This page is about both dietary supplements and herbal medicines. What they have in common, is that they are molecules that are used by living organisms in their metabolism. Pharmaceuticals, on the other hand, are not part of any living organism's metabolism. Read more.
Websites you can look at to review the worth of the individual supplements:
www.examine.com - this one used to have links to the research, from which they drew their conclusions, but now you have to pay to view them.
www.selfhacked.com now www.selfdecode.com
www.labdoor.com - although their rankings are completely bogus, and thus probably paid for, you can look at the data for an individual supplement and compare it to the others.
www.lifeextension.com - although a conflict of interest since they sell supplements.
key (supplements not fully labelled):
A helps with acne
D helps with depression
J helps with joint issues
N is a nootropic
a small pinch of saffron and, dermal dhea and pregnenolone, coffee, yohimbine, theanine
First meal: everything else except:
Bedtime: magnesium, melatonin, gaba
Below are notes that went into forming this stack.
To my supplement stack above, I switched from Vitamin Code Multi to Now Adam Softgels. I take half servings of multivitamins. I also added Amla and Eleuthero. Also I was adding maca to my smoothies. This has resulted in intestinal distress. So, I'm going to backtrack.
Eleuthero seems to be pretty gentle. So I'll keep taking the 1.7 grams (4 capsules). I'll cut out the Amla, the Adam Softgel, and the maca, and see if my intestines get a break. They have been doing so well until recently. Update: No more upset tummy.
I've been reading that maca should be cooked, or it causes stomach distress. I dumped the rest of my maca powder into water, boiled it for 10 minutes, and made maca ice cubes. I'm going to stay away from these for a while.
Amla is loaded with vitamin C, and I was taking 2 grams of it. Maybe I was taking too much vitamin C? “A tolerable upper limit (TUL) of 2,000 mg per day has been established” Side effect is stomach distress. Yet I read people having a half teaspoon of amla powder per serving, and then twice a day, adding up to about 4.2 grams daily. Maybe some of the other herbs I take have vitamin C as well?
I didn't like the vitamin mega doses of Adam softgels, but they are cheaper. Wondering about mega-dosing, I came across a site that explains that the DV is simply the amount needed to avoid disease, not the optimal amount needed per day. However, that explanation is not exact. The RDA is set at two SDs above the EAR, where the EAR would be the average amount needed for half of the population to be healthy. 1 Another site used the term Optimum Daily Intake, which is also bogus.
It's not like I'm not eating. I get nutrients elsewhere. I don't want a multivitamin to go beyond the minimum. Excess can also do harm.
Wikipedia's coverage of systematic reviews shows no benefit to taking multivitamins. I differ because modern produce is nutrient deficient, due to GMO and lesser quality soil. Also, I may not always eat a balanced diet.
I don't like that Vitamin Code Multi got bought out by some huge corporation, so I was looking elsewhere. I was looking at VitaminIQ or Naturelo, but the reviews I found on them, suspiciously where being pumped up by another website designed to trick google into improving the SEO. This bogus website. I could tell it was a bogus website, because, besides not having anything besides lawyer-speak pages, and unrelated blog entries, it borrowed images directly from the servers where I found the multivitamin reviews (information I have thanks to my using ublock origin). So I can't find any independent reviews, aside from perhaps labdoor and consumerlab. Neither of these have reviewed Naturelo or VitaminIQ, so I guess I am going to stick with Vitamin Code for now.
May add Bromelain, Amla, Eleuthero
May take all supplements with coffee in morning, with ghee and inositol (“bulletproof” style), along with ~4g glucomannan which slows digestion and increases absorption
Now Supplements sells Gaba that includes B6, because B6 is a cofactor in forming Gaba in the brain. However, I don't think I need to take B6 with Gaba, unless I am deficient in B6. “Eighty to ninety percent of vitamin B6 in the body is found in muscles and estimated body stores amount to about 170 mg with a half-life of 25-33 days.” source. More detailed info on plasma b6 levels.
Quote from Lifespan.io, Josh Conway: “As a general rule, as researchers discover more about aging, they often find that it is a panoply of processes, even within individual hallmarks of aging. For example, there is currently no broad senolytic treatment that destroys all senescent cells; instead, different senescent cell types require different senolytics. It should be absolutely no surprise, then, that genomic instability is turning out to be a broad term that refers to multiple types of genetic damage, each of which has its own symptoms and potential therapies.”
May add Astragalus Membranaceus1.
Considering taking the following during a flu: https://examine.com/supplements/andrographis-paniculata. Also zinc and elderberry lozenges or syrup. Also considered https://examine.com/supplements/pelargonium-sidoides, except that the “vast majority” of studies were funded by a company that sells a patented extract.
Absorption comparison of different curcumin formulations:
Turmeric is not easily absorbed on its own. Piperine, a component of black pepper, aids in its absorption. Absorption can be increased alternatively by other methods, such as complexing with phospholipids (such as the Meriva formulation). Turmeric standardized to 95% curcumins, is often just called Curcumin. Even if not absorbed, turmeric helps the digestive system.
“In his biography, Max Planck remarked: A new scientific truth does not triumph by convincing its opponents and making them see the light, but rather because its opponents eventually die, and a new generation grows up that is familiar with it. … I am optimistic (or naïve?) enough to hope that Max Planck was wrong. During his whole life, Francis Crick emphasized the importance of theories and models in guiding experimental work and helping to eliminate lines of research leading to dead ends (Morange, 2008).” (Heininger 2012)
So, it's important to think about what I'm trying to do here. I am trying to optimize nutrition, such that my body receives the right molecules at the right times, at the right concentrations and dosages.
The nutritional density of most industrial-agrarian food is lower than optimal, so I try to increase it by supplementing. I also try to decrease the energy density of the food by increasing the fiber content.
I still need to investigate the content of the entries 20191014 and 20191008
I've added yohimbine, that should be taken in the morning on an empty stomach. I was confused about dosages. Apparently, you can take a lot of it, but small dosages appear to be just as effective, and larger dosages can cause side effects. Similar to dosing melatonin, if just as a metaphor.
Update: Maybe the better option for this is intermittent fasting? See https://lifeapps.io/fasting/the-5-stages-of-intermittent-fasting
Update: Maybe the better option for this is niacin: https://www.lifespan.io/news/niacin-increases-nad-significantly-in-human-trial
Nicotinamide riboside is claimed to be a new form pyridine-nucleoside of vitamin B₃ that functions as a precursor to nicotinamide adenine dinucleotide or NAD+
COI: The study was funded by https://www.chromadex.com
Review of https://www.youtube.com/watch?v=kG2aQKghDBw
Oliver Medvedic March 1, 2019
1) Flavinoids found in fruits and vegetables, higher dosages, are found to clear out senescent cells with low toxicity
2) Intermittent fasting helps clear damage, not just senescent cells, but damage that accumulates such as shortened telomeres, or misfolded proteins, and reduction of inflammation caused by senescent cells
3) Fisetin is a flavinoid that is very effective at sweeping out senescent cells. Bioavailability (absorption?) is an issue.
4) You don't take Fisetin continuously. You mega-dose for a day or two to clear out senescent cells.
Fisetin is mentioned on an Examine.com page about myricetin. Myricetin is stated to have a higher antioxidant potency than quercetin and fisetin.
“Of the 10 flavonoids tested, fisetin was the most potent senolytic.” Yousefzadeha 2018
resveratrol, fisetin, luteolin, rutin, epigallocatechin gallate, curcumin, pirfenidone, myricetin, apigenin, catechin, and quercetin.
“At a lower dose (112 mg/kg), fisetin didn't significantly increase apoptosis or lead to liver toxicity. Intermittent dosing and use of a form of fisetin with increased bioavailability are likely to mitigate the risk of liver toxicity.” fightaging.org 2019
112mg/kg is about 8 grams for a 160lb person. Fisetin with increased bioavailability example:
However, I don't believe they are using a bioavailable version of fisetin in the phase 2 clinical trial:
The idea of taking a supplement intermittently, like once every six months, clears the way for the use of heavy anti-oxidant / bioflavinoid / phytonutrients that may hamper the signal for beneficial growth and repair, since they do not have to be taken continuously. Will need to research this and update the article on antioxidants.
Iodine and K2
Rosemary, Turmeric, Ginger, Holy Basil, Organic Green Tea,
Hu Zhang (Polygonum cuspidatum) (root and rhizome),
Chinese Goldthread (Coptis chinensis) (rhizome),
Barberry (Berberis vulgaris) (root bark),
Organic Oregano, Chinese Skullcap
PQQ – goes well with CoQ10
C60 – mitochondrial enhancer.
Trans-Resveratrol and Leucine. synergistic.
Possible sleep herbs/supplements:
Why are so many sleep herbs anti-androgen or estrogenic? Most of the research is on women, so maybe the effect is related to improved hormone regulation, rather than being anti-androgenic. Maybe the phytoestrogens compete with estrogen, not just promoting the pathway.1 So it's complicated. I was taking chamomile, valerian, and skullcap before bed, but have discontinued until I have a definite conclusion. Even ginkgo, green tea extract, and panax ginseng are implicated, but I will continue to take those for now, as I've been taking them forever. Example research: Plant Derived Anti-Androgens.
“The results of the present study led to the conclusion that the isoflavone dosage (40 mg) in the supplement, which is similar to the amounts consumed in many Eastern nations , had no effect on gonadotrophin or sex hormone levels or on semen quality. However, the studies in experimental animals suggest that exposure to phytoestrogens in the developmental period is not advisable . Moreover, the results of our study do not exclude the possibility that supplementation at a higher dose or over a more prolonged period would produce modifications in male reproductive health.” (Mitchel et al 2001)
“Exposure to endocrine disruptors (e.g. BPA or dioxins) during critical periods of reproductive development increases the incidence of reproductive disorders. Given the popularity of soy‐based formula, isoflavone supplements and soy‐derived products, a better understanding of the influence of phyto‐oestrogens on male development is needed. To date, there has been a lack of consistency in human and animal studies examining the effects of soy and phyto‐oestrogens on reproductive parameters. These discrepancies certainly reflect the variety of experimental designs, the differences between the specific endpoints measured but also inadequate descriptions or insufficient sample size to permit confidence in the observed results. In humans for example, it would be important to investigate adult male reproductive and endocrine functions of healthy full‐term infant fed soy‐based formula compared with breast‐fed or cow milk formula‐fed infants. These studies should investigate pubertal development and reproductive endpoints such as adult testicular function (testicular volume, spermiogram) and endocrine parameters (testosterone, DHT, oestradiol, LH, FSH, IGF1, INSL3, etc). The cohorts should be large enough to ensure statistical power to detect meaningful differences. Concerning animal studies, the choice of the animal model and nutritional differences in animal diets need to be considered carefully when designing experiment. It would be relevant to assess dose response relationships, mutigenerational studies and evaluation of both reproductive and post‐natal endpoints. Finally, most studies are designed to investigate the effects of a single endocrine disrupting chemical. Although straightforward in term of scientific design, this approach fails to appreciate the chemical soup that is more typical of the human or animal environment. Thus further investigation is needed to evaluate the consequences of simultaneous exposure to phyto‐oestrogens and other EDCs on fertility and testicular function.” (Cederoth et al 2010)
Basically, it's “we know nothing”, except that it does have effects. If you are an aging woman, my guess is that taking them is beneficial to make up for decreased hormone levels. If you are male, they should be avoided.
This meta-analysis found that “Whey protein alone or as a part of a multi-ingredient appears to maximize lean body mass or fat-free mass gain, as well as upper and lower body strength improvement… ” However, the study was funded in part by GlaxoSmithKline-Maxinutrition. Looking up info on this company, I found: “GlaxoSmithKline (GSK) and Maxinutrition Group Holdings Limited today announced they have entered into an agreement for GSK to acquire Maxinutrition, a UK company that manufactures protein-enhanced functional nutrition products, from Darwin Private Equity.” This is a very big conflict of interest (COI). Previous studies on COI, have shown that study results have a strong correlation with industry funding, and shouldn't be trusted.
Currently not taking Saffron, though I may take it again. Undecided.
I am waking up after 5 hours of sleep, usually due to bad dreams from events in the last few years. I see on this page that modified release melatonin clears after 5-7 hours. I am having success taking an additional 1mg of regular melatonin and going back to sleep for a full 8 hours. Melatonin without modified-release formulation clears in about 2-3 hours.
This 2009 study shows that time release melatonin improves sleep quality. Unfortunately, it was funded by a pharma company (shows “FORENAP pharma”, but if you download the full text, you will see Neurim Pharma, in Tel Aviv), thus the results are practically worthless. Another 2007 study from Neurim. I found several studies, dating from 1995 to 2010, with similar conclusions, and they were all funded by Neurim pharmaceuticals. Very suspicious to have several publications from different years from the same funding source. Another study on children with neurodevelopmental disabilities, but with one of the authors also having a pharma connection. I am disappointed that Examine.com didn't mention this detail, which leaves a lot of sleuthing work to be done in the future for results I have taken for granted. I still believe melatonin may be beneficial to supplement (due to hormonal decline in old age), but improvements in sleep quality or insomnia is not a proven benefit.
Due to getting a cold, I looked for a decongestant. No surprise, one of the main pharma decongestants, phenylephrine, doesn't work better than placebo. I found bromelaine: there isn't sufficient studies to be conclusive, but people seem to be happy with it on Amazon.
Standardized valerian is 0.8 to 1 % valerenic acid. I don't know the percentage of valerenic acid in the whole herb. The best I could find is from Botanicals.com. Botanicals.com says “The chief constituent of Valerian is a yellowish-green to brownish-yellow oil, which is present in the dried root to the extent of 0.5 to 2 per cent though an average yield rarely exceeds 0.8 per cent. This variation in quantity is partly explained by the influence of locality, a dry, stony soil, yielding a root richer in oil than one that is moist and fertile.”
Educated guess is that the standardized valerian extract is not much more potent than the root. Standardized in this case means a reliable dosage of what is thought to be the “active ingredients”. However, it is not always reliably known which constituents are the actives, and that is the reason I often prefer to take half extract and half herb (more comments regarding this in 20170717).
Extract to herb comparison from SigmaAldrich: “ Constituents: The purported active components of gotu kola, accounting for 1-8% of the constituents, include asiatic acid, madecassic acid, asiaticoside, asiaticoside A, and asiaticoside B. The leaves of Centella asiatica have also been reported to contain 170mg calcium, 30mg phosphorous, 3.1mg iron, 414mg potassium, 6.58mg beta-carotene, 0.15mg thiamine, 0.14mg riboflavin, 1.2mg niacin, and 4mg asorbic acid. “
Examine says: ” While there are currently no human studies on cognitive enhancement, rat studies have noted success with 200-300 mg per kilogram of the overall plant extract (since the saponins may not be the only active ingredient for cognition); this suggests a human dose of 32-48 mg/kg and thus:
2,100-3,300 mg for a 150lb person
2,900-4,400 mg for a 200lb person
3,600-5,500 mg for a 250lb person
The above dosages ranges are but estimates for cognitive enhancement. Currently, 500mg of centella asiatica twice daily has shown anxiety reducing effects in humans and 750mg of a 5% asiaticoside extract has enhanced mood state; while these doses are active on the cognition, it is not yet demonstrated if they are the dose needed to boost learning. “
Compare 5% asiaticoside extract to a herb constituents 1-8% of asiatic acid, madecassic acid, asiaticoside, asiaticoside A, and asiaticoside B.
Examine also notes that Bacopa has similar effects on the same metabolic pathways, and it is unknown if they can be used together or if one is more potent than the other. Since I am taking both, I don't need the full dose.
Examine.com: ” Bacoside A and B with A being up to 8% of the dry leaves by weight when fresh. Other Bacosides may be present in contents ranging from 1.43% (bacopaside-I) to 2.74% (bacopaside-II) “
” The standard dose for Bacopa monnieri is 300mg, assuming that the total bacoside content (the active compound) is 55% of the extract, by weight.
Bacopa monnieri can also be supplemented in a leaf or powder form. To achieve the ideal 10-20% of bacoside content requires a dose of 750-1,500mg of the leaf or powder. “
Supplements not to be taken together:
Iron and green tea: If you mix iron with green tea, black tea, or curcumin supplements, your body won’t absorb the mineral.
Looking into adding amla, valerian, lavender, gaba, theanine (in addition to green tea extract), black cumin and astragalus. I just noticed that amla is part of triphala. I noticed gaba is reduced in children with adhd.
Looking into zinc supplementation more closely, all the research points to a *deficiency* in zinc causing issues. Kurtis Frank at Examine writes: “One of the more common micronutrient deficiencies in athletes, vegetarians/vegans, and those who sweat a ton. Not really a common deficiency otherwise.” I have been supplementing 50mg, which is a bit high. I get some zinc also from the multi-vitamin, so I'm going to discontinue supplementing zinc. I had thought that zinc was an aromatase inhibitor, and even examine.com quotes that it is at high dosages, but I can't find any research to support this (examine.com does not have a supporting reference, and self-hacked has a reference that is completely incorrect… what?! red flag!). Too much zinc can be harmful 123.
I contacted examine.com telling them that they wrote: “In very high doses, zinc can act as an aromatase inhibitor and reduce estrogen levels.” I told them: “I can't find any proof of this. What research backs this claim? I can only find that a deficiency in zinc can cause lowered testosterone.” Wyatt at examine responded: “I can't find any either; that part could use some editing. For now, don't believe that zinc can reduce estrogen levels, only that it increases testosterone.”
Looking into natural aromatase inhibitors: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3074486. I hypothesize that aromatase inhibitors may be necessary because of the pollution of plastics into so much of our food and drink. Grape seed extract looks interesting, but research is not conclusive. 12
Articles on balancing the amount of methyl-donors consumed (including SAMe, choline, and betaine):
I'm not taking crazy amounts: SAMe 400mg, betaine 1000mg, alpha-gpc 600mg (Alpha-GPC is approximately 40% choline by weight)
Looking into: https://www.nutrahacker.com
Curcumin works better when taken with Boswellia:
Boswellia and Curcumin complement each other in covering all pathways to inflammation (see table 1): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4877453
Good article on safety of creatine:
I take a small pinch of saffron (approx 13 strands, and should be taken with starch for better absorption) and apply the hormones in the morning. I take the melatonin and magnesium at night. I also take 100mg of time release 5-htp at night, and hope to be tapering off of it, as long term use can deplete the other monoamines. I have been taking 5-htp morning and night, for 4.5 months, most of this period at a dose of 200mg twice a day (I was rather desperate, and overwhelmed by the volume of information), under the presumption that my seratonin has been low, though I haven't had any bloodwork to confirm it. At least I was taking a MAOI like rhodiola, although just once a day (what's the half life of these MAOI's?).
The rest of the supplements above I take with a meal: only the supplements I take at night are mostly on an empty stomach. As far as I can tell, all supplements in my stack are in two categories: a) take with food or b) take with or without food (based on reading bottle labels, and sources 1 2. Which makes sense because you get nutrients from food. Source 2 says to take “botanicals” on an empty stomach, but it doesn't match up with looking up instructions for botanicals individually.
Amino acid supplements 1, like carnitine 2 or the amino acid derivative nac 3 may compete with other amino acids (protein) for absorption, so it may be better to take them on an empty stomach unless it irritates your digestion. Although not well documented, the same could be said of SAMe 4, which is the amino acid methionine bound to an ATP molecule. I need more scientific proof that these should be taken separate from a meal to not reduce protein absorption by competition. Taking supplements in the morning may affect my intermittent fasting schedule, but one must choose the lesser of two weavils.
20180820: for a month, I took nac, carnitine, and SAMe separate in the morning, along with a chewable inulin fiber gummy. I stopped this because I was having a mucus discharge (either the pills or the gummies: the gummies were not agreeing with me previously so maybe it has nothing to do with the pills?). I think the mucus is a sign of intestinal irritation 12 Cessation returned me to normal. I may try again using glucomannan fiber pills instead of the inulin gummies, or maybe with a bit of ketogenic food to not break fat burning during my intermittent fasting. However, I'm content to take all my supplements together for a while. I do have more than one meal a day.
I am taking Zinc 50mg with food. ” Zinc’s intestinal uptake is hindered by other minerals, including calcium, magnesium, and iron, since they all use the same transporter. If the transporter’s uptake limit (800mg) is exceeding between these four minerals, absorption rates will fall. Taking less than 800mg of these four minerals at the same time is fine. ” source Let's see… two cups of milk has 600mg of calcium 1. I could worry about reducing the intake of other minerals by supplementing zinc 50mg, however, 50/800 is a small percentage. I could include it instead with the amino acids I have started taking in the morning. My arbitrary decision is to take with food to reduce chance I am already taking (with the amino acids in previous paragraph) of upsetting my stomach. That decision may change.
It takes quite a bit of water to down all these pills. However, it's best to NOT consume too much water with a meal. The best way I have found to take the pills, is to use a little bit of water to swallow the pills, then use some food to get the pills to go all the way to the stomach. I sometimes feel like they get stuck at the bottom of my throat, and that goes away with swallowing a bite or two of food.
I had concluded that dermal hormone application was the way to go (instead of oral), based on reviewing the literature. I haven't looked at my notes, but what I remember was that when taking hormones orally, the blood content of hormones was unnaturally elevated and dropped off quickly. Then I discovered time/sustained/extended/slow release tablets. I am considering using both, oral whenever dermal isn't convenient. So I started reading again. Dermal application of hormones bypasses the intestines and liver, so the hormones absorbed by the blood differ from oral delivery. Oral delivers metabolites of the hormones to the blood, including DHEA-S. This article says: “ DHEA-S is a different pro-hormone and has different benefits than DHEA. Medical research shows DHEA is converted into DHEA-S, but not the other way around. So, DHEA-S is not converted by the body into DHEA. ” If dermal application is superior, why is so much research done on oral administration? While nutrients naturally go through the digestive tract, delivery of hormones through the digestive system doesn't seem natural to me. Maybe the hormones are altered along the way to produce molecules that could cause side effects (agreeing with an opinion I found on the internet).
The following supplements seem to be related to each other by metabolic pathways, so I'm wondering if the same results can be had without taking all of them: S-adenosylmethionine, choline, creatine, d-serine, sarcosine, glycine.
“ Choline and its metabolites are needed for three main physiological purposes: structural integrity and signaling roles for cell membranes, cholinergic neurotransmission (acetylcholine synthesis), and a major source for methyl groups via its metabolite, trimethylglycine (betaine), which participates in the S-adenosylmethionine (SAMe) synthesis pathways. ” from wikipedia
“ Sarcosine is formed from dietary intake of choline and from the metabolism of methionine, and is rapidly degraded to glycine, which, in addition to its importance as a constituent of protein, plays a significant role in various physiological processes as a prime metabolic source of components of living cells such as glutathione, creatine, purines and serine. ” from wikipedia
“ Sarcosine is significantly more effective in treating Major Depression (substantially improved scores on the Hamilton Depression Rating Scale, Clinical Global Impression, and Global Assessment of Function) than Citalopram over a 6-week period. Sarcosine was well tolerated without significant side effects. ” from wikipedia
“ Sarcosine’s main mechanism involves inhibiting a transporter, called GlyT1, which takes up glycine and D-serine into cells. This increases the levels of glycine and D-serine in the body and increases their effects. ” from selfhacked.com
“ Oral supplementation of choline appears to be sufficient in increasing plasma betaine concentrations, and at least at the 1,000mg dosage it appears to be just as potent as betaine at increasing plasma betaine concentrations ” from examine.com
“ In addition to dietary sources, betaine can be produced through the irreversible oxidation of choline via choline dehydrogenase and betaine aldehyde dehydrogenase. ” from here
Multifarious Beneficial Effect of Nonessential Amino Acid, Glycine: A Review:
“ Glycine is most important and simple, nonessential amino acid in humans, animals, and many mammals. Generally, glycine is synthesized from choline, serine, hydroxyproline, and threonine through interorgan metabolism in which kidneys and liver are the primarily involved. Generally in common feeding conditions, glycine is not sufficiently synthesized in humans, animals, and birds. Glycine acts as precursor for several key metabolites of low molecular weight such as creatine, glutathione, haem, purines, and porphyrins. Glycine is very effective in improving the health and supports the growth and well-being of humans and animals. There are overwhelming reports supporting the role of supplementary glycine in prevention of many diseases and disorders including cancer. Dietary supplementation of proper dose of glycine is effectual in treating metabolic disorders in patients with cardiovascular diseases, several inflammatory diseases, obesity, cancers, and diabetes. Glycine also has the property to enhance the quality of sleep and neurological functions. In this review we will focus on the metabolism of glycine in humans and animals and the recent findings and advances about the beneficial effects and protection of glycine in different disease states. “
” The biochemical studies … proved that glycine is synthesized from threonine (through threonine dehydrogenase pathway), choline (via formation of sarcosine), and serine (through serine hydroxymethyltransferase [SHMT]) “
” Methyl groups are generated in the mammalian tissues during degradation of choline to glycine. Generally in adult rats around 40–45% of the choline uptake is converted to glycine and this value can sometimes increases up to 70% when the choline uptake is very low. By conversion of choline to betaine by betaine aldehyde dehydrogenase and choline dehydrogenase , the three methyl groups of choline are readily available for three different conversions: (1) sarcosine into glycine by sarcosine dehydrogenase enzyme, (2) by using betaine from betaine-homocysteine methyltransferase as methyl donor and converting homocysteine into methionine, and (3) in conversion of dimethylglycine into sarcosine by dimethylglycine dehydrogenase enzyme. Sarcosine dehydrogenase and dimethylglycine dehydrogenase are the largely present in pancreas, lungs, liver, kidneys, oviduct, and thymus and these two enzymes are mitochondrial flavoenzymes . Through transmethylation, glycine and sarcosine are interconvertible. Sarcosine dehydrogenase has very crucial role in glycine-sarcosine cycle, as it controls the ratio of S-adenosylhomocysteine to S-adenosylmethionine. The reactions involving the transfer of methyl group in cells are largely affected by S-adenosylhomocysteine to S-adenosylmethionine. If the content of choline in diet is very low, then glycine synthesis is quantitatively very low in mammals. ”
Here, here, and here, the positive effects from adequate intake of choline or betaine (tmg) are used almost interchangeably. Likewise at examine, they state “Serum betaine is increased to a similar degree with 1g betaine as it is with 1g of Choline supplementation, and the latter may have some centrally acting (brain related) benefits to working out while possibly being cheaper”. Wikipedia states: “Sarcosine is found naturally as an intermediate in the metabolism of choline to glycine”. I'm going to conclude, that I only need to take choline, and not any of its metabolites. However, I'm confused by wikipedia stating: “Dimethylglycine is a derivative of the amino acid glycine with the structural formula (CH3)2NCH2COOH. It can be found in beans and liver. It can be formed from trimethylglycine upon the loss of one of its methyl groups. It is also a byproduct of the metabolism of choline”. Seems glycine can also convert to sarcosine and dimethylglycine, maybe as some form of homeostasis that balances the individual quantities, in which case I wouldn't have to worry about it. I don't want to make that assumption, though.
Consider that the NMDA agonists include sarcosine, glycine, and serine
“ 2,400mg choline bitartrate (1g choline) daily for twelve weeks in postmenopausal women (may have higher requirements for dietary choline) has been noted to not only increase plasma choline at weeks six and twelve (from a medium value of 7.33µM to 11.1-11.7µM) but also plasma TMG (from a median value of 30.7µM to 54.6-65µM, or 77-111%) and dimethylglycine (from 3.53µM to 3.92-4.63µM) under steady state conditions. “
” Serum betaine is increased to a similar degree with 1g betaine as it is with 1g of Choline supplementation, and the latter may have some centrally acting (brain related) benefits to working out while possibly being cheaper ” Which is why I added taking TMG (betaine) to my stack, in addition to a low dose of Alpha GPC (choline).
Google images, ripped from various studies:
Sometimes I take coconut oil with my morning stack, although I often wait until my first meal to take supplements, as I'm not a fan of eating oil. It's an option though, because if I'm fasting I can only take water soluble supplements. Most supplements are fat soluble or should be taken with food, for better absorption. So if I want the start the day super powered, and not break my fast, I must have coconut oil or some bites of fatty food.
If I down coconut oil with the supplements in the morning, I can do a 20 hour psuedo-fast instead of the usual goal of 16 (see intermittent fasting). The coconut oil gives me some steady energy until the first meal of the day. Taking in only fat content in the morning will keep me in keto. 28 grams, or two tablespoons of oil is sufficient for absorption of carotenoids in this experiment, and I will assume it is so for all fat soluble supplements.
20180414 I just wait for my first meal instead of using coconut oil.
A helps with acne
D helps with depression
J helps with joint issues
N is a nootropic
E is that I have taken the time to look up if it can be taken on an empty stomach, and it is true
two tablespoons of coconut oil (for improved absorption of the other supplements)
DJN fish oil ( equivalent of 1g of EPA: see section on depression) *
vitamin code multi
DJN curcumin plus regular turmeric powder
green tea extract
J glucosamine sulfate (20180414 substituting green lipped mussell for glucosamine+chondroitin)
J methylsulfonylmethane (MSM)
J bamboo extract
DJN s-adenosyl methinione (SAMe)
D ashwagandha (+5HT2 and -5HT1A serotonergic)
D rhodiola (serotonergic)
(see details about these hormones here: http://raypeat.com/articles/articles/three-hormones.shtml, and note the steroidogenesis here: https://en.wikipedia.org/wiki/Pregnenolone#/media/File:Steroidogenesis.svg)
20170916 Adding to my stack:
N alpha gpc (choline)
DN bacopa (serotonergic)
DN gotu kola
NE theanine (taking green tea extract already)
A niacin (500mg, short term experiment, no longer taking)
20171127 Adding to my stack:
20180223 Adding to my stack:
D 5-htp, time release (serotonergic) discontinued on 20180713, as it was temporary measure (see notes on 20170621)
D saffron (-5HT2C serotonergic) (all 9 studies regarding effects on depression come from Iran, which is the leading producer of saffron)
20180406 Adding to my stack:
D holy basil
Regarding Kava, Examine says: “300mg of this extract daily (in three divided doses of 100mg) appears to be reliable and effective for the treatment of anxiety… Doses of up to 800mg of the WS1490 extract have been tolerated for short periods of time.” The extract referred to is WS1490, which is 70% kavalactones (210mg daily). However Kava Guru states: “Depending on how it’s prepared, a bilo (coconut shell bowl) of kava can contain anywhere from 150 to 500 mg of kavalactones, and indigenous islanders often consume several bilos in a kava drinking session . In other words, although the Kava Committee has issued an advisory upper limit of 300 mg of kavalactones per day, many Pacific Islanders consume far higher doses of this wondrous plant daily without ill effects” Although Kava Guru sells Kava, I think what they say is true, despite the conflict of interest. The stuff I take is 30%, and I take 750mg at once (225mg) in the beginning of my day. I also take another 750mg before bed. Taking it this way, I have felt more relaxed, but I'm also forgetting to take it sometimes, as I haven't been at home. Regarding how long kava lasts in the system: “pharmacodynamic peaks at 1-2 hours and eight hours, suggesting active metabolites” 1 . So the initial effect comes in at 2 hours, but there are active metabolites thereafter that last much longer 2. I am hoping the concentration of kavain does not come close to 300uM (micromoles/liter), as this can cause some damage in the lacunosum moleculare layer of the hippocampus. I have no idea how to translate dosage to uM in the brain.
Before bedtime, I take 3g biphasic time release melatonin, 150mg theanine, 750mg (30%) kava, 100mg magnesium, and make my room as dark as possible, cover my window so no morning light will enter, and put on earplugs.
I think I was growing tolerance to rhodiola. When I stopped taking everything above (pre-20170916), while traveling, I was a mess for a few days. I am not interested in doing another reset until I am over someone I've lost. Rhodiola is known as an adaptogen, so maybe I'll just keep taking it for the other benefits it provides, even if I grow tolerance. ← deleted as I no longer think rhodiola tolerance is a thing
I take a morning stack, focused on getting me through the depression I've had since february. I take it on an empty stomach because I still practice daily intermittent fasting. I'm hoping the fish oil is a sufficient fat source to improve the absorption of the herbs. I take the fiber as a carrier so there is some bulk to slow things down in the digestive system, but this idea is pure speculation (a DIY time release dose of the rather large amount of ashwagandha and rhodiola I'm taking).
The following deleted because of additional research regarding fiber:
EDIT on 20170823: There is also speculation fiber can prohibit full absorption of nutrients, and should be taken separately from supplements: “Although not enough evidence exists to suggest this is a huge concern, it may be prudent to separate psyllium supplementation from mineral supplementation” examine.com. In addition to the research examine found on the topic, I found 1 and 2 experiments that show absorption is minimally affected by fiber, even at 25 grams per day. I think it is good to simulate what happens when people eat plant foods normally high in nutrients. My hypothesis is that the natural process optimizes the following two:
1) the amount of supplement absorbed
2) steady absorption (instead of an absorption spike in the timeline) The research mentioned in the previous paragraph was done on fiber *added* to a normal diet, whereas the assortment of pills here does not constitute a meal. If a meal is one of three a day, that would have approximately 8 grams of fiber, comprising a percentage of that meal. I'm going to guess-timate and take 0.6 grams of fiber (1 pill) of glucomannan with the morning stack that is taken on an empty stomach. By weight it's a small amount. The volume of glucomannan, however, is higher than other fibers (absorbs more water than other fibers), but I'm not sure by what factor. Another consideration: “ Eating a lot of fiber won’t block your body’s ability to absorb every vitamin and mineral – only a select few. Those nutrients include iron, zinc, magnesium, calcium and phosphorus. Because fiber-rich foods tend to be such valuable sources of vitamins and minerals, however, the National Institutes of Health states that absorbing too few minerals from high-fiber foods is rarely an issue. ” source
This is the morning stack:
fish oil ( equivalent of 1g of EPA: see section on depression)
s-adenosyl methinione (SAMe)
There are plenty of other supplements that aid with depression, but these are morning specific because I think they may have a more immediate effect. Specifically ashwagandha and rhodiola, being mind altering nootropics. I believe they are often paired together in ayurveda, based on repetitive google searches. Both are adaptogens, especially ashwagandha. Rhodiola is a stimulant, while ashwagandha gives a feeling of well-being (including reducing cortisol levels). SAMe is not mind altering directly, but helps with depression and it would be good to take more than once a day.
To this I plan to add other nootropics I discussed in 20170724. I want to add the raw egg and MCT oil to the coffee, but I am trying to figure out the effect on intermittent fasting. If it still keeps me in ketosis, then does it still have all the benefits of fasting, or are other benefits interrupted by the intake of calories? One of the biggest benefits for me with intermittent fasting, is improved digestion. Later on in the day with a big meal, I take:
vitamin code multi
glucomannan (as needed)
curcumin plus regular turmeric powder
s-adenosyl methinione (SAMe)
Before bedtime, I take a 1g or 3g time release melatonin, make my room as dark as possible, cover my window so no morning light will enter, and put on earplugs.
Went to a biohacker meetup where I was told a good beginner stack for getting mental work done is the combination of piracetam, choline, coffee, and theanine. Throwing in a raw egg into the hot coffee is yummy (added choline). These are to be taken for a mission/objective, and are not to be taken daily like adaptogens. I never even have caffeine, but I intend to try nootropics to combat ADD and PTSD (and the possible result of depression: a shrunken hippocampus).
In addition to turmeric, I will be taking curcumin with an absorption enhancer such as piperine, because of what examine says on the matter: “If using curcumin for intestinal purposes, then absorption from the intestines into the blood is not necessarily required. Due to this, one can simply use turmeric at the dose of 2-4g daily or take curcumin supplementation without any of the aforementioned enhancements”. Most studies are geared to standardized extracts, but sites such as this one say that curcumin free turmeric has benefits. I wonder what an ayurvedic doctor would say. Now foods covers the herb vs extract dilemma well, while consumerlab is more inclined towards extracts. Consumerlab covers the food vs supplement dilemma well.
I have been choosing herbs instead of herb extracts, defaulting to the thought that natural sources are better. I could see how the industry would push for extracts. But it's not just industry: scientific research needs standardized extracts to get consistent results. Product purity is a concern (extracts tend to be more pure), and I am influenced by what products labdoor and consumerlab tests (mostly the extracts). Despite the push for extracts, the decision should be taken on a case by case basis.
What I may do, is take both the extract and the herb. For example, there are turmeric/curcumin mixes available as a single pill, or just taking two low dose pills would also work. There are also whole herb extracts (standardized to include all the molecules that may play a synergistic role), as mentioned in one of the previous links. Mega-dosing the herb (or whole herb extract) to get the desired amount of concentrated-active-ingredient from a single extract pill may either be just inconvenient, or it may be beneficial.
I found some evidence that in the past, consumerlab had found many turmeric supplements to not pass in their testing. Since I signed up recently, to their subscription, I saw that all turmeric products in their list were pretty fine. So I sent them this letter:
A few years ago 33% of turmeric supplement brands failed testing, and now I can't seem to find these products reviewed by consumerlab. I found a site that mentioned 3 brands that failed testing. Yet these brands are no longer reviewed by consumerlab. Why not?
Advanced Physician Formulas Curcumin (FAILED TESTING),
Eclectic Institute Turmeric (FAILED TESTING),
Progressive Labs Curcumin BCM-95 (FAILED TESTING),
I got the following response:
Products are chosen for review based on their popularity with our subscribers. Product popularity is determined by an annual survey as well as subscriber write-ins and subject to change from review to review.
Mark Anderson, Ph.D.
To which I responded:
Why would your subscribers choose to take supplements that don't pass inspection? You will end up with reports that don't have any bad products. Seems more useful to know there are bad products out there. It would give a false sense of security for one to see that there are hardly any bad products, and make it more likely that people will trust less expensive options, or whatever the local store has at the moment. Had you considered this outcome?
In the past, consumerlab has been sued by companies who's products did not pass their inspection. They have also taken heat from Council for Responsible Nutrition, which is a “trade association and lobbying group representing the dietary supplement and functional food industry”. Perhaps this or some other reason is their true motive. Or perhaps there is sincerity: it may cost a lot of money to test supplements. However, they could include previous year's testing, since old information is still relevant in knowing the reputation of a company. I do notice that Consumerlab's testing for Ashwagandha currently includes a lot of products that fail testing. I doubt consumerlab subscribers will continue to take products that fail testing.
My knees are giving out, and the left achilles is complaining. It's time to take a look at supplements for joint health. I am not going to put together a report tonight. I've been reading examine.com, consumerlab, labdoor, research articles, and misc sites. My initial direction for supplement choices was given to me by Willie, who is a retired professional ballerina and is now an instructor. She recommended biosil™, msm, fish oil, turmeric, and diatomaceous earth. There isn't conclusive research for some of these, as too much research focus is driven by industry profit. I ordered the list below, every last one a swanson brand (update: I may not be doing that in the future, given a couple of their supplements had toxins: https://labdoor.com/review?q=swanson). I later found luckyvitamin to have relatively good prices on brands I can find in labdoor or consumerlab.
s-adenosyl methinione (SAMe)
bamboo extract (silica)
diatomaceous earth (silicon dioxide) (temporary use)
Bamboo extract provides silica → Si, instead of the more expensive orthosilicic acid like biosil, which I think is a bit gimicky, based on absorption research compared to some foods (and beer). MMST is more bioavailable than biosil, but not yet available as a supplement. I'm wary of taking diatomaceous earth forever, as even food grade may contain some unwanted elements like aluminum. I could only find one study about DE relating to cholesterol, and it wasn't placebo controlled. It could be just for the added silicon (Si). Some of the rest of my supplements have specific joint health benefits, like turmeric:
vitamin code multi
now ultra omega 3 fish oil (best quality/cost ratio at the time)
doctor's best high absorption magnesium (most people are deficient)
now glucomannan (taken as needed with low fiber foods)
life flo dermal dhea
life flo dermal pregnenolone
I notice that life flo dhea contains:
zinc, saw palmetto, MSM, panax ginseng, chamomile extract, & grape seed extract
unfortunately also contains phenoxyethanol + caprylyl glycol, potassium sorbate, stearic acid, cetyl alcohol, and stearyl alcohol
I notice that life flo pregnenolone contains:
sodium hyaluronate (skin hydration), MSM, sunflower seed oil, shea butter, allantoin, & evening primrose oil
unfortunately also contains potassium sorbate, stearic acid, glyceryl stearate, phenoxyethanol + caprylyl glycol
I see I am already getting some MSM from life flo dermals. How much I don't know, as it isn't listed. So for joint health, compared to Willie's original list, I'm only adding silicon (simplified concept derived from biosil and diatomaceous earth). It would be nice to reduce the number of supplements. Some self experimentation is due (I would much rather rely on research, as my perceptions can be unreliable). Also reading articles like Review of Anti-Inflammatory Herbal Medicines, which has a chart that categorizes herbs into the type of inflammation they counteract.
Very poor note taking. Lots of reading. The conclusion is that everything is good for you… truly frustrating. Some top down knowledge would be nice.
Hormones also affect neurotransmitters. I am supplementing both DHEA and Pregnenolone. I thought maybe supplementing hormones would also cover the decline in neurotransmitters with age. The uncertainty factor remains high:
DHEA in one or two rat studies shows to reduce the activity of monoamine oxidase, which would leave more monoamines like serotonin, dopamine (and derivatives), and histamine, working in the brain. https://www.ncbi.nlm.nih.gov/pubmed/18307051. Pregnenolone, which has progesterone as a derivative, is shown to also decrease the activity of monoamine oxidase (at least in vitro https://www.ncbi.nlm.nih.gov/pubmed/8420316). Some sites like selfhacked and neuroendoimmune are claiming that progesterone increases MAO activity, based on this study: https://www.ncbi.nlm.nih.gov/pubmed/6835476, though I don't see a very strong correlation since this very study says: “without prior estrogen administration, progesterone did not affect MAO activity”.
The following guy draws a lot of educated guesses, in this case regarding the effects of higher and lower monoamine oxidase: https://selfhacked.com/2014/12/07/about-mao-a-and-what-to-do-if-you-have-the-warrior-gene/
The reason I use dermal as opposed to oral: "Bioavailability and metabolism of oral and percutaneous dehydroepiandrosterone in postmenopausal women"
DHEA and Pregnenolone also raise IGF-1 indirectly.
I'm leaving behind taking tryptophan, or 5-htp, on a daily basis, since I would have to also take l-dopa, and l-tyrosone, and sulfur amino acids in order to balance everything. Actually, I'm not sure if that's everything going through the blood brain barrier. Potential consequences of long term usage of 5-htp here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3415362. Also http://raypeat.com/articles/aging/tryptophan-serotonin-aging.shtml.
I am taking a both rhodiola and ashwagandha. Rhodiola reduces monoamine oxidase activity, and ashwagandha is an adaptogen that goes well with rhodiola.
Adaptogens galore! I don't know which to take. Examine.com stack guides are for specific purposes, but I'm looking for overall health supplements you take on a maintenance schedule. Assuming you would do such a thing. Supplements that would encourage a better homeostasis. Along the lines of anti-aging supplements. There are tons of articles and science that prove a dozen herbs are great for you, but would you take all of them??? Maybe on a molecular level, the herbs can be put into groups of derived benefit, where the derived benefits number is much lesser than the number of herbs that contribute to them. I can't find a site that does this. Likely this knowledge has yet to be integrated.
The other reason not to take too much tryptophan, an amino acid that gets converted to 5-htp, then serotonin, then melotonin, is that it can have severe side effects. Too many sites don't talk about this, as the internet seems to be pro-selling of all products. There are reasons why I think I may be low in serotonin. I've read you crave sweets and starchy carbs when you are low on serotonin. Also you don't sleep as long without a good supply of melotonin. Also, the U.S. water supply gets flouridated, which over time calcifies the pineal gland, which is responsible for tryptophan → 5-htp → serotonin → melotinin in the brain. “Serotonin does not cross the blood-brain barrier, so serotonin outside of the brain (in the gut, platelets, heart, and liver) stays separate from serotonin in the brain.”
Because hormones and neurotransmitters decline with age, I will be taking DHEA and pregnenolone.
I don't have a reliable aromatase inhibitor, to protect from stress imbalance and artificial environmental estrogens. The “DHEA for men” product includes grape seed extract, and I am going to go with that for lack of a better alternative, since I prefer to avoid pharma.
I found this record about Life Flo: https://www.casewatch.org/fdawarning/prod/2005/lifeflo.shtml.
Consumerlab won't let me check their tests without paying. I chose this brand because it's at Swanson Vitamins, and the only transdermal they have.
I chose tryptophan rather than 5-htp, because I want to provide something closer to a food substance:
“ Supplementation of 5-HTP has been shown to be more effective than tryptophan supplementation alone. This additional benefit of 5-HTP supplementation arises because 5-HTP bypasses the cell's L-tryptophan's own self-regulation on the IDO enzyme, in which it upregulates the activity of IDO (discussed in next section) to maintain body homeostasis of tryptophan and it bypasses the tryptophan hydroxylase enzyme, which is the rate limiting step in serotonin biosynthesis. ”
Even then, by taking too much tryptophan, I can develop tolerance:
“ The activity of tryptophan hydroxylase can also be further downregulated in cases of Magnesium or vitamin B6 deficiency, stress, or excessive tryptophan levels. “
Which is annoying because I would rather treat the cause rather than the symptom of decreased serotonin and melatonin with age.
Also starting to take gymnema sylvestre (meshashringi) for reducing the effects of sugar in my diet. I think a ton of other comparable plants could work also. Maybe there's a better, or rather, more studied choice. Seems like it's all about eating more plants. I don't feel optimistic about changing my diet, as living by myself I don't feel a lot of joy in preparing anything, and I just eat whatever is easiest. Also, using supplements appeals to me, as it is so much more quantifiable. Perhaps in time I'll start substituting vegetables for the individual supplements I take, but still have the supplement available as backup if I am short on time to make that happen.
I have been taking:
Vitamin Code Raw Multivitamin for men
magnesium (just started taking this, as my mom suggested it recently)
If I mention brand names, it's because I'd like you to tell me if you recommend a different one and why. I am not affiliated with Vitamin Code, or Life Flo.
The market is generally unregulated. In an investigation by the New York Attorney General's office, “found that several popular store-brand supplements at four major retailers — GNC, Target, Walgreens and Walmart — contained contaminants not listed among the labeled ingredients. Just 21 percent of them actually had the DNA of the plant species they purported to be vending.” source: pbs.org
Raw, whole food multivitamin
Fish Oil, or Krill Oil?
Best overview article: https://authoritynutrition.com/fiber-can-help-you-lose-weight/
Viscosity rather than quantity of dietary fibre predicts cholesterol-lowering effect in healthy individuals
” The degree of viscosity appears to be inversely related to glycemic response, with the more viscous dietary fibers producing greater effects. These fibers form viscous solutions when mixed with the gastrointestinal (GI)5 tract contents, slowing gastric emptying and thickening small intestinal contents. This may reduce contact between food and digestive enzymes and interfere with diffusion of nutrients to absorptive surfaces, thus slowing the rate at which glucose molecules become available for absorption at the small-intestinal brush border ” jn.nutrition.org
The following two, HPMC and MC, are not digested by bacteria in the gut, and therefore do not produce gas. I have been taking MC for about a decade. It works well. I am going to try some others, because I understand that you want fermentable fibers, to keep up the beneficial gut bacteria.
- HV-HPMC (hypromellose):
- Methylcellulose A4M:
the nominal viscosity of METHOCEL A4M is 4000 cPs measured as a 2% aqueous solution at 20C
I am going to take the following three. You can find them in 100% pure ground form.
“ 33% of Turmeric and Curcumin Supplements Selected for Testing Fail Quality Review ” https://www.consumerlab.com/reviews/turmeric-curcumin-supplements-spice-review/turmeric
I make my own using empty capsules, with tumeric from the food coop.
ConsumerLab appears to have conflicts of interest:
https://en.wikipedia.org/wiki/Talk:ConsumerLab.com/Archive_1 “I think it is important that the page make note of the following about ConsumerLab.com: 1) ConsumerLabs.com is a for-profit business and has nothing to do with Consumers Union, the non-profit publisher of Consumer Reports. 2) The company charges fees to manufacturers that affects the placement of products on the website. 3) The company is not a laboratory and does not perform laboratory tests. The company does not reveal who performs the tests. 4) The ConsumerLabs.com website lists a mailing address, 333 Mamaroneck Avenue White Plains, NY 10605, at which there is no building owned or rented in that name.”
PubMed Dietary Supplement Subset https://ods.od.nih.gov/Research/PubMed_Dietary_Supplement_Subset.aspx