NUTRITIONAL SUPPLEMENTS 101 (EVIDENCE-BASED)

THERE ARE HUNDREDS OF SUPPLEMENTS! HOW SHOULD WE ORGANIZE THEM?

There are literally HUNDREDS of nutritional supplements out there, which means it’s easy to get overwhelmed with all of the options available. I’ve found it helps tremendously to have an organized system to categorize supplement options. Here’s how I organize nutritional supplements…


DIGESTIVE SYSTEM SUPPORT SUPPLEMENTS How important is the digestive system to overall health? For starters, of all the essential nutrients needed by the body (including 9 essential amino acids, 2 essential fatty acids, 14 essential vitamins and 14 essential minerals) all but ONE come solely from the beverages we drink, supplements we take and food we eat, via the digestive system. And even with that exception (vitamin D, which can be obtained from sunshine) our diet can still supply that nutrient as well. But remember- "You're not what you eat, you're what you ABSORB." Oftentimes a successful move toward improved physical health starts with a smart, personalized nutritional protocol that focuses on restoring and optimizing digestive system health. Nutritional supplements can play a major role in these efforts.



We should also note that gut health is directly linked to the health of several other body systems, including the immune system (as roughly 70% of the immune system resides in the gut lining and flora) and the nervous system (as 50% of dopamine and 90% of serotonin, two major neurotransmitters, are synthesized in the gut). Finally, the health of the gut has been scientifically linked to 90% of the diseases we’re burdened with here in the United States! [30-32]


So what are some of the more significant digestive system supplements?


STOMACH SUPPORT SUPPLEMENTS

For the stomach, notable supplements here include enzymes and betaine HCL. Enzymes help break down macronutrients so they are more easily absorbed, whereas betaine HCL increases hydrochloric acid levels in the stomach. [33-35]


INTESTINAL SUPPORT SUPPLEMENTS

For the intestines and gut flora, notable supplements here include…


* Probiotics (by increasing beneficial bacteria and yeast in the gut, probiotics improve digestion and absorption of nutrients, drive down inflammation in the gut and body, and improve immune system functioning) [36-37]


* Prebiotic fibers (which help “feed” healthy gut flora) [38]


* Functional fibers like Psyllium (which improve bowel regularity and effective elimination of waste materials) [39]


* Magnesium (which, among several benefits, helps relax soft tissues to improve bowel regularity) [40]


* and Glutamine (an amino acid that’s been shown to help heal the intestinal lining). [41]


LIVER & GALLBLADDER SUPPORT SUPPLEMENTS

For the liver and gallbladder, notable supplements here include milk thistle extract (i.e. silymarin) as well as TUDCA and ox bile. These supplements improve digestive health and the liver’s detoxification efforts by improving liver cell functioning and by increasing the amount of bile available in the duodenum. [42-47]



KIDNEY SUPPORT SUPPLEMENTS

For the kidneys and renal system, notable supplements here include potassium citrate and apple cider vinegar. In addition to its proven kidney-supporting benefits, potassium, an essential major mineral and electrolyte, also helps combat hypertension (which is the leading cause of cardiovascular disease, the top killer of adults). Apple cider vinegar, high in acetic acid, has also been shown to improve blood sugar levels and promote healthy weight loss. [48-49]



MACRONUTRIENT SUPPORT SUPPLEMENTS

(AMINO ACIDS, FATTY ACIDS & CARBS)

After digestive system support, we then move on to essential and therapeutic macronutrients not already discussed. Remember, macronutrients include proteins, fatty acids and carbohydrates.


Notable protein and amino acid supplements include…


* Grass fed whey protein, which helps support muscle maintenance and growth [50-51]


* Collagen peptides types 1, 2 and 3, which are important for skin, bone and joint health [52-56]


* L-lysine, an amino acid that’s been shown to be effective against the herpes virus [57-58]


* 5-HTP, a form of tryptophan and a proven sleep aid and anti-anxiety supplement [59-60]


* Citrulline, which has been shown to increase nitric oxide levels and improve blood flow [61-62]


* Tyrosine, an amino needed for thyroid health and also shown to improve symptoms of depression [63-64]


* L-theanine, which has been shown to improve sleep, cognition and anxiety symptoms [65-69]


* Creatine, a rigorously studied compound proven to help build and maintain muscle mass & strength [70-74]


* and GABA, a neurotransmitter shown to improve sleep quality and reduce symptoms of anxiety. [75-76]



Notable fatty acid supplements include high EPA and DHA fish oils as well as MCT and coconut oils.


EPA and DHA omega 3 fatty acids are proven anti-inflammatory agents and exert positive effects on the cardiovascular and nervous systems and have also been shown to effectively combat conditions like obesity, arthritis and eye diseases. [77-83]



Coconut oil and medium chain triglycerides (MCTs) are neuroprotective and antimicrobial fatty acids that have also been scientifically shown to improve exercise performance and increase metabolism while promoting weight loss. [84-89]


Notable therapeutic carbohydrate supplements include d-ribose, which has a proven clinical track record for treating cardiovascular disease, chronic fatigue and fibromyalgia. [90-92]

MICRONUTRIENT (VITAMIN & MINERAL) SUPPORT SUPPLEMENTS

After macronutrients, we shift into coverage of the essential and therapeutic micronutrients not already discussed. This includes…


Water soluble vitamins such as the 8 essential B vitamins and vitamin C.


The 8 B vitamins include vitamins B1, B2, B3, B5, B6, B7, B9 and B12. All 8 B vitamins play a role (either directly or indirectly) in energy levels and all 8 are also essential for nervous system health. [93]


For instance, studies have shown that…


* Vitamin B1 (thiamine) helps combat diabetic and peripheral neuropathy [94]


* Vitamin B2 (riboflavin) is effective against migraines [95]


* Vitamin B3 (niacin, specifically nicotinic acid) improves overall nervous system health and mood [96]


* Vitamin B6 (pyridoxine) has benefit for mood conditions like depression [97]


* Vitamin B7 (biotin), in very high doses, may have benefit against conditions like Multiple Sclerosis [98]


* Vitamin B9 (folate) helps improves neurological functioning and reduces the risk of neural tube defects in babies [99]


* And Vitamin B12 (cobalamin) which is effective against nerve pain and reduces the risk of Alzheimer’s and dementia. [100]


In addition to energy and nervous system benefits, several B vitamins have other proven health benefits. For example…


* Vitamin B3 is linked to improved cardiovascular and skin health [101-102]


* Vitamin B5 has been shown to cause dramatic improvement in skin conditions like acne [103]


* Vitamin B7 is well known for its positive effects on hair and nail health [104-105]


* And Vitamin B9 is linked to a lower risk of cardiovascular disease and cancer. [106]


I often recommend a B complex supplement that contains therapeutic levels of all 8 essential B vitamins, in forms that are the most bioavailable to the body (for example, 5-MTHF versus folic acid).



Choline is an essential micronutrient that’s often categorized along with the B vitamins, although therapeutic doses of choline are generally much greater than the other B vitamins. Choline assists in the emulsification of fats (i.e. breaking down dietary fat into its constituent parts) and protecting the liver from an abnormal accumulation of fat and cholesterol, such as is the case with conditions like Non-Alcoholic Fatty Liver Disease (NAFLD).


While choline is found in relatively high amounts in supplements like sunflower lecithin, other forms of choline are commonly used to improve brain performance. Supplements here include Alpha GPC (glyceryl-phosphoryl-choline), citicoline (i.e. CDP or cytidine-diphosphate-choline) and choline L-bitartrate. These supplements tend to work by optimizing the levels and functioning of acetylcholine, which as the first neurotransmitter ever discovered. [107-115]



Vitamin C is another water soluble vitamin that’s well known for its immune system benefits, which has implications for both infectious diseases like COVID and the flu as well as cancer. Dozens of scientific studies have also highlighted vitamin C’s positive effects on the cardiovascular system, adrenal health, wound healing and collagen production. [116-117]



After the water-soluble vitamins comes fat-soluble vitamins like vitamins A, D, E and K.


Vitamin A comes from two sources- retinoids (which includes retinol and comes from animal sources) and carotenoids (which includes beta carotene and comes from plants). Vitamin A plays a vital role in immunity (which has implications for cancer as well as infectious diseases) as well as skin health and eyesight. [118-121]


Vitamin D is an essential fat soluble vitamin that’s unique in that it often acts more like a hormone than a vitamin in the body. Studies have shown that 40-80% of Americans are deficient in vitamin D. Vitamin D3 plays a major role skeletal health (i.e. bones and teeth), immunity, endocrine (hormonal) health and cardiovascular health and has benefit for several common conditions including osteoporosis, joint pain, cancer, COVID, influenza, gastrointestinal disorders, mood disorders, atherosclerosis and sleep. [122-124]


Vitamin E is a group of 8 compounds that includes 4 tocopherols and 4 tocotrienols. Vitamin E has proven antioxidant effects and has positive effects on the cardiovascular system as well as skin and eye health. [125]


Vitamin K actually includes two separate groups- vitamin K1 or phyllo-quinone and vitamin K2 or mena-quinones, of which there are several, including MK-4, 7, 8 and 9. While vitamin K1 is somewhat well known for its role in blood clotting, vitamin K2 is gaining more recognition for its role in skeletal and cardiovascular health, as it helps shuttle calcium into the bones and teeth and out of the soft tissue, where it can contribute to atherosclerosis. [126]



After the essential vitamins comes minerals not yet discussed, including major minerals (electrolytes) such as calcium. Much of the research on calcium supplementation is conflicting and controversial. While some studies show that certain forms of calcium supplementation improve bone density levels, other studies have shown few skeletal benefits but have highlighted an increased risk of cardiovascular disease, kidney stones and gastrointestinal upset. I generally suggest most adults try to obtain their calcium through hypoallergenic food sources such as goat or sheep’s milk cheeses or organic Greek yogurt, or that they consider a more bioavailable form of calcium supplementation such as calcium phosphate. [127-129]



After the major minerals come the 8 essential trace minerals. Some of the more notable micronutrients here include iodine, iron, selenium and zinc.



Speaking of iodine, the body needs iodine to produce thyroid hormones, which play a major role in overall metabolic health. In children, iodine deficiency can lead to impaired growth and cognitive development. In adults, iodine deficiency is often an underlying cause of hypothyroidism, which commonly leads to low energy, weakness, weight gain, hair thinning and cognitive impairment. [130-133]


Iron is needed to transport oxygen in the blood via hemoglobin. Iron deficiency can cause anemia (as can other factors, such as chronic disease and inflammation). Some common symptoms of iron deficiency include low energy, weakness and mental impairment. Some studies have shown that iron deficiency in children is correlated with impaired growth. Certain types of iron supplements (such as ferrous sulfate) are notorious for causing gastric upset and/or constipation whereas other forms (ferric pyrophosphate and ferrous glycinate for example, also known as “gentle iron”) tend to be better tolerated. Vitamin C (ascorbic acid) helps with iron absorption. [134-143]


In addition to iodine, the thyroid gland also needs selenium to produce thyroid hormones. Selenium also plays a significant role in reproductive health and immunity, and as such has implications for infectious diseases as well as cancer. Even moderate doses (200-400mcg/day) of selenium can slow down a healthy thyroid gland, but for those with Grave’s Disease or Hashimoto’s Thyroiditis, this amount is often very therapeutic. [144-149]


Zinc is a trace mineral that’s necessary for proper immune system, reproductive, digestive and skin health. Therapeutic amounts of zinc (usually 75-100mg/day) have been shown to significantly reduce the risk of several common infectious diseases (including COVID, influenza and the common cold) and adequate intakes are also linked to a decreased risk of several types of cancer. [150-155]


There are a handful of other minerals that some researchers believe should be considered essential even though they haven’t been formally recognized as such yet. These include…



* Boron, which has been shown to improve bone mineral density [156-157]


* Lithium, which has been shown to improve neurological health and is effective against mood conditions like bipolar disorder [158-161]


* Silica, which has been shown to improve both bone and connective tissue health [162-163]


* and Sulfur, which is present in amino acids like methionine and cysteine (as well as supplements like MSM) and has therapeutic benefit for several inflammatory and connective tissue conditions (such as arthritis). [164-166]


​Prioritizing digestive system support along with essential macro and micronutrients mirrors much of what an Orthomolecular approach advocates for, which seeks to emphasize essential macro and micronutrient supplements above other supplements such as botanicals, non-essential antioxidants and certain hormone-supporting supplements.



OTHER ANTI-PARASITIC, ANTI-MICROBIAL & IMMUNE-SUPPORTING SUPPLEMENTS

After covering macro and micronutrients we shift into anti-parasitic, anti-microbial and other immune system supporting supplements. This includes…



Supplements with proven anti-parasitic effects such as wormwood and cloves. [167-171]

Supplements with proven anti-bacterial effects such as garlic oil, oregano oil, colloidal silver, goldenseal root and olive leaf extract. [172-185]


Supplements with proven anti-fungal effects such as caprylic acid and neem. [186-190]


Supplements with proven anti-viral effects such as echinacea and elderberry. [191-196]


And other immune system-supporting supplements such as beta glucan and bovine colostrum. [197-204]


Although they’re not nutritional supplements, with this category I will often mention certain antiparasitic drugs like fenbendazole, ivermectin, praziquantel and pyrantel pamoate with clients who show signs of parasitic infection (or whose labs confirm significant parasitic load). These drugs tend to be highly effective while also possessing a relatively low risk of adverse drug reactions. [205]


OTHER TOXIC METAL CHELATION SUPPLEMENTS

After anti-parasitics, anti-microbials and other immune system support we transition to toxic metal chelators and removers. Supplements here include ALA (which may be contraindicated if dealing with yeast issues) and calcium disodium EDTA.



Although they’re not nutritional supplements, with this category I will often mention chelation drugs like DMSA and DMPS with clients who show signs of metal toxicity (or whose labs confirm metal toxicity). [206-210]

OTHER JOINT-SUPPORTING & PAIN-RELIEVING SUPPLEMENTS

After toxic metal chelators, we next move on to other joint-supporting and pain-relieving supplements. Therapeutic agents here include…


* Kratom [211-213]

* Turmeric extract (curcumin) [214-216]

* CBD oil (shown to be most effective for nerve pain) [217]

* Hyaluronic acid (which has also been shown to improve skin health) [218-220]

* Glucosamine and chondroitin [221-222]

* and White Willow Extract (i.e. salicin). [223]



OTHER ANTIOXIDANT SUPPLEMENTS

After other joint-supporting and pain-relieving supplements we look at other antioxidant supplements. This category includes supplements like…



* Glutathione (which has been clinically shown to positively impact skin, liver and immune system health) [224-227]


* CoQ10 (which has been shown to improve cardiovascular health, mitochondrial functioning and energy levels) [228-230]


* Trans-resveratrol (a polyphenol that studies have shown has cardio-protective, anti-cancer and anti-aging effects) [231-234]


* Lutein (a carotenoid that’s been shown to improve eyesight and effectively combat macular degeneration) [235-238]


* Astaxanthin (another carotenoid antioxidant shown to improve skin health and reduce sensitivity to sun exposure) [239-240]


* and Quercetin (a flavonoid that studies have shown helps treat allergies, respiratory conditions (including COVID) and cancer). [241-244]

OTHER HORMONE-SUPPORTING SUPPLEMENTS

After other antioxidant supplements comes other hormone support supplements, including…



* Pregnenolone (a neuro-steroid and “mother hormone” that studies have shown plays a major role in cognitive functioning, memory and libido, and is often taken to combat symptoms of menopause and fatigue) [245-246]


* DHEA (the most abundant circulating hormone, studies have shown that DHEA supplementation can improve energy, physical performance, combat symptoms of menopause, improve reproductive health, increase libido, and improve hormone profiles (including low testosterone)) [247-250]


* Progesterone cream (one of the chief sex hormones (along with testosterone and estrogen), progesterone has been shown safe and effective for treating infertility, symptoms of menopause and PMS, and emerging data is showing its value against conditions like PCOS and endometriosis) [251-255]


* Inositol (a sugar alcohol, myoinositol has a proven clinical track record for treating infertility and PCOS) [256-260]


* and Vitex Berry (also known as chasteberry, which several studies have shown is effective against PMS). [261-263]


OTHER SUPPLEMENTS

Additional supplement categories can include…


* other blood sugar and insulin supporting supplements such as berberine and cinnamon


* adaptogenic herbs that help combat the effects of stress, such as ashwagandha, rhodiola and panax ginseng


* other cardiovascular supporting supplements such as nattokinase, hawthorne berry and butcher’s broom


* other mood-supporting supplement like mucuna (L-dopa) and St. John’s Wort


* other respiratory-supporting supplements such as bromelain and nettle leaf


* and libido enhancing supplements like tribulus and maca root.


Again, there’s a reason I place the supplement categories in the order I do. Emphasizing digestive system support first helps improve the break down and absorption of nutrients as well as elimination of waste material. Doing this also positively impacts gut and systemic inflammation levels, reduces (to a degree) parasitic and/or pathogenic load levels and positively impacts every other body system, most especially the immune and nervous systems.


Next, I generally consider essential macro and/or micronutrient supplements, with a goal of utilizing those supplements that are likely to have the most positive therapeutic effect, as based on client medical testing and health assessment results.


After utilizing digestive system support and select macro and/or micronutrient supplements for a time (it may be a week or a month, depending on the individual) the body and its pathways of elimination (intestines, liver and kidneys) are usually much more ready to handle the side effects of a detoxification protocol, be it from parasites, pathogenic microbes (including candida) and/or toxic metals (mercury, lead, aluminum, etc.).


While other joint support and pain relief supplements are listed next, I will often recommended one or more of these at the start of a client’s supplement protocol if daily acute or chronic pain is present.


Lastly, the other categories of supplements are also considered.



WHAT TO LOOK FOR IN A SUPPLEMENT

These are some of the criteria I consider when choosing a nutritional supplement…

1. High quality raw materials

2. Materials with a low risk of adverse effects (ex. choosing methyl cobalamin over cyanocobalamin for B12)

3. Therapeutic dosages (ex. 50-100B CFU probiotic over a 5B CFU probiotic)

4. Formulas that increase bioavailability of raw materials (ex. curcumin with piperine vs without piperine)

5. Few if any unnecessary fillers/additives (ex. flow agents, artificial colors, artificial sweeteners, etc.)

6. Strong scientific evidence for efficacy

7. A form conducive for regular consumption (ex. some powders taste awful and are more suitable in pill form)

8. More pronounced effects when compared to other products

9. Produced by reputable company

10. Relatively easy to obtain (ex. available through reliable retailers like Amazon, Vitacost, iHerb, etc.)

11. General preference for natural form vs synthetic (ex. fish oil derived vitamin A vs retinyl palmitate)

12. Standardized extracts generally preferred vs whole herb formulas (ex. 95% curcuminoids turmeric supplement vs non-standardized turmeric)

13. Few if any common allergens (ex. wheat/gluten, GMO corn, soy, etc.)

14. Good value


Labdoor (www.labdoor.com) is an independent company that tests nutritional supplements and is worth looking at before purchasing a new product. Labdoor tests hundreds of supplements to see if products contain what they claim to contain, and if they have any harmful ingredients or contaminants.


I try to consider ALL of the factors above before recommending a product. For example, if a supplement with 1-2 fillers (ex. magnesium stearate, stearic acid, etc.) meets many of the above factors and is significantly cheaper than a similar product with fewer additives and flow agents I may recommend the better value supplement.


SUPPLEMENT DOSAGES

All of the dosage information and suggestions I share are gathered from scientific and clinical data as well as from other professional resources, manufacturers labels and user feedback. Aside from data sourced from clinical literature (PubMed, PMC articles, etc.), I’ve found two online independent sources particularly helpful in their efforts to collate clinical research on supplements. These websites are https://examine.com/supplements/ and https://selfhacked.com/substances/.


Therapeutic amounts vary from person to person and will depend on a variety of factors, including…

* body weight

* pre-existing levels of nutrients and other compounds in the body’s tissues and fluids

* and the overall condition of the body, as well as the condition of certain body systems and tissues.


The complexity of variables involved in creating a safe, effective, personalized nutritional supplement protocol is one reason why it’s helpful to work with a qualified, experienced professional before beginning any nutritional supplement protocol (or if making significant changes to an existing nutritional program).


Once relevant high quality supplements have been selected and therapeutic dosages have been determined, I often suggest that people start by taking most supplements 2 times a day (once in the morning with breakfast and once at night with dinner). I find that this is realistic and doable for most people, even busy professionals with kids. Supplements that increase energy or metabolism


PILLS VS CHEWABLES VS POWDERS VS LIQUIDS

PILLS (capsules, softgels, tablets, chewables, etc.): I generally give preference to supplements in pill form, as I’ve found it’s usually easier for most people to stay consistent with pills as opposed to powders, liquids and other forms. I also tend to recommend pill form if the powder version is taste averse (ex. white willow bark, curcumin, n-acetyl cysteine, etc.) or if convenience is highly preferred over value.


POWDERS: I generally recommended powders when the amount taken to reach therapeutic dosages isn’t very feasible with pills and the powder is not taste averse (ex. glutamine, glycine, whey protein, collagen protein, lysine, high-dose vitamin C, etc.). Powders are also generally a much better value than pills, although often less convenient.


LIQUIDS, SPRAYS, ETC.: I sometimes recommend supplements in liquid form if a suitable pill version can’t be found (ex. raw apple cider vinegar) or if, like powders, the amount needed to reach therapeutic levels isn’t feasible with pills and the liquid isn’t taste averse (ex. MCT oil). I also commonly recommend iodine (Lugol’s) in liquid form, as it tends to be absorbed better than the pill versions.


DAILY ACTION STEPS/SOLUTIONS

Step 1: Start by identifying a few (3-5) supplements that will likely have a significant, positive impact on your health (ideally these are identified through lab/medical testing and/or through working with a knowledgeable healthcare provider). If you’re confused about where to start, I often suggest starting with digestive system (i.e. gut and liver) support.


Step 2: Identify what a starting therapeutic dose will be for each of your supplements. For energy and metabolism-boosting supplements I often suggest taking them once a day, in the morning. For sleep-supporting supplements, especially those that may cause drowsiness, I often suggest taking them once a day, at night. For all other supplements I generally recommend starting with 2 doses a day (one in the morning and one in the evening).


Step 3: Decide on whether it’ll be easier for you to be consistent with either pills or chewables or powders. For most adults (and most supplements) I’ve found that pills (which includes capsules and tablets) are usually the best option. Exceptions here include many protein powders such as whey protein, collagen peptides, glutamine and creatine.


Step 4: Identify some high quality products and purchase. I’ve found I generally save money by going through online retailers like Amazon, Vitacost and iHerb.


Step 5: If you’re consuming pills or chewables you may also consider a weekly pill organizer. I suggest looking for organizer where the individual pill compartments are least 1” x 1” x 1” (and preferably closer to 2” x 1” x 1”).


Step 6: Once you’ve received your supplements and pill organizer, prepare for success by placing your pills in the organizer for the next week.


Step 7: Add or remove supplements and adjust your dosages as needed.


The bottom line here: find the supplements that you can be consistent with, that are sustainable for the long-term (if need be) and that give you the results you want/need.


SOURCES

30 www.ncbi.nlm.nih.gov/pmc/articles/PMC3337124/ (2012; role of gut in immune system functioning)

31 www.ncbi.nlm.nih.gov/pmc/articles/PMC6005194/ (2019; neurotransmitter modulation by gut flora)

32 https://worldmicrobiomeday.com/

33 www.ncbi.nlm.nih.gov/pmc/articles/PMC4923703/ (2016; digestive enzyme supplementation in gastrointestinal diseases)

34 http://archive.foundationalmedicinereview.com/publications/13/4/307.pdf (2008; role of enzyme supplementation in digestive disorders)

35 www.ncbi.nlm.nih.gov/pmc/articles/PMC3946491/ (2013; betaine and re-acidification of stomach to improve digestion & absorption)

36 www.ncbi.nlm.nih.gov/pmc/articles/PMC6306248/ (2018; review found 68% of probiotics reviewed had strong-moderate efficacy for at least 1 type of disease)

37 www.aafp.org/afp/2017/0801/p170.html (2017 review of the evidence for using probiotics for GI conditions)

38 www.ncbi.nlm.nih.gov/pmc/articles/PMC6579922/ (2019 review of IBS, including beneficial effects of prebiotics on gut microbiome)

39 www.ncbi.nlm.nih.gov/pmc/articles/PMC5548066/ (2017 review of fiber & IBS; 14 trials of 900+ IBS patients found psyllium most effective at improving symptoms)

40 www.ncbi.nlm.nih.gov/pmc/articles/PMC3036964/ (2011 review of treatments for chronic constipation, including magnesium sulfate/Epsom salts)

41 www.ncbi.nlm.nih.gov/pmc/articles/PMC5454963/ (2017; glutamine’s impact on intestinal diseases [leaky gut, impacting tight junctions])

42 www.ncbi.nlm.nih.gov/pubmed/30080294 (2018; review of milk thistle & its use with liver diseases)

43 www.ncbi.nlm.nih.gov/pubmed/23592128 (2013; TUDCA effective for reducing liver enzymes, increasing albumin)

44 www.ncbi.nlm.nih.gov/pubmed/9840118 (1998; TUDCA effective at 500-750mg/day for chronic hepatitis)

45 www.ncbi.nlm.nih.gov/pubmed/8541578 (1995; TUDCA is liver protective even at very low doses 10-13mg)

46 www.ncbi.nlm.nih.gov/pmc/articles/PMC4819118/ (2016; the use of animal biles [including ox/cattle/bovine and bear/TUDCA] for liver diseases)

47 www.ncbi.nlm.nih.gov/pubmed/20434968 (2010; bile salts [like ox bile and UDCA] are effective for increasing bile flow in cholestasis)

48 www.ncbi.nlm.nih.gov/pubmed/28762682 (2017; potassium citrate as effective for both preventing & treating kidney stones as well as improving bone mineral density)

49 www.ncbi.nlm.nih.gov/pmc/articles/PMC6642359/ (2019; daily intake of vinegar reduced stone recurrence, increased citrate & reduced calcium in urinary excretion in CaOx stone formers without adverse side effects)

50 www.ncbi.nlm.nih.gov/pmc/articles/PMC4681166/ (2015; whey protein supplementation may increase abdominal fat loss in response to resistance training when compared to carbs)

51 www.ncbi.nlm.nih.gov/pmc/articles/PMC2289832/ (2008; 12 week study showing use of whey protein helps support lean muscle maintenance and fat loss during calorie restriction for weight loss)

52 https://jddonline.com/articles/dermatology/S1545961619P0009X (Jan 2019; review of 11 studies of >800 people using dosages of 2.5-10g/day found that short & long-term use of oral collagen supplements for wound healing & skin aging was beneficial; oral collagen supplements also increase skin elasticity, hydration & dermal collagen density; collagen supplementation is generally safe with no reported adverse events)

53 www.ncbi.nlm.nih.gov/pmc/articles/PMC5793325/ (2018; “SCP (specific collagen peptides) increased BMD (bone mineral density) in postmenopausal women with primary, age-related reduction of BMD. In addition, SCP supplementation was associated with a favorable shift in bone markers, indicating increased bone formation and reduced bone degradation.”)

54 www.ncbi.nlm.nih.gov/pubmed/24852756 (2015; 13 week RCT found collagen peptides potential therapeutic agents for management of osteoarthritis & maintenance of joint health)

55 www.ncbi.nlm.nih.gov/pmc/articles/PMC4731911/ (2016; RCT of 191 people over 180 days; group that received 40mg/day UC-II improved pain, stiffness & physical function when compared to placebo group and glucosamine/chondroitin group)

56 www.ncbi.nlm.nih.gov/pmc/articles/PMC2764342/ (2009; UC-II effective for RA and OA, and is superior to glucosamine & chondroitin for knee OA)

57 www.ncbi.nlm.nih.gov/pubmed/3115841 (1987; 6 month study of 52 ppl with recurring HSV found that group taking lysine 1g 3x/day [3g/day ttl] had 2.4 less HSV infections & symptoms were significantly diminished)

58 www.ncbi.nlm.nih.gov/pubmed/6438572 (1984; 12 month study of 26 ppl with recurring herpes lesions; experimental group that received 1g lysine had significantly fewer lesions than control group; study found when serum lysine >165 nmol/ml herpes lesions decreased)

59 www.ncbi.nlm.nih.gov/pmc/articles/PMC7334763/ (2020 study; “it has been indicated that supplementation of tryptophan (1 g or more) produces an increase in subjective sleepiness and a decreased time to sleep especially in subjects with mild insomnia. A random double-blind experiment on healthy adults suggested that tryptophan consistently reduced sleep latency which is associated with blood levels.”)

60 https://pubmed.ncbi.nlm.nih.gov/3312397/ (1987; 5-htp as serotonin precursor, effective against anxiety disorders)

61 www.ncbi.nlm.nih.gov/pubmed/27252277 (2016; arginine plays a critical role in blood flow, wound healing & T-cell activity)

62 www.ncbi.nlm.nih.gov/pmc/articles/PMC4669336/ (2015; in fasted state, nitric oxide synthesis was 50% lower in older vs younger adults and is related to decreased amount of arginine; 3g citrulline stimulated arginine synthesis in both older adults & to greater extent in young adults)

63 www.ncbi.nlm.nih.gov/books/NBK500006/ (2019; “Thyroid hormones are essential for proper brain function development in infants and metabolic activity regulation in adults, as well as a wide array of effects on every organ system in the body. The main hormones produced by the thyroid gland are thyroxine (T4), triiodothyronine (T3) and reverse triiodothyronine (rT3), and they are controlled by thyroid stimulating hormone (TSH) from the anterior pituitary gland…Within the vesicles (of the thyroid gland), the iodide is oxidized and covalently bound to tyrosine residues via the enzyme thyroid peroxidase. The formation of these covalent bonds forms mono-iodo-tyrosine residues, which are the building blocks of T3 and T4.”)

64 www.ncbi.nlm.nih.gov/pubmed/27403851 (2016; tyrosine improves cognition in stressful environments; “Tyrosine (TYR), the precursor of dopamine (DA), has been shown to enhance facets of cognitive control in situations with high cognitive demands.”)

65 https://pubmed.ncbi.nlm.nih.gov/27396868/ (2017; “Our study suggests that chronic (8-week) l-theanine administration is safe and has multiple beneficial effects on depressive symptoms, anxiety, sleep disturbance and cognitive impairments”)

66 https://pubmed.ncbi.nlm.nih.gov/25759004/ (2015; “200 mg of L-theanine before bed may support improved sleep quality not by sedation but through anxiolysis.”)

67 https://pubmed.ncbi.nlm.nih.gov/31412272/ (2019; “theanine administered at daily doses ranging from 200 to 400 mg for up to 8 weeks are safe and induce anxiolytic (anti-anxiety) and anti-stress effects in acute and chronic conditions”)

68 https://pubmed.ncbi.nlm.nih.gov/31758301/ (2020; “200-400 mg/day of l-theanine may assist in the reduction of stress and anxiety in people exposed to stressful conditions”)

69 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080935/ (2021; L-theanine improve cognition)