Supplements
One of the most common questions I am asked is: “But isn’t there something natural I can take rather than a medicine?” I always have to take a breath, because I usually hear this after 30 minutes of talking about sleep, diet, hydration, electrolytes, and physical therapeutics. I always begin and end that discussion with some variation of “There are definitely some medicines that can help, but at the end of the day they are the least important component of treatment.” However, behavioral measures (sleep, diet, etc…) are much more complex and people do want a simple answer for the visit. When they ask about something “natural”, they mean they want a vitamin or a supplement.
I must start any thorough discussion about supplements by clarifying a few things. Supplements are not always safer than “drugs”. We must always remember that arsenic is very “natural” and very toxic. In fact, the thing that is nice about the “drugs” is that when something is distilled down to roughly one chemical, we know it is much more predictable than herbal treatments. Some historically used supplements have been abandoned by prescribers after the root became cheaper to acquire from a new place in China and suddenly people’s livers decided to fail. It is for this reason we no longer prescribe butterbur for migraine. In some cases, doctors get on board with a presumably safe treatment like fish oil for heart health. Turns out in people with a prior stroke it can reduce the risk, but in people without prior heart disease or stroke it increases the risk! And, of course, dose matters. Many supplements are useful at small doses but higher doses can cause liver failure, like with Turmeric. Since supplement dosing isn’t well regulated, you just have to hope that the batch of Turmeric you bought isn’t accidentally 10x the dose on the bottle. Turmeric is also a good example of a supplement that needs another substance to be effective. Lastly, most supplements that are supported by pop-culture and social media have very little supportive data, since case reports, anecdotes, and poorly controlled studies are prone to the placebo effect. I am absolutely ok with people taking a SAFE supplement that may help, but the placebo isn’t probably worth it if you’re rolling the dice on liver failure.
SO that being said, I tend to give very specific advice about supplements for specific complaints. There are a few conditions like Migraine where most neurologists and some PCPs start with supplements because of pretty good data. Other conditions like neuropathy, joint and muscle pain, and tinnitus have a long list of supplements that have had some data, but in larger studies the data showed it didn’t help much more than placebo (if at all). Many patients would rather I recommend 10 possibly effective supplements, some of which have numerous active chemicals, than to take a medicine. But, taking 10 supplements all at once with a total of 50 potentially active chemicals becomes very expensive and has never been studied for effectiveness or safety.
In this article I will focus on Migraine, Vitamin deficiencies, Tinnitus, and Muscle cramps. Regarding migraine, while a dozen or so supplements have been in vogue at one time or another, currently there are three supplements that are deemed safe and effective for Migraine. Like with the medicines for migraine, they are mostly studied for the headache frequency or severity. However, as a general rule among neurologists (mirrored by my clinical experience), if a treatment helps for the headache, it usually helps for the light sensitivity, the vestibular dysfunction, and other para migrainous features as well. These supplements were never compared to each other, but they are safe to take together because they are very well understood individual chemicals that don’t interact.
Migraine Supplements:
Riboflavin (B2) - better than placebo at 400mg daily.
Magnesium - studied at 400mg daily, also significantly improved migraine over placebo.
Often increases and softens bowel movements, can be disruptive to GI tract
Glycinate more “belly friendly”
Citrate more helpful for constipation
CoQ10 was also well studied at 100mg three times daily (super inconvenient and reasonable to take 300mg daily) and found to be effective. Note, they never compared those doses to higher or lower amounts, or taking it all at once or split dosing.
B2 - turns urine neon orange
It is very important not to just take a mixed migraine supplement without looking at doses, because often they’ll have too little of one or another.
Compared to medicines that often kick in within a week or two, these three supplements all took about 3 months to fully separate from placebo. Supplement trials can be long and it can be difficult to tell if the supplement is helping or not. Luckily, the benefit wears off much quicker, so trialing off of the supplement usually makes it clear if it was helping or not.
Vitamin Deficiencies - The best data comes from treatment of vitamin deficiencies.
Low Vitamin B12 has always been considered to be a contributor to fatigue and cognitive complaints, and blood testing may be unreliable. However, if someone is in the higher range (500 or above) there is likely little usefulness in adding B12.
Vitamin D supplementation, when a blood test shows low vitamin D (usually < 30) has been clearly shown to be useful, but not clearly in patients whose vitamin D is normal.
Lastly, in patients with a gene mutation of the MTHFR gene, a particular supplement called 5-MTHF or methyfolate is often useful for cognitive, mood, and general fatigue components of ME/CFS/Long COVID
Tinnitus is a pretty complex condition, and consequently the supplement recommendations are not “one size fits all”. If Tinnitus is part of a migraine syndrome, I often recommend starting with the above combination (Riboflavin 400mg daily, Magnesium 400mg daily, and CoQ10 300mg daily). If Tinnitus is a part of neuropathy, then I tend to recommend Alpha-Lipoic Acid 600mg-1200mg daily, B12 1000mcg, and Magnesium 400mg as options to safely try. The data isn’t as clear on dosing, and there are reasons to both think these are helpful as well as to be skeptical that I don’t have time to discuss thoroughly. Lastly, a very long list of generally safe supplements have had variable results for tinnitus not associated with another condition. They include about 3 cups of coffee worth of Caffeine (morning of course), melatonin 3-10mg (nightly of course), 5 HTP or Tryptophan, Goldenseal, Acai, Goji, Ginkgo, Zinc, Maritime pine, and if you’re not on prescribed medicines at all, St John’s Wort (seems to interact with every medicine).
Muscle aches and pains are another common condition where people request supplements. Again, it often depends on the patient’s condition as to which I recommend. Especially in muscle aches, I think a metabolic panel, thyroid and parathyroid studies, and a neurological exam are warranted before just throwing supplements at it. Thyroid related muscle aches are not going to get better with Magnesium, and low magnesium muscle aches need it. After a basic rule out for other causes, I think most people benefit from aggressive hydration with electrolytes (LMNT style, see hydration) far better than any mixture of herbs. In addition to that, and different types of physical therapies, if muscle fatigue is the prominent syndrome, I tend to support the use of supplements that have been studied in the “mitochondrial cocktail”. Again, the data makes this a “might be effective, most likely safe” sort of medical recommendation. Alpha Lipoic Acid 600-1200mg daily, Vitamin E (lower than 500 IU), Vitamin C (super high doses pretty safe, Liposomal Vitamin C tends to be best absorbed), CoQ10 300mg daily is a pretty safe regimen that has at least SOME supportive data. Turmeric supplements are often recommended for inflammation, though there is concern that some sources may under-estimate the dose and excessive dosing of turmeric can lead to liver trouble. Also, to be effective, Turmeric must be activated with piperine (usually found in black pepper) and consumed with foods higher in fat content. I recommend standardized and researched turmeric compounds such as Curcumin C3 complex instead of general turmeric supplements.
OK. Now I must again put the disclaimer that Supplements are less well-controlled than prescription meds, very rarely have good effectiveness data, and in some cases can be toxic. I cannot count the number of neuropathy patients I have had who had toxic levels of B6 because their three multivitamins all had too much. Also, in general, tablets are a much less useful way of getting vitamins and minerals than food or beverages due to absorption and other issues. Some Supplements require other things to properly work (like thiamine needing magnesium to work). Some supplements can interfere with the absorption of other supplements, like too much Zinc leading to Copper deficiency.
Other supplements being studied for effects in Long-Covid or ME/CFS - The best data shows 500mg of Liposomal vitamin C and 1.66 G of L-Arginine per day seemed to help fatigue and shortness of breath. N-acetylcysteine 600mg daily was found to have some benefit when prescribed with guanfacine (an adrenaline modulating agent used in ADHD). CoQ 10 with ALA (amounts used above) did improve fatigue in some patients. Omega 3 fatty acids had a small benefit with depression, myalgia, and cough with no good placebo control.
Choosing a supplement
When choosing a supplement, there are a few things to look for that can help make sure you are getting the supplement you want in the labeled dose in an effective form. First, look for supplements that are trademarked. They will have the familiar Ⓡ behind the active ingredient. A good example of this applies to Turmeric. Curcumin C3 Complex® is a specific, patented blend of curcuminoids that has been used in double-blinded studies showing evidence that turmeric can help reduce inflammation and oxidative stress. Next, look for a seal/certification from a third-party entity such as US Pharmacopeia (USP), NSF International, or ConsumerLab. These seals indicate the product has undergone independent testing for quality and purity and contains what the label says it does, is free from harmful contaminants, and has been manufactured according to quality standards. Then, look at the active ingredient listed on the supplement. Is it the right dose? Is the supplement the right form for what you are trying to treat? Some supplements have specific forms that can work differently or vary in effectiveness. Magnesium is a great example of this. Many amino acid supplements come in L and D forms. The L form is typically the bioactive form you are looking for. Also look for fillers such as titanium powder or talcum powder - these may be found in cheaper supplement versions and it is better to look for supplements without “extras” that may not be needed.
And most importantly, I may not be the best person to ask about this. I know it is funny to put that at the bottom of the article, but I must admit (actually one of my favorite pastimes) to the inadequacy of Western medicine on this issue. A well-trained nutritionist may be the best person to ask from a Western medical perspective, but if they seem overly confident I would avoid them. They have the same limited Western science I do. The truth is that despite my love of PubMed searches for peer-reviewed journals (where all my data comes from), Western science is too regimented to consider subtle patient differences and they often only follow subjects for a few months. If a supplement helps one group of muscle pain patients and hurts a different group, the data will be all over the place depending on how the patients were recruited.
All is not lost, however, because different disciplines of medicine like Traditional Chinese Medicine have had over 2000 years to refine their science in herbal medicine. You can’t just go to somebody who took a 6 month speed course in acupuncture though. You have to find someone who has actually trained in TCM. They’ll do things like look at your tongue every time, feel your 18 wrist pulses (yes there are 3 sites, 3 depths, and 2 arms). They’ll give you a diagnosis like wind in the liver, and they’ll use metaphors that I cannot begin to understand despite the multiple books I’ve read on the topic. However, they have a deep history rooted in curiosity, trial, and continued improvement. They are much more attentive to monitoring and self criticism, seeing a thousand flavors of body type, gender, habits, and personality as ways to predict effectiveness. While I know a handful of supplements that are most likely safe, and may be effective, I must give way to higher authorities on the matter.
However, if supplements aren’t breaking through, I’ve got some GREAT drugs you can try that I know are safer and more effective than natural supplements like arsenic!
Individual Supplements/Compounds
Turmeric - Curcumin C3 Complex® and Theracurmin® are both highly effective and researched, trademarked compounds. They contain the active curcuminoids found in turmeric. Turmeric known for anti-inflammatory effect, which can help pain and hypersensitivity. Piperine increases bioavailability and effectiveness, but may not be inherently needed for these 2 trademarked compounds
Magnesium - 400mg of glycinate good starting point, but dose depends on response and type of magnesium
Glycinate - best for sleep, well-absorbed, gentlest on the GI tract
Magnesium Citrate - best for GI health, indigestion, mild constipation, less likely than Magnesium oxide to cause loose stools, also can help with leg cramps
Magnesium Oxide - cheap, less bioavailable, effective for moving the bowels
Magnesium Sulfate - good for external use (Epsom salt baths, topical magnesium) for muscle aches and cramping
Magnesium Chloride - easily absorbed topically, good for those with absorption issues, shown to help with pain in fibromyalgia
CoQ 10 - 300mg daily - antioxidant, supportive of mitochondrial energy - Look for Ubiquinol, this is a reduced form of CoQ10 and is more bioavailable than other forms, often what has been used in research regarding the effectiveness and usefulness of CoQ10; fat soluble, take with fats
Melatonin - 3-10mg daily - Doses may range from 0.5mg-20mg - Most effective when used daily, taken at sundown or bedtime (same time every night) to help with sleep
Eggshell Membrane - 300-500mg daily - Contains collagen nutrients and hyaluronic acid, supports bone and cartilage, may help with hydration, joint viscosity, elasticity; Look for trademarked compounds such as Ovomet and NEM
L-Theanine - 200-400mg daily - Helps stress/anxiety, sleep, and ADHD - Takes about 30 minutes to take effect, generally it helps with relaxation while maintaining wakefulness and focus
Liposomal Vitamin C - 500-1000mg daily - supports elastin and collagen, aids in histamine breakdown; can help bruising, immune support, and pain. Liposomal is the best absorbed version of Vitamin C
PEA (Palmitoylethanolamide) - 600mg BID for 3 weeks, then once daily for 4 weeks was studied for pain and inflammation. PEA is produced by the body to regulate pain and inflammation. It can modulate mast cells and help decrease pain hypersensitivity due to its anti-inflammatory effect
Quercetin - 500-1000mg daily - antioxidant and anti-inflammatory effects that might help reduce swelling, kill cancer cells, control blood sugar, and help prevent heart disease. May help with allergies by controlling histamine release from Mast Cells
Vitamin B12 - check B12 levels with blood work before supplementing. Low levels are associated with fatigue and cognitive complaints; if blood testing reveals levels >500, supplementation unlikely to help significantly
Vitamin D - Check levels prior to starting supplementation. Patients with levels <30 are likely to benefit from supplementation
MTHF-5 - Supplementation useful in patients with a mutation of the MTHFR gene. Useful for cognitive, mood, and general fatigue symptoms
Alpha Lipoic Acid - 600-1200mg daily; antioxidant that helps with energy metabolism and nerve pain; recommended for neuropathy, muscle aches (part of the mitochondrial cocktail)
L-Arginine - 1.66g per day in combination with 500mg Liposomal Vit C may help fatigue and shortness of breath
N-acetylcysteine - 600mg daily in combination with the ADHD medication Guanfacine may help fatigue
Mitochondrial cocktail: Alpha Lipoic Acid 600-1200mg daily, Vitamin E (lower than 500 IU), Vitamin C (super high doses pretty safe, Liposomal Vitamin C, at least 500mg daily tends to be best absorbed), CoQ10 300mg
