Dear Mark: Amino Acid Supplements, Preventing an Infection, and Knee Pain in a Lunging Athlete

Dear Mark Amino Acid Supplements FinalFor today’s edition of Dear Mark, I’m answering three questions. First, are the amino acid supplements sarcosine, D-serine, and D-cycloserine worth taking? What do they do and who can they help? Next, what should you do to prevent an infection? Besides the regular stuff like vitamin C and vitamin D, is there anything else to take to mitigate the damage and prevent pathogenic incursions? And finally, I field a question from a fencer and martial artist who’s feeling the beginning twinges of knee pain. He leads a lunge-heavy life—it’s an inescapable part of his training—and I offer a few suggestions for limiting the damage.

Let’s go:

Dear Mark,

You have talked about branched chain amino acids before.
I was wondering how safe you believe the other Amino Acid supplements are?
In particular, Sarcosine, D-Serine, and D-Cycloserine?

Thank you


These aren’t the BCAAs you’re used to taking to enhance performance in the gym, fat loss, and body composition.

Sarcosine, D-serine, and D-cycloserine increase signaling at the NMDA receptor, a glutamate receptor that plays a huge role in depression, schizophrenia, addiction, anxiety and other mental disorders. Sarcosine is a glycine transporter-1 inhibitor; it reduces the amount of glycine taken up by cells, increases serum glycine levels, and makes more glycine available for binding with the NDMA receptor. D-serine is an NMDA co-agonist; it makes the NMDA receptor bind more effectively to other agonists. D-cycloserine is a partial NMDA co-agonist that also acts as an antibiotic against tuberculosis.

What are they good for?

They’ve all been studied in schizophrenia. In both long-term stable schizophrenia patients and patients suffering from acute episodes, sarcosine reduced the PANSS (positive and negative symptom score). D-serine improved symptoms, just not as effectively as sarcosine. Adding it to an antipsychotic regimen helped reduce symptoms, too. D-cycloserine is also effective against symptoms of schizophrenia when added to typical meds.

They may help against certain types of depression. Some types of depression are characterized by over-expression of NMDA receptors, while others are caused by low NMDA activity. As they enhance NMDA activity, sarcosine and D-serine may help with the latter type.

D-cycloserine shows promise in treating anxiety disorders, mostly as an enhancer of existing treatments. When you take it shortly before the exposure, cycloserine makes exposure therapy better at extinguishing anxiety and fear in a number of disorders including snake phobia, OCD, social anxiety, panic disorder, and acrophobia (no word on arachnophobia). It may also help older autistic kids and teens with their social skills.

As the NMDA receptor is a popular and viable target for cognitive enhancement, and enhancement of NMDA receptor function is a “core strategy” in combatting age-related cognitive decline, these amino acids may have potential as nootropics. Do they work?

It’s all very preliminary. In one study, D-serine improved working memory, sustained attention, verbal fluency, and reaction times. One group of researchers suggest D-serine may be “the key” to synaptic plasticity, which is required for learning something new or the formation of memories. Sarcosine should work pretty well for this, too, as it increases D-serine levels.

However, sarcosine is also elevated in patients with prostate cancer. It’s even found in the prostate tumor itself. Its relationship to prostate cancer isn’t strong enough to warrant using sarcosine as an early biomarker for detection of prostate cancer, but it may act as a co-carcinogen once the cancer has been established. This is extremely speculative, mind you.

So while these are probably “safe,” they’re mostly used for very specific treatments, often under medical supervision, and probably don’t have as much application to the general public. If you have any of the conditions listed above, mention these amino acids to your doctor and show some research.


As our family’s go to health Guru I have a question for you that I wasn’t able to find an answer to on your site already. I have a feeling I already know at least part of the answer from reading daily but here it is….

My wife and I have three children. My girls are 10 and 5 and my son is 9 months. Just the other day, my younger daughter and my son came down with the dreaded 24hour-ish stomach bug. Now my wife, older daughter and I feel like the poor victims on The Walking Dead” who have been bitten but not killed and are just waiting for the sickness to ensue. So my question is, outside of doubling down on Probiotics, Vitamins D and C and increasing water consumption, on top of a quality primal 90/10-ish diet, are there any other measures you would recommend to try and avoid coming down with the stomach bug ourselves?

Thanks for all that you do! You have been an incredible resource for our family over the last 4+ years.


There are a couple things you can try in addition to probiotics, vitamin D, and vitamin C, which are all good things to try:

Zinc: Taken at the onset of an infection, it can reduce the duration. Taken with vitamin C, it’s even more effective. Taken regularly, it can reduce the incidence of infections in people with zinc deficiency. Shoot for at least 45 mg of elemental zinc.

Garlic: Take an entire head of garlic, smash each clove, and let them sit for ten minutes. Drop into simmering broth for 3-4 minutes, until some but not all of the pungency has dissipated. Drink broth, eat garlic. This is a lot of garlic, but it seriously works wonders.

As far as probiotics go, make sure you’re taking one with L. plantarum. It’s the strain with the most efficacy against infections.

Bear in mind that most of the above research is on upper respiratory tract infections like cold and flu. The stomach flu, or gastroenteritis, can have a ton of different causes so it’s difficult to make specific recommendations. Hope it helps and good luck!

Hi Mark,

I’m a regular fencer and martial artist who’s passionate about the sports they love, I practice lunging and techniques almost every day but I’m hitting 30 in the next couple of years and I’m starting to get a few niggling pains in my knees I’m hoping to see a physiotherapist about soon.

All of this got me a bit scared because I’ve always hoped to keep primally healthy and practicing well into old age.

What advice do you have for diet exercise and lifestyle choices for keeping the knees healthy in the long term for those of us who regularly give them a pounding?


I don’t know enough about fencing or martial arts to offer specific modifications to your skill training, but I do have some general advice.


Check out MobilityWOD. Focus on the lower body MOBs (mobility workout of the day). Anything to do with hips, hip flexors, hamstrings, glutes, calves, ankles, feet, quads. Learn to love/hate the couch stretch.

Stretch your calves (often tight in lunging athletes, since lunges let you get away with tight calves whereas squats do not). These work well.

Switch to rear lunges when training. Obviously, when competing you’re going to be doing all sorts of forward lunges, but you don’t need to hammer that movement during training. Rear lunges will strengthen the same movement patterns in a controlled fashion.

Do some stability lunges. Get in a lunge position and hold it. Really stretch those hip flexors out. Get comfortable there.

Foam roll/lacrosse ball your legs. Get in there. Some say they don’t work, but I think they do.

Make the lunge a hip hinge, rather than forcing an upright posture. Hinging at the hip during a lunge with a little forward lean of the torso actually places more emphasis on the glutes and less on the knee, contrary to popular belief.


Get some collagen in your diet. Eat more gelatin-rich meats. Make/drink bone broth. Learn to cook oxtails, shanks, feet, hocks, and other collagenous animal parts. Try my collagen chocolate bars, which are delicious and get you most of the gelatin you need in a day. The human body requires at least 10 grams of glycine per day for basic metabolic processes, so we’re looking at an average daily deficit of 7 grams that we need to make up for through diet. With gelatin running about 33% glycine, aim for 21-25 grams of gelatin a day. Maybe even more, since you’re experiencing joint pain and glycine requirements go up in joint disorders.

Get your omega-3s. If you’re not eating fatty fish on a regular basis, that’s a no-brainer. Fish fat is anti-inflammatory, and although human evidence is mixed, the general consensus is that it improves joint pain. Besides, we know that omega-3s are important for other reasons, so why not try?

Eat turmeric or take curcumin. Curcuminoids from turmeric have shown efficacy against osteoarthritis (in addition to inflammatory disorders in general). A blend of turmeric extract, hydrolyzed collagen, and green tea extract looks like it might work pretty well.

Good luck!

Thanks for reading, everyone. Take care and be sure to help out with your input down below!

About the Author

Mark Sisson is the founder of Mark’s Daily Apple, godfather to the Primal food and lifestyle movement, and the New York Times bestselling author of The Keto Reset Diet. His latest book is Keto for Life, where he discusses how he combines the keto diet with a Primal lifestyle for optimal health and longevity. Mark is the author of numerous other books as well, including The Primal Blueprint, which was credited with turbocharging the growth of the primal/paleo movement back in 2009. After spending three decades researching and educating folks on why food is the key component to achieving and maintaining optimal wellness, Mark launched Primal Kitchen, a real-food company that creates Primal/paleo, keto, and Whole30-friendly kitchen staples.

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27 thoughts on “Dear Mark: Amino Acid Supplements, Preventing an Infection, and Knee Pain in a Lunging Athlete”

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  1. In regards to the knee pain, I am certainly not a fencer or martial artist…just a very active 49 year old who had some knee injuries running track in high school. I can tell you that I feel great consuming collagen on a daily basis. I never have any joint pain. I follow a pretty clean primal/paleo diet. Oh, and the turmeric is a good suggestion too. I don’t take a curcumin supplement (although I have heard that can be helpful) but I use turmeric regularly.

    1. I concur. But I would also put good money on the fencer just reaching the genetic limitations of his body. Martial arts and fencing everyday may always lead to more pain in the knees over time no matter what he/she does. I’m in great shape, but there are certain activities that are triggers for me and some I seem to have an unlimited capacity to endure. Overtime I’ve eliminated the trigger activities and gravitated towards the ones that don’t create problems. Everyone is like that. Maybe it’s time to drop one or the other or cut back on the number of training days.

      1. Seems that way. I’m attempting to gravitate more towards slower movements to train muscle memory rather than explosive movements every day, adding in some of those stretches plus a little more turmeric and gelatin to the diet. Cheers for the advice everyone!

        I really kneeded it.

  2. L-Glutamine is a reasonably safe amino acid supplement. Some people won’t react well to it but it has helped me in the past when I have had gastrointestinal problems(leaky gut). It’s also used for muscle repair and immune boosting. A nice leaky gut remedy is a big cup of bone broth with a scoop of L-Glutamine in it.

  3. Hello Mark, speaking of collagen…. I make a treat that include an assortment of freshly grounded nuts (250gr each), cacao powder and nibs, 100% bakers chocolate, 200gr grass fed butter, shredded coconut and coconut oil (1/2 cup) and tiny amount of black strap molasses (I love it). I spread the dense mix in a silicon tray (baking tray will work just as well) and stick it in the fridge to set. It’s naturally very rich so you can’t eat more the a small square or two but that’s the whole point.

    Based on your comment and your own bar (I can’t order it from overseas), I was wondering if I can incorporate a couple of tablespoons of “great lakes collagen hydrolysate” into the mixture as is – that is without melting it (I normally use it to make a hot drink hour or so before I go to bed), and able to absorbed it that way.


    1. 250 grams of butter is discretionary (good for those on Keto). Otherwise, 100 grams would suffice and just as tasty

  4. In regards to boosting immunity with kids in tow (mine are 8, 4 and 3 weeks), I will do the usual (Vit. C, D, zinc, probiotics, no sugar/grains) and for tummy bugs, I’ll take a shot or two of apple cider vinegar throughout the day diluted with water. Also, if I show any hint of it, I’ll take activated charcoal and it seems to help shorten the duration. I also take an extra dose of cod liver oil whenever anyone so much as sneezes at my house. I might just be immune to everything after being around small children germs so often, but I rarely get sick (knock on wood!!).I never like to say that too loudly, lest some crazy bug come through our house!

  5. Re: stomach flu:

    Wash your hands frequently and don’t touch your face.

    Simple, but most people forget.

  6. For fighting acute infections, both internally and topically, I would also add Silvercillin. It has good research behind it and I have used it with good effects.

  7. Regarding the amino acids: look into lithium orotate (lithium carbonate is usually used in huge amounts for bipolar; don’t let this frighten you), 5mg a day or so.

    It’s a nutrient many of us are missing, great for mental health in general, including schizophrenia (though I wouldn’t go as far as to say that it should replace any other treatment). It’s safe, cheap, and actually have a wide range of benefits. Including protecting the brain from other drugs.

  8. I sure wish your dark chocolate bars did NOT have almonds…my serious nut allergy won’t let me try them! Any plans for something with fewer allergy triggers? (Lots of people can’t so peanuts either…they’re not a problem for me, but as legumes I don’t eat them.)

    1. Me too on the nuts. Here in my advanced Middle Age (74) I’ve recently developed an allergy to all the nuts I love: Macadamia, Pecans, Walnuts, Almonds and Peanuts too and even pistachios. I mourn the loss. My mouth burns and I get the kind of migraine that causes auras and numbness when I eat them. Almost like a stroke. Has anyone else experienced adult onset allergies like this. I would love that collagen chocolate bar. I can’t do coconut either. Can’t remember if it has coconut.

      1. Yep, I’m 73, but I developed the allergy about 15 years ago, much to my dismay. I LOVE almonds and pecans…and black walnuts. But my lips and gums swell, I have trouble breathing, I sweat like crazy, my skin burns and my gut cramps…not worth it.

  9. Fencer — here’s my suggestion: work with a really good coach trainer, work basics and look for teeny, tiny little errors in your form that are gradually expressing themselves through this knee pain. You may have to take a step back and relearn/refine some basics, but it will serve you well in the end. Can’t hurt right?

  10. saccharomycin is also helpful for stomach bugs. It’s a Probiotics yeast.
    Specifically best after encounter with Ecoli and post antibiotic use.
    It can also be helpful with stomach bugs

  11. So while these are probably “safe,” they’re mostly used for very specific treatments, often under medical supervision, and probably don’t have as much application to the general public.

  12. Thanks for the knee insights Mark! Any modifications you’d make or additions for someone with a torn meniscus? Mine is manageable, but I’ll tweak it occasionally. I’d love to find a way to better strengthen that area. Thanks!

  13. We had great success with collagen and turmeric treating my husband’s knee pain after a nasty Crohn’s flare that landed him in the ER (plus a low carb, paleo diet!)
    Later on, adding ionic magnesium (liquid, not pill form) really had fantastic results. It increased ease of movement in joints and muscles for everyone I’ve recommended it to.
    Also, not sure if this is a direct result or just coincidence, but I started taking the ionic magnesium and collagen as well when my lifting plateaued a bit and saw a great increase in muscle tone and maximum lift shortly after.

  14. I wonder what methods might help with long standing shoulder pain that occurs with any upper body exercise.

  15. The MobilityWod voodoo wraps fixed my knees.
    I remember for a long time dreading to do lounges, with care and waiting for the pain in the knee that stays back …
    Not anymore, check out the videos of Kelly Starrett. on how to use the wraps.

  16. Fencer: Do you squat? If so, do you squat below parallel? It is very important to balance the forces acting on the knee, and lunges do not always have the knee travel below parallel at the bottom of the range of motion. This places stress on the knee joint which, over time and repetition, can lead to problems.

    1. Yep! Regular pistol squats though to attempt to even out the strength differences in the legs (is the suggestion here to barbell squat below parallel?). I also try to never lunge so far that the knee joint is beyond the ankle joint, it’s the classical advice from older fencing manuals.

  17. Edible clay is quite helpful for gastrointestinal bugs, and nicely primal too. But I’d make sure it’s labelled for internal use and get a copy of their lab analysis for lead content and other heavy metals.

  18. Does anyone have experience with glycine supplements for joint health? I’ve been supplementing with Great Lakes Gelatin but am wondering if it might be easier to just take isolated glycine supplements.

  19. I injured both knees at once back in 2010 and have had to deal with a lot of knee pain, including some real terrible aches that I imagine are comparable to arthritis, and what feels like some messed up scar tissue when I move the one knee in certain ways.
    Fish oil and salmon seemed to help a bit when I was on a diet high in those. I figured that the omega-3 increased production of synovial fluid. A quick skim over a couple sites tells me that omega-3 is good for the joints by reducing inflammation.
    Luckily as time goes on I’ve had less pain and at least in the past few months or so almost none and am optimistic about a good if slow recovery, though on occasion earlier this year I’ve had to cut some leg workouts short due to pain. I haven’t worked out much at all in the last year and a half, just tried to stay active, except while in custody, where I’ve spent a hell of a lot of time in my opinion, and do some calisthenics to try to be at least in somewhat decent shape. Possibly my most ambitious jail workout was the day I did 500 pushups (not perfect form but alright) and 1000 lunges. I worked my way up to that over months and on a good day when recovered I could hit those numbers, usually one or the other though. I like the sound of 1000.

    1. Edible clay is quite helpful for gastrointestinal bugs, and nicely primal too. But I’d make sure it’s labelled for internal use and get a copy of their lab analysis for lead content and other heavy metals.