I have written quite a bit recently about the methylation cycle and its relation to nutrient balance. At Wise Traditions this November in Anaheim, one of my three talks will expand these ideas to include targeting methylation nutrition to individual needs based on genetics and health status. Here, I’d like to chip away at one small piece of the puzzle that I have not written about yet: why benefits from SAMe supplementation should cause one to look not only at the most commonly discussed methylation nutrients (e.g., B12, folate, choline, betaine, methionine) and genetic polymorphisms (e.g., MTHFR) but also at issues that are more commonly neglected when discussing methylation: magnesium and the metabolic rate.
In my previous posts and articles, I have simplified the methylation cycle in order to make the nutritional topics I was discussing easier to understand. One thing I have left out (e.g., here and here) is that before methionine can be used for methylation it must be activated to S-adenosyl-methione, which is sold as a supplement and in the supplement market generally abbreviated as SAMe.
The Mayo Clinic has conveniently collected information on the doses of SAMe that treat a variety of conditions, as well as ratings of the evidence that SAMe is beneficial for a variety of conditions. SAMe is a very expensive supplement, so it makes sense to dig a little deeper and see why the supplementation may be necessary.
Joel Brind, a Baruch College professor of human biology and endocrinology whose research on methionine/glycine balance I have cited in the past has been blogging on Matt Stone’s site and recently addressed this topic himself. In the most recent post, he suggested that some people who have genetic difficulties recycling methionine from homocysteine may need small doses of methionine to hold them over between meals, which they can get from a small methionine-rich snack.
Indeed, any problems recycling methionine from homocysteine should be fully investigated because if these are the real problems then an expensive supplement like SAMe is a waste of money. These conditions would tend to be associated with elevated levels of homocysteine and they could include deficiencies of B12 or folate, especially in the context of a diet that is not rich in choline or betaine, or genetic polymorphisms in the pathways of these nutrients. They could also result from a deficient intake of methionine itself, which would be most likely on a very low-protein vegan diet or a diet that is outright deficient in protein, and this may not (necessarily) be associated with any elevation of homocysteine.
There is another possibility, however, that is strongly suggested by the biochemistry: some people may not be efficiently activating methionine to SAMe. In order for this activation to take place, the enzyme methionine adenosyltransferase (MAT, also known as S-adenosyl methionine synthetase) breaks apart ATP to harvest from it a molecule of adenosine and then activates methionine by sticking adenosine onto it.
People who have severe genetic deficiencies of the MAT enzyme are unable to use methionine, even when adequately present, for the methylation process. This is because that methionine is never activated to SAMe. Thus, they are deficient in methylation, they have little risk of depleting glycine by consuming excess methionine if the problem isn’t fixed (though they still may have inadequate glycine for other purposes, such as detoxification and synthesizing collagen), and since they never use up the methionine to make homocysteine, their methionine becomes elevated rather than their homocysteine, and their homocysteine is actually low.
The biochemistry suggests that people with a normally functioning MAT gene could have two other reasons for poor activation of methionine: poor magnesium status, or a low metabolic rate. Since ATP is the source of the activating molecule, the reaction is, quite clearly, ATP-dependent. Since ATP is always utilized as a chelate with magnesium, the reaction is also magnesium-dependent. The presence of a magnesium deficiency, a low metabolic rate, or both conditions together, could prevent methionine from being activated.
It is important to realize, however, that a low metabolic rate or a magnesium deficiency will compromise thousands of bodily processes, and that either condition would be likely to coexist with multiple nutrient deficiencies. Thus, such a person will not necessarily replicate the presentation of someone with a genetic deficiency of the MAT enzyme. They will not, for example, necessarily have low homocysteine. If the recycling of homocysteine is also being compromised, then homocysteine could be normal or elevated even while methionine is failing to be utilized properly and is thereby generating homocysteine at a much lower rate.
In my opinion, if someone benefits from SAMe supplementation or suffers from any of the conditions for which SAMe supplementation has shown to be beneficial, and it can be ruled out that simply ensuring adequacy of dietary methionine and relevant B vitamins would fix the problem, magnesium status and metabolic rate should be evaluated.
Magnesium concentrations in serum, plasma, red blood cells, and urine can be useful in assessing magnesium status, but probably should not be used to rule out the possibility that magnesium supplementation could be helpful. In addition to supplementation, proper stress and sleep management as well as eating a wide variety of unrefined plant foods can help with magnesium status.
Ensuring a normal basal body temperature is, in my current opinion, probably the most cost-effective and helpful way to address the metabolic rate. However, addressing why the metabolism may have slowed may be more complicated. Managing stress and sleep, ensuring adequacy of most nutrients, and eating enough total food and carbohydrate are probably the key factors to consider.
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Several years ago I tried to use SAM-e because it was recommended to me for help with anxiety. This supplement was not that expensive at the time so I tried it for about 1 week and discovered it made my anxiety even worse, and also created a new problem – panic attacks. What type of methionine rich snacks are you referring to in your article?
I have had homocystein checked (only once about 6 years ago) because my doctor’s office will not test for it, they do the useless cholesterol testing. I do not have a family history of cholesterol type issues, so to me that’s a useless, non-indicative “test”. But homocystein is different. Mine was perfectly normal at that time. I use magnesium in various ways (oils, soaking in epsom salt baths, Mag Asporotate capsules, etc) so I think my mag levels are adequate, but my metabolism is extremely slow. I’ve done the basal body temp testing many times and it shows no issues should be present. My sleep cycle is bad – I’m awake more than I’m asleep ever since menopause.
We eat pasture raised meats, very little chicken however because we don’t have access, but we do consume pastured chicken eggs often. We drink good water, have only occasional alcohol, take few supplements, and we try to eat “organic” as much as possible, although the status of organic foods is up for debate. I try to grow a garden but for the past three years we’ve had such different weather patterns in this area and such a short growing season we’ve had little to no garden fresh homegrown veggies, so we must depend on farmers markets (also questionable) and food co-ops. Still, we try.
Do you have any suggestions as to why my metabolism might be slow or my sleep cycle always being interrupted?
Yes, you may have “sleep-disordered breathing” due to some issue that affects your airway by making it narrow or occlude when your body attempts the deeper phases of sleep. Read Sleep Interrupted and about the Buteko method and basically tape your mouth to sleep. I use nose strips to open my nose, and blue painters tape (allows use of lip balm & to fold an edge to lift away if you need to speak or sneeze). You will not snore, and your oxygenation Wil improve along with your depth of sleep + this recovery and metabolism. Of course you should be eating a grain-free, ketogenic diet and following good sleep hygiene protocols. Get your thyroid situation lab tests and if necessary use natural or compounded thyroid supplements. Also address menopausal estrogen depletion with a functional medicine MD. I like Divigel by rx.
An additional hidden problem interrupting sleep and damaging health is non-wall-alarm-activating levels of Carbon Monoxide found in many homes. Your gas stove, water heater, heater and gas fireplace are almost certainly putting out CO. Read about the problems by searching for Albert Donnay. Then shut off all those sources of gasses and stick with electrics.
I have solved my cold intolerance and low Matabolism . 3 changes have done. 1.- TS Supplementation from Dr. Wilson, 2.- HGH Glandular Stimuli via Peptides, Sermorelin and CJC No Dac ( females use with Dac..). And the inclusion of Nat’l Dissecated Thyroid extract Armour plus my 20 years levothyroxine supp. ( Actually I have dimiinished my levo dose due to higher metabolic rate…? ) LMB ( mexico) forgive my spelling. From the three factors I guess the most important is the first one, it took about 2 months to be felt but the change in body temp. was very noticeable…
What is TS?
Such a treat indeed to read an article that is able to blend complicated and vital science and nutritional issues together in understandable language that gives us useable and beneficial health information. SAMe does indeed carry a top shelf price, and it is pleasing to know that we have viable alternatives.
Even though genetics is probably the most complex of sciences, we have learned more in the past few years that all that was ever known by humans. Genetic sciences are still in their infancy and there is little we can do now to intervene with genetic disorders, However, that is about to change in extraordinary and profound ways in the very near future (More on that later).
Regarding relevant supplements and whole food suggestions, please consult your primary care provider before eating or drinking anything.
For those of us who are cost conscious, research dug up some interesting facts:
Magnesium: 400mg $.06 ea.
D3 2000IU $.02 ea.
K – K2 complex $.09 ea.
A (as beta carotene from marine algae Salina) $.10 (every other day)
A and E Red Palm Oil 1 tsp. $.10
(Sources: Vitacost, Cosco, Sprouts, WalMart)
For those of us who prefer AU-NATUREL :
With a juicer/extractor, make two or more gallons (for less than $25) of super concentrated whole juice mix containing mixed berries, asparagus, brussel sprouts, broccoli, beets with tops, carrots, red cabbage, black grapes, kale, spinach, mushrooms, red bell peppers, tomatoes, and anything else you like.
This concoction provides copious amounts of fiber, micronutrients and carbohydrates, all in the best whole foods form possible, and it forms the basis of a novel and extraordinary diet spawned from deep research that is a hybrid mix of the best parts of the paleo and Mediterranean diets blended with the dietary recommendations from the Weston A. Price Foundation’s Wist traditions…
(More on this later)
Hi Chris,
excellent information. Thank you. The most practical and cheapest way to check for basal body temperature that I know of, is to check basal temperature before getting up in the morning with a thermometer. Do you feel that this is a reliable way to determine basal body temperature? I am familiar with Broda Barnes’ work but wonder if you have any more information about this?
Another approach to all of this is to consider that certain types of foods will lead to imbalances and thus problems with methylation etc, instead of saying that people are different. Yes, people are genetically different, and the bodies of people that are sick, aged etc may be less efficient in doing various processes, but people also eat differently.
Today the average American probably eat around 150 gm muscle meat and 50 gm cheese. He eats less egg yolks, drinks less milk, and eats less organ meats than in the past.
For example while 75 gm misc organ meats + 75 gm muscle meats plus 500 ml whole milk can provide 4 mg vitamin B5 and 400 mg choline, 150 gm muscle meats plus 50 gm cheese may provide just a little over 1 mg b5 and 100 mg choline.
In other words vitamin B5 is a nutrient we should investigate more. It is related to all these things; metabolism, fatty liver, high LDL cholesterol etc. High doses (pantethine) seems to be able to help fix these things, but smaller amounts found in natural foods along with other co-nutrients (like choline) may be more effective, and there will be synergy effects.
While human milk is low in folate, b12, methionine etc, it is relatively higher than other vitamins vs the RDA for choline and b5 (as well as for vitamin C and vitamin A).
I think there´s a case to be made for eating leafy greens, to consider it a special type of needed food, not only a «vegetable» along with all the others. It´s not only because of nutrients like folate and K1, but likely many others, especially perhaps chlorophyll – I think chlorophyll, also related to the detox process, can be considered kind of a semi essential nutrient, that will greatly assist when other processes fails.
In nature carnivores obtain relatively little magnesium, and often 10-30 times more calcium than magnesium. The human body also has around 30 times more calcium than magnesium. In milk it´s like 10 times more. It is clearly a nutrient related mostly to carbohydrate metabolism, and lots of white sugar should cause a deficiency, and to a lesser extent refined grains, while fruits, tubers, potatoes etc will provide all the needed magnesium (and other nutrients). Whole grains would be rich in magnesium, but not in a very good form, and will miss many other nutrients needed for carbohydrate metabolism, such as potassium. The combination of refined grains and large quantities of vegetables, as in the case of Japanese and Italian cuisine, seems to be fine.
Anyone living on pizza and soft drinks would obviously get all these problems. Supplementing magnesium will just fix the tip of the iceberg for them.
It is common to observe that milk drinkers are slim, while heavy cheese eaters are often fat.
The role of fruit and natural sugar and potassium in metabolism should also be investigated. It´s been shown in some of the paleo diet trials that just replacing whole grains with fruits effectively boost metabolism and leads to weight loss.
But yeah, eating enough calories and calories is the most essential of all. But in conjunction with the required nutrients in a reasonable balance with each other.
Thank you Chris for sharing such an interesting article. What type of health practitioner could help me diagnose and treat the nutrient imbalances related to the methylation cycle? My GP doesn’t seem knowledgeable about such issues, even though the lab has flagged many problems with my blood work related to folate, B12 etc.
Kind regards,
Terri
Am curious why my trying SAMe caused chest pain (mild but concerning), so called maker of it and no response. Looked in my nutrition books and it seems SAMe can make homocysteine, so I tried a B’s vitamin and pain left. Must be others who it causes problems and figured why.