiting leukotriene synthesis. Both leukotriene and prostaglandins cause inflammation. By inhibiting them, ginger provides anti-inflammatory effects. Ginger has antioxidant properties and inhibits lipid peroxidase. This allows ginger to be used as a gastro-protective agent. Its gastroprotective properties are also contributed by ginger's stimulation of muscarinic receptors and inhibition of 5-HT receptors. By increasing muscaranic receptors, gastric motility increases.

What are some side effects?

There has been increased bleeding in patients taking ginger, therefore it’s recommended to avoid taking ginger supplements if patients have high bleeding risk. Other mild adverse effects include headache, stomach upset, and allergic reactions (hives, itching, burning of the skin). Ginger also has shown effects of heartburn, diarrhea, mouth irritation, and stomach upset.

Are there any trials that support its use/non-use (efficacy)? Provide details.

A study was done on rats with ethanol toxicity to evaluate the effects of ginger on oxidative stress. The rats were held in cages with a rat pellet diet and water. They were each given 1% body weight of ginger. According to the results, this 1% ginger intake was able to reverse the oxidative stress ethanol placed on the rats in 4 weeks.

In another preclinical study, ginger was shown to inhibit Helicobacter pylori infection. The ginger was proved effective in inhibiting the growth of H. pylori, even against the CagA+ strains, showing effects better than lansoprazole. The study showed pretreating with standard ginger dosing (100mg/kg) reduced the load of H. pylori and its side effects on mice. These side effects included mucosal and submucosal inflammation, cryptitis, and cell degeneration.

Additional Considerations

- Caution when taken with anticoagulants, such as warfarin and heparin, and anti platelet drugs, such as aspirin and clopidogrel.

- Due to its effects on the blood, avoid taking ginger for a few weeks before scheduled surgery and before the due date if pregnant.

- Caution in patients with diabetes due to its effects on blood sugar.

- Caution in patients taking hypertension medication, due to ginger's effects on blood pressure

- The common dose of ginger is 0.5-3 grams (no more than 4g) by mouth daily for up to 12 weeks

Grzanna, Reinhard et al. “Ginger--an herbal medicinal product with broad anti-inflammatory actions.” Journal of medicinal food vol. 8,2 (2005): 125-32. doi:10.1089/jmf.2005.8.125

Haniadka, Raghavendra et al. “A review of the gastroprotective effects of ginger (Zingiber officinale Roscoe).” Food & function vol. 4,6 (2013): 845-55. doi:10.1039/c3fo30337c

Food, Herbs, & Supplements (Chromium)

Common Name/Scientific Name: 

Common Name: Chromium

Scientific Name: Chromium picolinate

What is Chromium used for?

Chromium is a mineral that is commonly used as a dietary supplement. It is primarily taken to improve blood sugar control in people with type 2 diabetes and to support weight loss efforts. It helps keep blood glucose levels by improving the ways the body uses insulin. Some individuals also take chromium supplements to enhance muscle mass and improve athletic performance. 

How does Chromium work?

Chromium is an essential trace mineral that plays a role in insulin signaling and glucose metabolism. It enhances the action of insulin, a hormone responsible for regulating blood sugar levels. By improving insulin sensitivity, chromium helps cells take up glucose more effectively, thereby reducing blood sugar levels. This mechanism is particularly beneficial for individuals with insulin resistance, a common characteristic of type 2 diabetes.

What are some side effects?

Chromium supplements are generally considered safe when taken within the recommended doses. However, some individuals may experience mild side effects, such as headaches, dizziness, nausea, and digestive discomfort. In rare cases, high doses of chromium have been linked to more severe side effects, including kidney damage and liver toxicity. It is crucial to follow the recommended dosage guidelines and consult a healthcare professional before starting chromium supplementation.

Are there any trials that support its use/non-use (efficacy)? Provide details.

Research on the efficacy of chromium supplementation for blood sugar control and weight loss has yielded mixed results. Some studies have shown modest improvements in blood sugar levels and insulin sensitivity in people with type 2 diabetes, while others have not found significant benefits. Similarly, regarding weight loss, some studies suggest a small reduction in body weight and fat mass, while others report no significant effects.

The American Diabetes Association and other health organizations have stated that there is not enough evidence to recommend chromium supplementation as a standard treatment for diabetes. However, some healthcare providers may consider it as an adjunct therapy for select patients. The effectiveness of chromium for weight loss remains uncertain, and its use should not be solely relied upon as a primary strategy for managing obesity.

Additional Considerations

Drug Interactions: Chromium supplements may interact with certain medications, including antacids, corticosteroids, beta-blockers, and nonsteroidal anti-inflammatory drugs (NSAIDs). More specifically, it can cause an increase in insulin sensitivity causing possibly hypoglycemia when taken concomitantly with insulin. It also has a blood glucose-lowering effect so taking it with other diabetic medications like metformin can increase the risk of hypoglycemia. Also, a small study found it can cause lowering absorption of levothyroxine. 

Special Directions: Always follow the recommended dosage provided on the supplement label or as prescribed by a healthcare professional. Taking excessive amounts of chromium can be harmful and may increase the risk of adverse effects. Pregnant or breastfeeding women, as well as individuals with kidney or liver conditions, should exercise caution and seek medical advice before using chromium supplements.

1. Office of Dietary Supplements - Chromium. (2023). Retrieved 19 July 2023, from https://ods.od.nih.gov/factsheets/Chromium-HealthProfessional/ 

2. Jenny E. Gunton, N. Wah Cheung, Rosemary Hitchman, Graham Hams, Christine O’Sullivan, Kaye Foster-Powell, Aidan McElduff; Chromium Supplementation Does Not Improve Glucose Tolerance, Insulin Sensitivity, or Lipid Profile: A randomized, placebo-controlled, double-blind trial of supplementation in subjects with impaired glucose tolerance. Diabetes Care 1 March 2005; 28 (3): 712–713. https://doi.org/10.2337/diacare.28.3.712 

Ginkgo Biloba

Common Names: Ginkgo, ginkgo biloba, fossil tree, maidenhair tree, Japanese silver apricot, baiguo, yinhsing

Scientific Name: Gingko biloba L. maidenhair tree (Ginkgoaceae)

What is it used for?

Gingko biloba is one of the most commonly used herbal supplements in the world. There is no FDA approved indication and insufficient evidence to support non-FDA approved use of Gingko. The extract from ginkgo leaves is promoted as a dietary supplement for many conditions, including dementia, Alzheimer’s disease, and other conditions associated with cerebral vascular insufficiency, including memory loss, headache, tinnitus, vertigo, difficulty concentrating, mood disturbances, and hearing disorders. It can also be used as an anti-hypertensive, in diabetic retinopathy and macular degeneration, and retinal damage with poor color vision. Despite the wide use of Ginkgo, its efficacy in the prevention and treatment of dementia remains controversial.

How does it work?

Ginkgo has two primary active ingredients: terpene lactones and ginkgo flavone glycosides. The extract has been shown to affect several neurotransmitter pathways and brain structures. It appears to have reversible inhibitory effects on reuptake of serotonin and dopamine and increased cholinergic transmission in the brain. It acts as a free radical scavenger and protects neurons from oxidative damage and apoptosis, which have been prominently observed in Alzheimer disease. Gingko also acts as a peripheral vasodilator by increasing nitric oxide thus improving blood flow through the small vessels. It also acts as an anti-platelet which is why it is advised to be used with caution in patients with increased bleeding risk.

What are some side effects?

The maximum recommended dose for gingko extract is 240 mg/day. Side effects of ginkgo may include headache, stomach upset, dizziness, palpitations, constipation, and allergic skin reactions.

Are there any trials that support its use/non-use (efficacy)? Provide details.

The use of Ginkgo biloba extract in the treatment for existing dementia has been contradictory. In a 52-week randomized double blind, placebo-controlled, parallel-group, multicenter study of 309 patients. The study concluded that Ginkgo extract was safe and though modestly, it appeared to stabilize and improve cognitive performance as well as social functioning of dementia in patients for six months to one year. In another 24-week randomized controlled trial of 410 patients it also found that 240mg once daily was safe and statistically significant improvement in cognition was seen. However, in a randomized controlled trial of 513 outpatients with mild to moderate dementia that found that ginkgo extract was not effective. A systematic review of 36 trials though demonstrating the safety of this supplement did not support any clinical benefit for patients with cognitive impairment of dementia. Various studies continue to outline contradicting findings to support either the use or non-use of this supplement.

Additional Considerations (drug interactions, special directions, etc.)

Ginkgo biloba is known to increase bleeding risk by decreasing the blood clotting capabilities and is therefore advised against in patients with bleeding disorders or those taking NSAIDs. Ginkgo also has properties as a monoamine oxidase inhibitor that can precipitate serotonin syndrome in patients on other antidepressant medications. It also has several interactions with other dietary supplements. If taken during pregnancy, it is considered unsafe and may cause early labor or extra bleeding during delivery. Raw gingko can contain dangerous amounts of a toxin called ginkgo-toxin which may cause seizures and alkylphenol ginkgolic acid which is a carcinogen and allergen.

References

Tan, M. S., Yu, J. T., Tan, C. C., Wang, H. F., Meng, X. F., Wang, C., Jiang, T., Zhu, X. C., & Tan, L. (2015). Efficacy and adverse effects of ginkgo biloba for cognitive impairment and dementia: a systematic review and meta-analysis. Journal of Alzheimer's disease : JAD, 43(2), 589–603. https://doi.org/10.3233/JAD-140837

Nguyen T, Alzahrani T. Ginkgo Biloba. [Updated 2022 Jul 4]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK541024/

Ginkgo. (n.d.). NCCIH. https://www.nccih.nih.gov/health/ginkgo

Singh, S. K., Srivastav, S., Castellani, R. J., Plascencia-Villa, G., & Perry, G. (2019). Neuroprotective and Antioxidant Effect of Ginkgo biloba Extract Against AD and Other Neurological Disorders. Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 16(3), 666–674. https://doi.org/10.1007/s13311-019-00767-8

Food, Herbs, and Supplements: St. John’s Wort

Common Name/Scientific Name:

Common Name: St. John’s Wort

Scientific Name: Hypericum perforatum

Use

St. John’s Wort is an invasive, flowering plant native to Europe and Asia and belongs to the Hypericaceae family and the species of the genus Hypericum. The name St. John’s wort refers to the priest, John the Baptist, since the plant blooms in late June, the time of the feast of St. John the Baptist. The plant’s flowers have a distinctive yellow color and are short-lived perennial shrubs that grow up to 1-2 feet. Its medicinal properties are derived from its stem, petals, and flowers. St John’s wort has been used for its antibacterial, antiviral, antidepressive, anti-inflammatory, and antioxidant properties dating back to ancient Greece, now available over the counter topically or as an oral herbal dietary supplement and is not FDA approved. It is indicated for those with mild to moderate depression, menopausal symptoms, ADHD, somatic symptom disorder, and obsessive-compulsive disorder. It can be used for nerve pain, anxiety, insomnia, and pain from sciatica, rheumatoid arthritis, and menstruation. Topically, it aids in wound healing from mild burns and sunburns, bruising, varicose veins, and muscle pain. It may take 4 to 6 weeks to see efficacy and is typically orally administered 300 to 400 mg three times a day with meals for the treatment of mild depression and mood disorders. Tinctures, teas, or liquid extracts are also available.

Mechanism of Action

St. John’s Worts therapeutic actions stem from its bioactive chemical makeup of flavonol derivatives, biflavones, proanthocyanidins, xanthones, phloroglucinols and naphthodianthrones. One of the principal mechanisms of action of this plant is that it acts as a serotonin reuptake inhibitor, which reduces the uptake of serotonin at neuronal synapses, thereby increasing levels of serotonin in the body. It also prevents the reuptake of dopamine and norepinephrine. Those suffering from depression may have a chemical imbalance of serotonin, hence, increasing serotonin through reuptake inhibition is used to treat this condition. Moreover, this supplement activates pregnane-X-receptor (PXR) cytochromes, thereby inducing the cytochrome P450 system, CYP3A4 enzyme and P-glycoprotein. P450s or monooxygenase enzymes metabolize the compound through hydroxylation, making it more polar, which increases its reactivity for conjugation into various polar groups. St John’s wort also inhibits monoamine oxidase A and B, which are enzymes responsible for the degradation of dopamine, serotonin, and norepinephrine. Through its monoamine oxidase inhibition, taking this supplement will increase norepinephrine levels. The bioactive constituent responsible for St. John’s wort’s antidepressant and anxiolytic effects is the phytochemical compound, hyperforin. Hyperforin acts as a serotonin and monoamine reuptake inhibitor, as well as GABA and glutamate, and activates the transient receptor potential ion channel, TRPC6. TRPC6 activation allows for the entry of sodium and calcium into the cell, which causes monoamine reuptake inhibition. Likewise, hyperforin induces CYP3A4 and CYP2C9 enzymes through binding and activation of pregnane X receptor (PXR).

Antidepressant activity is also seen due to the supplement’s activation of GABA receptors. Malfunctioning of GABA receptors can cause depression and anxiety; therefore, activating these receptors can help with mood regulation. St. John’s wort also plays in the downregulation (decrease the number of) of beta-adrenergic receptors and upregulation (increase the number of) of serotonin receptors. Beta-adrenergic receptors are activated upon the binding of epinephrine, which leads to increased heart rate and blood pressure. Due to downregulation, there is less opportunity for epinephrine to stimulate the beta-adrenergic receptors, which provide a calming effect. On the other hand, upregulation of serotonin receptors increases the chance for serotonin stimulation, thereby decreasing depressive and anxiolytic symptoms.

Side Effects, Drug Interactions, and Additional Considerations

Side effects of St. John’s Wort include insomnia, anxiety, dry mouth, dizziness, gastrointestinal symptoms, fatigue, headache, or sexual dysfunction.

There are numerous drug interactions in those taking St. John’s wort with other medications due to its induction of CYP3A4 and P-glycoprotein drug efflux transporter.

These include the following:

Decreased therapeutic efficacy of:

-Antidepressants -HIV protease inhibitors

-Birth control pills -Cancer medications, irinotecan and imatinib

-Cyclosporine -Warfarin

-Digoxin and Ivabradine -Statins

Given St. John’s wort’s mechanism of action, concomitant administration of this supplement with SSRIs may put the individual at risk for serotonin syndrome (mental confusion, agitation, sweating, tachycardia). There is an associated risk of those with bipolar depression taking St. John’s wort since it may induce manic episodes. It is advised to avoid St. John’s wort in these patients.

Additionally, St. John’s Wort may cause increased sensitivity to sunlight when taken in large doses. In regards to side effects of its topical form, it may cause severe skin reactions upon sun exposure. Therefore, it is advised in patients taking this supplement to wear sunscreen regularly and avoid sun exposure.

There is little evidence in regards to the supplement’s safety in a pregnant patient. In vitro animal studies do not show that it affects brain development or behavioral defects; however, low birth weight may occur. Further there is little evidence that the herb does not cross through breast milk or does not affect breast milk production. Additional studies need to be conducted to determine its safety in pregnant populations, and it must be used with caution.

Supporting Trials

A meta-analysis of 27 studies (total of 3,126 depressed patients) comparing efficacy and safety of St. John’s wort with SSRIs for the treatment of depression in adults from 1966 to April 2015 showed no difference in regards to clinical response, remission, and mean reduction in the Hamilton Rating Scale for Depression (HAMD) score. The primary outcome measure for treatment efficacy and safety was a change in total HAMD score between baseline and endpoint. The outcome of interest include: responder rate (reduction in HAMD score by 50%) remission rate (reduction in HAMD score by 75%), mean reduction in HAMD score, incidence of adverse events, total withdrawal rate, and withdrawals due to adverse events. St. John’s wort extract had a lower rate of adverse events compared to SSRIs evidenced by a summary relative risk: 0.77; 95% confidence interval: 0.70, 0.84, P=0.00. The safety profile of this supplement compared to SSRIs is superior. The findings of this meta analysis revealed that St. John’s Wort is comparable to SSRIs in efficacy but superior in safety evidenced by lower rates of adverse events and withdrawal due to adverse events.

References

Cui, Yong-Hua, and Yi Zheng. “A Meta-Analysis on the Efficacy and Safety of St John’s Wort Extract in Depression Therapy in Comparison with Selective Serotonin Reuptake Inhibitors in Adults.” Neuropsychiatric Disease and Treatment, 11 July 2016, www.ncbi.nlm.nih.gov/pmc/articles/PMC4946846/.

G;, Dugoua JJ;Mills E;Perri D;Koren. “Safety and Efficacy of St. John’s Wort (Hypericum) during Pregnancy and Lactation.” The Canadian Journal of Clinical Pharmacology = Journal Canadien de Pharmacologie Clinique, 3 Nov. 2006, pubmed.ncbi.nlm.nih.gov/17085775/#:~:text=Conclusions%3A%20Caution%20is%20warranted%20with,but%20may%20cause%20side%20effects.

“Hyperforin.” Uses, Interactions, Mechanism of Action | DrugBank Online, go.drugbank.com/drugs/DB01892. Accessed 18 May 2023.

Peterson, Bahtya, and Hoang Nguyen. “National Center for Biotechnology Information.” St. John’s Wort, 19 May 2022, www.ncbi.nlm.nih.gov/books/NBK557465/.

Schwartz, Allan, and Mark Dombeck. “Major Depression and St. John’s Wort.” MentalHelp.Net, 26 Mar. 2019, www.mentalhelp.net/depression/st-john-s-wort/.

“St. John’s Wort.” National Center for Complementary and Integrative Health, Oct. 2020, www.nccih.nih.gov/health/st-johns-wort.

V;, Butterweck. “Mechanism of Action of St John’s Wort in Depression : What Is Known?” CNS Drugs, pubmed.ncbi.nlm.nih.gov/12775192/. Accessed 18 May 2023.

Nicotinamide for Non-Melanoma Skin Cancer Prevention

Nicotinamide (NAM) is an amide form of vitamin B3 which is a semi-essential vitamin. According to the FDA, the recommended daily intake of vitamin B3 for adults and children >4 years old is 16 mg. Certain foods like meat, fish, legumes, mushrooms, nuts, and grains contain NAM but if we do not consume enough in our diet, supplementation may be warranted. Those at the highest risk for deficiency would be those with conditions which impair absorption or limit consumption such as people with anorexia nervosa, malnutrition, alcohol use disorder, inflammatory bowel disease, and AIDS. Deficiency in NAM affects tissues that need high cellular energy such as the brain, gut, and skin. Supplementation with NAM is specifically recommended for patients with pellagra which is vitamin B3 deficiency presenting as dermatitis, diarrhea, and dementia.

Once ingested, NAM is converted into nicotinamide adenine dinucleotide, or NAD+. NAD+ is a necessary part of many different enzyme reactions in the body. It is especially an essential co-enzyme of redox reactions for adenosine triphosphate (ATP) production and lipid metabolism. Niacin which is converted to nicotinamide in the body is indicated for treatment of dyslipidemias due to its ability to reduce total cholesterol, apolipoprotein B, triglycerides, LDL, and VDL as well as increase HDL. In addition to supplementation with NAM for prevention of pellagra it has also been studied for the prevention of non-melanoma skin cancers in high risk patients.

Non-melanoma skin cancers are caused primarily by exposure to UV radiation. UV radiation increases the risk of skin cancer by damaging DNA, suppressing cutaneous antitumor immunity and inhibiting DNA repair by depleting cellular ATP. Since NAD+ is an essential cofactor for ATP production, it has been investigated for prevention of these cancers. It can prevent the ATP depletion and glycolic blockade induced by UV radiation which increases cellular energy and enhances DNA repair.

In a phase 3, double-blind, randomized, controlled trial the efficacy of oral nicotinamide for the chemoprevention of non-melanoma skin cancer in a high-risk population was studied. The 386 participants who had at least two non-melanoma skin cancers in the past 5 years were randomized to receive 500 mg of nicotinamide twice daily or placebo for 12 months. The primary endpoint was number of new non-melanoma skin cancer during the 12 months. At 12 months the rate of new non-melanoma skin cancer was lower by 23% in the nicotinamide group than in the placebo group (P = 0.02). Safety results showed no significant difference between the nicotinamide group and placebo group with limited side effects. These favorable results along with the low cost of oral nicotinamide supplements suggests that it may be a feasible option for the prevention of non-melanoma skin cancer along with other recognized prevention strategies such as limiting sun exposure and covering skin when exposure is unavoidable.

Resources:

Chen AC, Martin AJ, Choy B, et al. A phase 3 randomized trial of nicotinamide for skin-cancer chemoprevention. New England Journal of Medicine. 2015;373(17):1618-1626. doi:10.1056/nejmoa1506197

Fania L, Mazzanti C, Campione E, Candi E, Abeni D, Dellambra E. Role of Nicotinamide in Genomic Stability and Skin Cancer Chemoprevention. Int J Mol Sci. 2019;20(23):5946. Published 2019 Nov 26. doi:10.3390/ijms20235946

Green Tea

Common Name: green tea

Scientific Name: Camellia sinensis

What is it used for?

Tea has been used for medicinal purposes for thousands of years in China, Japan and India. Now, tea is the second most widely consumed beverage in the world. In traditional medicine, green tea is used as a stimulant, diuretic- to help rid excess fluids, and astringent- to control bleeding and help heal wounds. It is also used to treat gas, and regulate body temperature and blood sugar. Green tea improves mental alertness, relieves digestive symptoms and headaches, and promotes weight loss. It may also have protective effects against heart disease and cancer. There are studies indicating that the antioxidant properties of green tea may prevent atherosclerosis, particulary coronary artery disease. It may also lower total cholesterol and raise HDL (good cholesterol). Green tea may also help with inflammatory bowel disease by reduce inflammation in Crohn disease and ulcerative colitis. There is also a FDA approved topical ointment named Veregen, which contains sinecatechins or extracted components of green tea leaves, and is used for the treatment of genital warts.

How does it work?

The health benefits of green tea is thought to be due to polyphenols, which are chemicals with potent antioxidant potential. These antioxidants have antimutagenic, antidiabetic, antibacterial, antiinflammatory, and hypocholesterolemic properties. These polyphenols are classified as catechins- catechin, gallaogatechin, epicatechin, epigallocatechin, epicatechin gallate, and apigallocatechin gallate (also known as EGCG). EGCG is the most studied polyphenol component in green tea and the most active. Green tea also contains alkaloids- caffeine, theobromine and theophylline, which provides the stimulant effects. Lastly, it also contains L-theanine, which proves the calming effects.

What are some side effects?

Green tea is generally safe up to 8 cups per day. However, during pregnancy and breastfeeding, consuming green tea is safe up to 6 cups per day or no more than 300 mg of caffeine. Those who drink a large amount of caffeine may experience irritability, insomnia, heart palpitations and dizziness. Overdose of caffeine can cause nausea, vomiting, diarrhea, headaches and loss of appetite. Caffeine poisoning is when you start to vomit or have abdominal spasms after drinking a lot of tea.

With green tea extracts in pill form, there has been reports of liver problems such as abdominal pain, dark urine or jaundice. Therefore, people with liver disease should consult a health care provider before taking these products.

Are there any trials that support its use/non-use (efficacy)? Provide details.

· A 2006 meta-analysis of epidemiologic studies found that high intake of green tea was associated with a 20 percent reduction in the risk of breast cancer.

· A second meta-analysis found that high consumption of green tea was associated with an 18 percent reduction in the risk of colorectal cancer.

· 18,000 men were studied, and it was found that those who drank green tea were about one half as likely to develop stomach or esophageal cancer as men who drank little tea.

· 240 obese adults were studied for 12 weeks with a green tea extract beverage high in catechins and a lower catechin placebo; The results showed that the active treatment group had greater reductions in body weight, body mass index, body fat ratio, body fat mass, and waist and hip circumference.

· 40,000 Japanese adults were studied and it was found that green tea consumption was inversely associated with cardiovascular disease mortality.

· 1,000 Japanese adults in their 40s were studied and found no association between green tea intake and total cholesterol level.

· 240 Chinese adults with mild to moderate hypercholesterolemia who received a once-daily theaflavin-enriched green tea extract reduced their LDL by 16.4 percent ± 1.1 percent (P < .01) and their total cholesterol by 11.3 percent ± 0.9 percent compared with placebo.

Additional Considerations (Can include known drug interactions, special directions, etc.)

· Green, black and oolong tea comes from the leaves of the Camellia sinensis plant.

· To make green tea, the unfermented leaves from the plant are steamed, pan fried and dried.

· Among the teas, green tea contains the highest concentration of powerful antioxidants, polyphenols.

· The main component of green tea, EGCG, does not improve mental capabilities. It is the caffeine in the tea that prevents a decline in alertness.

· Amount of caffeine on green tea products indicates only the amount of added caffeine. It does not include the caffeine that are naturally in green tea.

· Green tea dietary supplements are capsules with dried leaf tea or liquid extracts made from the leaves and leaf buds.

· Average cup of green tea has 50 -150 mg of polyphenols. Decaffeinated green tea products contains concentrated polyphenols.

· 2 to 3 cups of green tea or 100 to 750 mg of standardized green tea extract per day is recommended

· Some drug interactions include adenosine, beta-lactam, benzodiazepines, beta blockers, blood thinning medications, clozapine, ephedrine, lithium, MAOIs, birth control pills, phenylpropanolamine, quinolone antibiotics, and others.

References

1. “Green Tea.” Mount Sinai Health System, https://www.mountsinai.org/health-library/herb/green-tea.

2. “Green Tea.” National Center for Complementary and Integrative Health, U.S. Department of Health and Human Services, https://www.nccih.nih.gov/health/green-tea.

3. Schneider C, Segre T. Green tea: potential health benefits. Am Fam Physician. 2009;79(7):591-594.

Asian Ginseng

Common Name: Chinese ginseng, Korean ginseng

Scientific Name: Panax ginseng

What is it used for?

It is an herb used in Chinese medicine for thousands of years, primarily to treat weakness and fatigue. Ginseng products are referred to as tonics or adaptogens, which means an agent that increases resistance to physical, chemical and biological stress and builds up general vitality. Asian ginseng is used to increase resistance to environmental stress and to improve well-being. It is also used as a dietary supplement to improve physical stamina, concentration, and memory; stimulate immune function; reduce the risk of certain cancers; slow the aging process and relieve various health problems such as respiratory and cardiovascular disorders, diabetes, depression, anxiety, menopausal hot flashes and erectile dysfunction.

How does it work?

It contains substances called ginsenosides or panaxosides, which are thought to be the active ingredient. It affects the hypothalamus-pituitary adrenal axis and the immune system. It also enhances phagocytosis, natural killer cell activity, and the production of interferon; causes vasodilation; increases resistance to exogenous stress factors and affects hypoglycemic activity.

What are some side effects?

Ginseng appears to be well-tolerated, but there are still side effects. If taken at high doses or with caffeine, it may cause nervousness or sleepiness. Some common side effects are insomnia, menstrual problems, breast pain, increased heart rate, high or low blood pressure, headache, loss of appetite and digestive problems. Some rare side effects are restlessness, anxiety, euphoria and nose bleed.

Are there any trials that support its use/non-use (efficacy)? Provide details.

· 227 healthy volunteers demonstrated that daily administration of 100 mg of ginseng for 12 weeks enhanced the efficacy of polyvalent influenza vaccine. Those who took ginseng had a lower incidence of influenza and colds, higher antibody titers and higher natural killer cell activity levels.

· 323 healthy volunteers were given 400mg of ginseng or placebo daily for 4 months. Those who had ginseng had fewer colds that were less severe and shorter than the colds of those who had placebo.

· 36 newly diagnosed non-insulin dependent diabetic patients were given 100 or 200mg per day for 8 weeks. The study showed improved fasting blood glucose levels, elevated mood, and improved psychophysical performance. Patients that took the 200mg dose also had improved hemoglobin A1C values.

Additional Considerations (Can include known drug interactions, special directions, etc.)

· Asian ginseng is a gnarled root with stringy shoots resembling a human body with 2 arms and 2 legs. The wrinkles around the neck of the root correspond to the age of the plant. Ginseng is not used as medicine until it has grown for about 6 years.

· There are white ginseng and red ginseng. White ginseng is dried and peeled, whereas red ginseng is unpeeled and steamed before drying.

· Asian ginseng supplements are made from the root and root hairs. They are available in water, water and alcohol, or alcohol liquid extracts, and in powders or capsules. They are also available as a decoction if the Asian ginseng root is boiled in water.

· The common daily dose of 200 mg of Asian ginseng extract or 0.5 to 2 g of dry ginseng root. Products with 4% ginsenoside content are standard.

· Asian ginseng should not be taken continuously, instead taken in cycles. For example, taking it every day for 3 weeks, then stopping for 3 weeks, and then restarting. It is a time-honored approach to strengthen the body and to treat the disease.

· Asian ginseng interacts with many medications such as ACE inhibitors, calcium channel blockers, anticoagulants and antiplatelets, caffeine, diabetes medications, including insulin, drugs that suppress the immune system, stimulants, MAOIs, morphine, furosemide, and others.

· Asian ginseng may also be unsafe to take during pregnancy.

· Asian ginseng should also not be given to infants and children.

· Check with a healthcare provider before taking Asian ginseng.

References

1. “Asian Ginseng.” Mount Sinai Health System, https://www.mountsinai.org/health-library/herb/asian-ginseng.

2. “Asian Ginseng.” National Center for Complementary and Integrative Health, U.S. Department of Health and Human Services, https://www.nccih.nih.gov/health/asian-ginseng.

3. Kiefer D, Pantuso T. Panax ginseng. Am Fam Physician. 2003;68(8):1539-1542.

Vitamin D Supplements

Common Name/Scientific Name:

Vitamin D3 / Cholecalciferol

What is it used for?

This supplement is given to adults who a vitamin D deficient, which can result in loss of bone mineral content, bone pain, and muscle weakness and soft bones.

How does it work?

Majority of the population receive less than optimal levels of vitamin D. The body naturally produces vitamin D through exposure to the sun. However, the sun is often not strong enough to meet the body’s needs. There are many reasons why the body isn’t able to produce the amount of vitamin D it needs. Some of these reasons are limited sun exposure during the winter months, older age, darker skin pigmentation, and use of sunscreen or clothes that shade the skin from the sun. Vitamin D is necessary for maintaining proper bone integrity, proper neuromuscular function, normal inflammatory response, muscle strength, proper calcium absorption, healthy immune response, and normal blood pressure. Having adequate vitamin D levels is also linked to decreased stress fractures, decreased injuries in athletes, and decreased rated of upper respiratory tract infections. Obtaining normal vitamin D levels can be through certain foods or supplements. Vitamin D supplements are fat soluble vitamins that can be taken orally and help the body absorb calcium and phosphorus. The absorption of calcium helps with building and keeping strong bones.

What are some side effects?

Vitamin D supplements are considered to be very safe and toxicity is very uncommon. The reason for this is because for vitamin d toxicity to occur, a healthy person would have to extremely large doses of vitamin D over a long period of time in order to reach dangerous or toxic levels of it. Some of the symptoms of vitamin D toxicity are chest pain, shortness of breath, growth problems for children taking cholecalciferol, weakness, metallic taste in the mouth, weight loss, muscle or bone pain, constipation, nausea, and vomiting. Although these side effects are uncommon, they can still occur if an individual were to overdose on vitamin D. However, vitamin D toxicity is more common in people with certain medical conditions. These conditions include granulomatous disorders, congenital disorders, some lymphomas, and dysregulated vitamin D metabolism.

Are there any trials that support its use/non-use (efficacy)? Provide details.

There have been many trials that have been conducted to evaluate the benefits of vitamin D supplements. I found a review article discussing the results of three different trials, VITAL, ViDA and D2d. These were all randomized trials and the combined number of participants of all three are over 30,000. One of the key takeaways from these trials are that Vitamin D and calcium supplementation can modestly decrease risk of major fractures in older adults. Also, there has been delays in age related bone loss and progression to type 2 diabetes and improved lung function. Another benefit is that they found vitamin d supplementation resulted in a modest decrease in cancer mortality, but has not affect on cancer risk. There hasn’t been any drastic or obvious benefits, with using vitamin d supplements, but correcting vitamin d deficiency remains essential.

References:

1. Bouillon, R., Manousaki, D., Rosen, C. et al. The health effects of vitamin D supplementation: evidence from human studies. Nat Rev Endocrinol 18, 96–110 (2022). https://doi.org/10.1038/s41574-021-00593-z

2. Spritzler, Franziska. “6 Side Effects of Too Much Vitamin D.” Healthline, Healthline Media, 15 Dec. 2021, https://www.healthline.com/nutrition/vitamin-d-side-effects#1.-Elevated-blood-levels.

Gastric Bypass and Nutritional Deficiencies

Gastric bypass is a type of bariatric surgery that is highly effective in treating obesity. It is a surgical procedure in which a portion of the stomach becomes bypassed, creating a smaller pouch, and connecting that smaller pouch to the small intestine. This means there is a large portion of the stomach that does not get involved during the digestion process. Once the procedure is completed, food eaten will go into the smaller pouch that was created, bypassing the other larger section of the stomach, and go right into the intestines. Because there is less room in the stomach, patients feel full faster and eat less causing weight loss over time. (Lupoli R, et al.)

Gastric bypass is used when diet and exercise have not helped to reach weight loss goals and the weight poses a large health risk to the patient. Drug treatment for obesity usually leads to a maximum of 15% of weight loss from baseline, but these effects do not last long. After about 1-5 years of weight loss from drug treatment, most patients gain the weight back and sometimes even greater than the baseline. Bariatric surgery has been proven to achieve greater weight loss and more importantly, have a lasting effect. Bariatric surgery is associated with a 42% reduction of CV disease and 30% decrease of all-cause mortality. All bariatric surgery, including gastric bypass, alters the anatomy and physiology of the GI tract causing deficiencies of nutrient absorption in some form. (Lupoli R, et al.)

There are a number of vitamin deficiencies that become evident during the first 4-6 weeks after bariatric surgery. This includes deficiencies in thiamine, riboflavin, folate, vitamin B12, and the fat soluble vitamins A,D,E, & K. Several studies have been conducted that confirm these nutrient deficiencies in patients who have undergone gastric bypass. The deficiencies can cause long term complications that could potentially offset the benefits of the surgery. It is important that patients are followed up after surgery to ensure that these deficiencies are not causing complications that can be avoided with vitamin supplementation. (Çalapkorur S, Küçükkatırcı H)

According to the American Society of Hematology, people who have gone through bariatric surgery show the highest risk of anemia. Anemia usually presents as fatigue, weakness, and cold extremities. 33%-49% of patients present with anemia 2 years after bariatric surgery. With gastric bypass specifically, it is 45-50% of patients. It’s important to note that many patients may have anemia prior to surgery, and it is recommended that patients be screened for this before undergoing surgery. Anemia post surgery is due to low iron as well as B12 deficiency as a secondary cause. There is decreased iron and B12 absorption because the duodenum and proximal jejunum are bypassed, which are the main sites of absorption. There is also a noted change in food preference, such as intolerance for meat and dairy products after the surgery. Folic acid deficiency can also contribute to anemia. Folate is absorbed primarily through the small intestine which is still intact after gastric bypass, so the deficiency is usually because of the shortage of dietary intake rather than non-absorption. (Lupoli R, et al)

Overall, there are a multitude of effects that can occur due to nutritional deficiencies after bariatric surgery which are significantly present in gastric bypass. They may present differently and health-care providers may confuse presentations with other disease states. In patients who have received gastric bypass, it is important to get a history and to be aware that symptomologies may be due to nutrient deficiencies.

References:

1. Lupoli R, Lembo E, Saltalamacchia G, Avola CK, Angrisani L, Capaldo B. Bariatric surgery and long-term nutritional issues. World J Diabetes. 2017;8(11):464-474. doi:10.4239/wjd.v8.i11.464

2. Çalapkorur S, Küçükkatirci H. Vitamin deficiencies and prevention methods after bariatric surgery. Mini-invasive Surgery. https://misjournal.net/article/view/3376#Cite_This_Article. Published March 11, 2020. Accessed December 9, 2021.

3. Gastric Bypass (roux-en-Y). Mayo Clinic. https://www.mayoclinic.org/tests-procedures/gastric-bypass-surgery/about/pac-20385189. Published October 17, 2020. Accessed December 9, 2021.

4. Seeras K, Acho RJ, Lopez PP. Roux-en-Y Gastric Bypass Chronic Complications. [Updated 2021 Jul 26]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK519489/

5. Bariatric surgery procedures: ASMBS. American Society for Metabolic and Bariatric Surgery. https://asmbs.org/patients/bariatric-surgery-procedures. Accessed December 9, 2021.

Common Name/Scientific Name:

Turmeric, Haldo (North India), Manjal (South India),

Curcuma, Curcumin

What is it used for?

Turmeric, sometimes known as the “golden spice” is used for various things such as food spice, medicine, and even cosmetic use. It is what gives curry its yellow color and atypical flavor. It can be found in manufactured food products including canned beverages, dairy, baked goods, juices, cereals, and sauces. In traditional medicine, turmeric is believed to have medicinal properties such as giving the body energy, regulating menstrual periods, treating arthritic pain, and even helping to dissolve gallstones. Many countries in South Asia use turmeric as an antiseptic and as an anti-inflammatory agent. In India, turmeric paste is made and put on the skin of the bride and groom during traditional weddings. This practice is thought to keep harmful bacteria away from the bride and groom during their wedding day as well as make their skin glow.

How does it work?

Modern medicine has shown that turmeric is an antioxidant, anti-inflammatory, antimutagenic, antimicrobial, and anticancer agent. Some studies have shown that a certain level of turmeric ingestion is capable of providing antioxidant protection throughout the body. This antioxidant activity protects the body from free radicals, causes an increase in antioxidant enzyme levels, and inhibits the peroxidation of lipids.

What are some side effects?

There are few reported side effects of turmeric. It is generally safe in large amounts. Some reported side effects during trials using turmeric were diarrhea, headache, rash, and yellow stool. The patients reporting these side effects were receiving between 500 mg -12,000 mg of turmeric in a dose-response study.

Are there any trials that support its use/non-use (efficacy)? Provide details.

There are preventative and therapeutic studies of turmeric in animal models. In a study done to evaluate turmeric’s role in inhibiting chemical carcinogenesis in rats, it was found that turmeric extract helped to protect against genomic damage. In another study where a few fruits and vegetables were tested for their effectiveness in preventing dimethylbenz[a]anthracene (DMBA)-initiated and croton oil-promoted skin tumors, it was found that turmeric was the most potent nutraceutical used as the average number of tumors forms were significantly less than the others tested.

Additional Considerations (Can include known drug interactions, special directions, etc.)

The benefits of turmeric are mostly achieved through ingestion in food. A solid understanding of proper dosing, safety, and mechanism of action is not available for this supplement, as there have been no clinical trials to test it.

References:

1. Prasad S, Aggarwal BB. Turmeric, the Golden Spice: From Traditional Medicine to Modern Medicine. In: Benzie IFF, Wachtel-Galor S, editors. Herbal Medicine: Biomolecular and Clinical Aspects. 2nd edition. Boca Raton (FL): CRC Press/Taylor & Francis; 2011. Chapter 13. Available from: https://www.ncbi.nlm.nih.gov/books/NBK92752/#

2. Kotha RR, Luthria DL. Curcumin: Biological, Pharmaceutical, Nutraceutical, and Analytical Aspects. Molecules. 2019;24(16):2930. Published 2019 Aug 13. doi:10.3390/molecules24162930

Common Name/Scientific Name:

Elderberry/Sambucus Negra

What is it used for?

Elderberry has been traditionally used as alternative medicine to prevent and treat respiratory sicknesses such as the cold or flu. It has been sold over the counter for years and is given commonly to younger children who cannot take common cold medications such as ibuprofen or acetaminophen.

How does it work?

Elderberry contains a compound called anthocyanin, which is part of the overarching category of flavonoids that have possible anti-inflammatory effects. These anthocyanins attach to viral glycoproteins that allow the virus to enter host cells. By binding to the glycoproteins, the anthocyanins render the glycoprotein ineffective therefore not allowing the virus to enter the host cell. Elderberry may also influence the immune system via cytokines. It has been reported that elderberry may increase the production of inflammatory cytokines but also may reduce cytokine production.

What are some side effects?

Though elderberry is known to have beneficial effects the raw berries themselves can be poisonous and cause stomach problems. These stomach problems are caused by lectins that exist in small amounts of the bark, unripe berries, and seeds of elderberry. The actual berry must be cooked before it can be eaten. There is an estimated 3 mg of cyanide in about 100 grams of fresh elderberries, but this is not enough to be a fatal dose to a 60 kg person. Even so, elderberry that is sold or contained in any products commercialized do not contain this small amount of cyanide.

Are there any trials that support its use/non-use (efficacy)? Provide details.

There was a recent systematic review done to see if elderberry had any benefits or harms in treatment of viral respiratory infections, specifically analyzing the relationship of the inflammatory cytokines. 1187 records were screened that included 5 randomized trials on elderberry for the treatment or prevention of viral respiratory diseases. There were no studies that showed a clinical link to the use of elderberry, but there were 3 studies that looked at the production of cytokines after elderberry ingestion. The results from this study conclude that Elderberry may reduce the risk of developing a cold or lessen the severity. It may also reduce the severity of symptoms of influenza. There is no solid evidence for the use of elderberry and no evidence that it overstimulates the immune system in terms of cytokines.

References:

1. Wieland LS, Piechotta V, Feinberg T, et al. Elderberry for prevention and treatment of viral respiratory illnesses: a systematic review. BMC Complement Med Ther. 2021;21(1):112. Published 2021 Apr 7. doi:10.1186/s12906-021-03283-5

2. Mandl E. The pros and cons of elderberry. Healthline. https://www.healthline.com/nutrition/elderberry#risks-and-side-effects. Published March 12, 2021. Accessed January 28, 2022.

Green tea

Scientific Name: Camellia sinensis

Common Name: Green tea; Green Tea Extract; Tea

What is it used for?

Tea is arguably the most well-established and popular beverages with an extensively rich history dating back several millennia. What’s interesting is that the white, green, black, and oolong varieties all come from the same tea plant; the main difference between them is how they are harvested and stored and then ultimately processed. Green tea specifically is made by heating the green tea leaves directly after harvesting, usually through steaming, pan-frying, and drying, in order to halt the oxidation process and keep the tea leaves that bright green color. This gives green tea that fresh-picked flavor profile and is also the reason behind its many touted health benefits. Green tea has been purported to support mental alertness, relieve digestive symptoms, relieve headaches, and promote weight loss. It is also a potential candidate in the fight against cancer and heart disease as some state that its various components are able to delay and/or prevent these late-stage diseases. Moreover, “evidence from clinical trials suggests that green tea plays a role in metabolic syndrome because it may have an impact on body weight, glucose homeostasis, and other cardiovascular risk factors.” Additionally, there’s interest in its potential ability to prevent strokes, COPD, and UV damage. Lastly, there is an FDA-approved preparation called Veregen (sinecatechins) ointment that is indicated for the treatment of external genital and perianal warts in immunocompetent patients 18 years and older; it was first approved back in 2006.

How does it work?

To understand how green tea is potentially a remedy for all these diseases, we have to understand its complex chemical composition. The reason for its complexity lies within the fact that there are numerous components and factors that play a role in the formation of its chemical composition from maturation to harvest to processing. In essence, tea leaves contain a myriad of polyphenols in different quantities as well as caffeine, theanine, theobromine, theophylline, phenolic acids, minerals, and trace elements. Of the polyphenols, there exists also catechins, which play an essential role in preventing cell damage through various mechanisms. Not only that, but there also exists tannins, essential oils, riboflavin, niacin, folic, ascorbic, pantothenic, malic, and oxalic acids, all of which play a role in healthy body functions. There are, in total, more than 2,000 chemicals identified so far in green tea and the really important ones are the catechins, such as (-)-epigallocatechin-3-gallate (EGCG). These catechins are thought to be largely responsible for the aforementioned health benefits as they act as potent antioxidants. Their role as antioxidants are to essentially scavenge for free radicals in the body that cause DNA damage via reactive oxygen species. Moreover, these polyphenols are shown to inhibit tumor cell proliferation, induce apoptosis in laboratory and animal studies, inhibit angiogenesis, reduce tumor cell invasiveness, protect against UVB radiation, modulate immune system function, and provide detoxification enzymes, such as GST and quinone reductase. All of these characteristics are attributed to the potent antioxidant effects of tea, however, the precise mechanisms of action are still yet to be laid out.

What are some side effects?

· Excess intestinal gas

· Nausea

· Heartburn

· Stomach ache

· Abdominal pain

· Dizziness

· Headache

· Muscle pain

· Tachycardia

· Palpitations

· Insomnia

· Restlessness

· Nervousness

· Tremors

· Diarrhea

· Diuresis

· Dry mouth

· Nocturia

· Light-headedness

· Sore throat

· Increased appetite

Are there any trials that support its use/non-use (efficacy)? Provide details.

· A double-blind interventional trial involving 59 people with leukoplakia showed that 3 grams of mixed tea product given both orally and topically for 6 months elicited a partial regression in oral lesions in 38% of the participants, as compared to 10% in the placebo group

o There was also a lower percentage of patients with an increase in lesion size at the end of study

o Another study with 39 people showed no differences in response between green tea extract and placebo

· Two trials showed the effect of tea on a biomarker of oxidative DNA damage

o 8-hydroxydeoxyguanosine (8-OHdG) is a predictor of increased cancer risk and is especially concentrated in breast, lung, liver, kidney, brain, stomach, and ovarian tumor tissue

o One trial with 133 adult heavy smokers showed that green tea reduced urinary 8-OHdG levels by 31% while black tea had no change

o Another trial with 124 patients with hepatitis B and aflatoxin exposure showed that green tea reduced urinary 8-OHdG levels significantly after 3 months

o However, it’s inconclusive whether or not 8-OHdG levels are definitely linked to cancer risk

· A double-blind, placebo-controlled study with 60 men at increased prostate cancer risk showed that fewer prostate cancers were detected in the green tea extract group compared to placebo

o However, two other uncontrolled trials found no evidence of such a reduction

· Other trials with different other cancers also showed inconclusive or clinically ambiguous results

Green tea has been widely used in all regions of the world for thousands of years and many people correlate it to increased longevity. To some extent, there is definitely a potential for green tea to be helpful in all of these aspects; however, it is held back by improper study designs and the still explored and ambiguous realm of cancer risk identification. Though it’s relation to cancer is inconclusive presently, green tea is still very safe to consume as a beverage with most adverse effects only present in oral supplements and extracts. More than that, one could argue that there really is no harm in drinking green tea due to its non-existent toxicology and adverse reaction profile, with only the upside to consider in potential cancer risk prevention. Professionally speaking, I cannot either recommend or not recommend green tea for any medical purposes but it still is and will remain to be a very popular and great tasting beverage for the masses.

References:

1) Bettuzzi S, Brausi M, Rizzi F, et al. Chemoprevention of human prostate cancer by oral administration of green tea catechins in volunteers with high-grade prostate intraepithelial neoplasia: A preliminary report from a one-year proof-of-principle study. Cancer Research 2006; 66(2):1234–1240.

2) Cabrera C, Giménez R, López MC. Determination of tea components with antioxidant activity. Journal of Agricultural and Food Chemistry 2003; 51(15):4427–4435.

3) Choan E, Segal R, Jonker D, et al. A prospective clinical trial of green tea for hormone refractory prostate cancer: An evaluation of the complementary/alternative therapy approach. Urologic Oncology: Seminars and Original Investigations 2005; 23(2):108–113.

4) Chow HH, Hakim IA, Vining DR, et al. Effects of dosing condition on the oral bioavailability of green tea catechins after single-dose administration of polyphenon E in healthy individuals. Clinical Cancer Research 2005; 11(12):4627–4633.

5) Chow HS, Cai Y, Hakim IA, et al. Pharmacokinetics and safety of green tea polyphenols after multiple-dose administration of epigallocatechin gallate and polyphenon E in healthy individuals. Clinical Cancer Research 2003; 9(9):3312–3319.

6) Elmets CA, Singh D, Tubesing K, et al. Cutaneous photoprotection from ultraviolet injury by green tea polyphenols. Journal of the American Academy of Dermatology 2001; 44(3):425–432.

7) Hakim IA, Harris RB, Brown S, et al. Effect of increased tea consumption on oxidative DNA damage among smokers: A randomized controlled study. Journal of Nutrition 2003; 133(10):3303S–3309S.

8) Hamajima N, Tajima K, Tominaga S, et al. Tea polyphenol intake and changes in serum pepsinogen levels. Japanese Journal of Cancer Research 1999; 90(2):136–143.

9) Henning SM, Niu Y, Lee NH, et al. Bioavailability and antioxidant activity of tea flavanols after consumption of green tea, black tea, or a green tea extract supplement. American Journal of Clinical Nutrition 2004; 80(6):1558–1564.

10) Jatoi A, Ellison N, Burch PA, et al. A phase II trial of green tea in the treatment of patients with androgen independent metastatic prostate carcinoma. Cancer 2003; 97(6):1442–1446.

11) Lambert JD, Yang CS. Mechanisms of cancer prevention by tea constituents. Journal of Nutrition 2003; 133(10):3262S–3267S

12) Li N, Sun Z, Han C, Chen J. The chemopreventive effects of tea on human oral precancerous mucosa lesions. Proceedings from the Society of Experimental Biology and Medicine 1999; 220(4):218–224.

13) Luo H, Tang L, Tang M, et al. Phase IIa chemoprevention trial of green tea polyphenols in high-risk individuals of liver cancer: Modulation of urinary excretion of green tea polyphenols and 8-hydroxydeoxyguanosine. Carcinogenesis 2006; 27(2):262–268.

14) Seeram NP, Henning SM, Niu Y, et al. Catechin and caffeine content of green tea dietary supplements and correlation with antioxidant capacity. Journal of Agricultural and Food Chemistry 2006; 54(5):1599–1603.

15) Steele VE, Kelloff GJ, Balentine D, et al. Comparative chemopreventive mechanisms of green tea, black tea and selected polyphenol extracts measured by in vitro bioassays. Carcinogenesis 2000; 21(1):63–67.

16) Tsao AS, Liu D, Martin J, et al. Phase II randomized, placebo-controlled trial of green tea extract in patients with high-risk oral premalignant lesions. Cancer Prevention Research 2009; 2(11):931–941.

17) Wang LD, Zhou Q, Feng CW, et al. Intervention and follow-up on human esophageal precancerous lesions in Henan, northern China, a high-incidence area for esophageal cancer. Gan To Kagaku Ryoho 2002; 29(Suppl 1):159–172.

Aloe vera

Scientific Name: Aloe barbadensis Miller; Aloe ferox Miller (Cape aloe); Aloe perryi Baker (Zanzibar or Socotrine aloe); Aloe vera L.; Aloe vera Miller; Aloe vera Tournefort ex Linne; Aloe vulgaris Lamark (Curacao or Barbados aloe)

Common Name: Aloe vera; Aloes; Barbados; Cape; Curacao; Socotrine; Zanzibar

What is it used for?

Aloe vera is a plant that has stood the test of time through the millennia as a so-called “plant of immortality” due to its myriad of health benefits and uses. It was highly praised in Egyptian medicine and in the entire Mediterranean world as a cure-all for infections, skin treatment, and drug preparation, even body preparation for funerals as it was used to prepare Jesus Christ’s body. Greek physicians note that it was used to heal wounds, stop hair loss, treat genital ulcers, and help with hemorrhoids. Nowadays, it’s used topically for acne, lichen planus, oral submucous fibrosis, burning mouth syndrome, burns, and radiation-induced dermatitis. It’s also available in oral capsules for weight loss, diabetes, hepatitis, and IBS. Moreover, there’s clinical research that suggest its use in speeding up the healing process for burn wounds, relieving pain on cutaneous wounds, helping with herpes simplex and psoriasis. To add on, there’s even juice made from aloe vera pulp and it’s also considered as a laxative to relieve constipation or to cleanse the system. There is also an approved indication for metabolic syndrome and the dosage is 500 mg twice daily for 8 weeks.

How does it work?

The biologically active components in aloe vera are a mixture of water-soluble anthraquinone glycosides called aloin. Allantoin is the primary mucilaginous component in aloe and it serves as a proliferating agent; to add on, there are numerous other compounds such as tannins, polysaccharides, organic acids, enzymes, vitamins, and steroids which all play a role in the effects that aloe vera has. The most important factor in the pain relief that’s provided is a chemical called bradykininase; this is an enzyme that breaks down bradykinin, which plays a crucial role in promoting inflammation. Therefore, by breaking down bradykinin, the inflammation process that causes pain and swelling at a site will be effectively reduced. Aloin elicits the laxative effect as it irritates the GI tract in order to produce movement. Additionally, aloe emodin is a hydroxyanthraquinone that has been studied for its use in inhibiting tumor cell growth in cultures and animal models in vitro. Aloe vera gel is obtained by crushing the leaf of the plant and it usually doesn’t contain the medicinal properties of the anthraquinone glycosides, but it does contain more polysaccharides, especially glucomannan. Glucomannan is similar to guar gum and it contributes to the emollient properties of aloe as a skincare product. There is much to learn about aloe as it has 75 potentially active constituents that all serve a beneficial purpose.

What are some side effects?

Topical

· Burning

· Itching

· Eczema

· Contact dermatitis

· Erythema

· Edema

· Delayed wound healing (1 case)

Oral

· Bloody diarrhea

· Abdominal cramps

· Abdominal pain

· Acute hepatitis

· Tumors in rats (more research is needed for this)

· Bloody diarrhea

· Potassium depletion

· Albuminuria

· Hematuria

· Muscle weakness

· Weight loss

· Cardiac effects

· Hemorrhagic gastritis

· Nephritis

· Acute renal failure

· Acute hepatitis

Are there any trials that support its use/non-use (efficacy)? Provide details.

· Aloe vera has been shown to provide topical relief from inflammation and burns due to its bradykininase activity

· Aloe emodin selectively inhibited human neuroectodermal tumor cell growth in tissue cultures and animal models in vitro

o It is also useable in neuroblastomas, Ewing sarcomas, Merkel cell carcinomas, and fibrosarcomas

· Three trials studied the effect of aloe vera on IBS with 236 total patients; one trial showed a benefit while the remaining two trials showed no correlation

· An European study with 44 adults diagnosed with ulcerative colitis showed that aloe vera twice daily for a month improved symptoms for up to 50% of the patients

o However, 14% of those treated with placebo were also classified as responders

o Could be some confounding factor that influenced both groups

· Aloe vera has been studied in diabetic foot ulcers and dental plaque but there’s no conclusive evidence as of now

· Aloe vera was studied in a double-blind, placebo-controlled trial where it was inserted into a hydrophilic cream base and applied 3x daily for 4 weeks to 60 patients with moderate psoriasis

o At end-of-treatment, the aloe vera group had a 83.3% positive response as compared to the placebo group with 6.6% positive response

o This positive result in psoriatic patients was observed in another study of 41 patients as well

o However, these trials don’t carry enough power to significantly conclude and establish aloe vera’s use in psoriasis as there are conflicting results as well

Aloe vera is a reputable organic alternative for topical sunburn treatment along with numerous other potential benefits in the skincare field. A lot of what it’s beneficial for has to do with the complex make-up of aloe vera with 75 active constituents that could potentially garner a positive impact on the body and skin systems. Though there are conflicting results and data in terms of the antibacterial/anti-infective, anticancer, anti-inflammatory, diabetes, IBD, psoriasis, and wound healing effects, numerous small scale studies have shown that there is at least some hope for its use in all of these fields. There just needs to be a more thorough study of how these mechanisms interact and play together to produce the beneficial result. As shown from these same studies, oral aloe vera might not be a very good choice for use as it can cause some very debilitating cases of adverse events, although they have only been sparse case reports as of date. However, the fact that there are case reports means that these occurrences cannot be ignored, even in the smallest percentage of chance. On a good note, topically applied aloe vera shows little to none adverse effects and is still effective as an emollient if nothing else. More research is definitely needed into this millennia-year old herbal remedy as it does show a lot of promise.

References:

1) Aloe. Natural Medicines website. Accessed at naturalmedicines.therapeuticresearch.com on October 14, 2019. [Database subscription].

2) Choi HC1, Kim SJ, Son KY, Oh BJ, Cho BL. Metabolic effects of aloe vera gel complex in obese prediabetes and early non-treated diabetic patients: randomized controlled trial. Nutrition. 2013;29(9):1110-1114.

3) Fifi AC, Axelrod CH, Chakraborty P, et al. Herbs and spices in the treatment of functional gastrointestinal disorders: a review of clinical trials. Nutrients. 2018;10(11):E1715.

4) Long V. Aloe vera in dermatology—the plant of immortality. JAMA Dermatology. 2016;152(12):1364.

5) National Institute of Environmental Health Sciences. NTP Speaks About Aloe Vera. https://www.niehs.nih.gov/news/newsroom/interviews/aloevera/index.cfm. Accessed on June 24, 2020.

6) National Toxicology Program. Toxicology and carcinogenesis studies of a nondecolorized whole leaf extract of Aloe barbadensis Miller in F344/N rats and B6C3F1 mice (drinking water study). August 2013.

7) Norman G, Christie J, Liu Z, et al. Antiseptics for burns. Cochrane Database of Systematic Reviews. 2017(7):CD011821. Accessed at www.cochranelibrary.comon October 31, 2019.

8) Quezeda SM, Briscoe J, Cross RK. Complementary and alternative medicine. Inflammatory Bowel Diseases. 2016;22(6):1523-1530.

9) Rodriguez S, Dentali S, Powell D. Aloe vera. In: Coates PM, Betz JM, Blackman MR, et al., eds. Encyclopedia of Dietary Supplements. 2nd ed. New York, NY: Informa Healthcare; 2010:7-14.

10) Suksomboon N, Poolsup N, Punthanitisarn S. Effect of aloe vera on glycaemic control in prediabetes and type 2 diabetes: a systematic review and meta-analysis. J Clin Pharm Therap. 2016;41:180-188.

11) Yeh GY, Eisenberg DM, Kaptchuk TJ, Phillips RS. Systematic review of herbs and dietary supplements for glycemic control in diabetes. Diabetes Care. 2003;26(4):1277-1294.