62 replies to this topic

[Wry]

In the past I was taking over a dozen supplements, now I have reduced what I am taking down to these four:

 

•     Organic Powder (blend of grass juice, fruits and vegetables, sprouts, probiotics, and enzymes)
•     Reishi
•     Krill Oil
•     L-Carnosine

 

I feel fairly confident that supplementing these four items will improve my health and hopefully my life expectancy.

 

I am very skeptical about calorie restriction and antioxidants, or for that matter, taking supplements that have not been proven to be beneficial for humans in the long run. So essentially, I would like more information about what is known to be effective at increasing life expectancy in young healthy adults.

Edited by Wry, 14 July 2015 - 12:24 AM.

[Darryl]

Among compounds that extend life in rodents, only aspirin, metformin, and glucosamine have supporting evidence of reduced mortality in humans, though there have yet to be any long-term randomized trials with lifespan as an endpoint.

[JohnDoe999]

Wry

 

Why are you very skeptical about calorie restriction and antioxidants?

[Wry]

Among compounds that extend life in rodents, only aspirin, metformin, and glucosamine have supporting evidence of reduced mortality in humans, though there have yet to be any long-term randomized trials with lifespan as an endpoint.

 

I think I understand how those drugs can improve one's health and longevity, especially if one suffers from heart disease, type 2 diabeties, or other conditions where these drugs can be of benefit.

 

Wry
 
Why are you very skeptical about calorie restriction and antioxidants?

 

CR because it has not been shown to be successful in long lived mammals. Yet I do think that having a healthy diet with well proportional meals is very beneficial to one's health.

 

Antioxidants because of the potential for cancer. Oxidative damage can be important for preventing cancer development. Perhaps antioxidants would be safer if you took something else in addition that targeted cancer.

Edited by Wry, 14 July 2015 - 05:11 PM.

[Darryl]

Aspirin reduces overall mortality in those taking it to prevent first heart attacks, and reduces cancer incidence and mortality too. Diabetics taking metformin have 15% lower mortality than age matched non-diabetics. That's speaks very highly for its ability to reduce mortality. Glucosamine is taken for joint problems that don't have much association with mortality. These three compounds anti-aging mechanisms are by via the nutrient-sensing signalling which has been the central focus of experimental gerontology. Aspirin's metabolite salicylate is a direct allosteric AMPK activator. Metformin interferes with mitochondrial respiratory complex, making ATP production inefficient and indirectly activating AMPK. Glucosamine impairs glucose metabolism, again activating AMPK.

 

Alas none of the OPs supplements: hormetic Nrf2 activators (organic powder), immunomodulatory (sometimes excessively) β-glucans (reishi), omega-3 EPA (krill oil), carnosase bait (l-carnosine) have much effect on nutrient sensing pathways, and none have extended life in mammals. They seem more likely to offer benefits on stress resistance / reducing inflammation (though the β-glucans are Janus-faced) than affect more fundamental aging progression.

Edited by Darryl, 14 July 2015 - 05:45 PM.

[Wry]

Alas none of the OPs supplements: hormetic Nrf2 activators (organic powder), immunomodulatory (sometimes excessively) β-glucans (reishi), omega-3 EPA (krill oil), carnosase bait (l-carnosine) have much effect on nutrient sensing pathways, and none have extended life in mammals. They seem more likely to offer benefits on stress resistance / reducing inflammation (though the β-glucans are Janus-faced) than affect more fundamental aging progression.

 

Two studies on mice with l-carnosine:
http://www.ncbi.nlm....pubmed/10951107

 

Carnosine attenuates the development of senile features when used as a supplement to a standard diet of senescence accelerated mice (SAM). Its effect is apparent on physical and behavioral parameters and on average life span. Carnosine has a similar effect on mice of the control strain, but this is less pronounced due to the non-accelerated character of their senescence processes.

http://www.ncbi.nlm....pubmed/10841274

 

The naturally occurring dipeptide carnosine (beta-alanyl-L-histidine) has been found to exert an anti-senescence effect when used as a dietary supplement. Carnosine clearly improved the external appearance of experimental animals and provided beneficial physiological effects, thus maintaining the animals in better condition than control animals receiving no carnosine or a mixture of beta-alanine and L-histidine.

 

In cultured cells:
http://www.ncbi.nlm....pubmed/10951108

 

Carnosine is an endogenous free-radical scavenger. The latest research has indicated that apart from the function of protecting cells from oxidation-induced stress damage, carnosine appears to be able to extend the lifespan of cultured cells, rejuvenate senescent cells, inhibit the toxic effects of amyloid peptide (A beta), malondialdehyde, and hypochlorite to cells, inhibit glycosylation of proteins and protein-DNA and protein-protein cross-linking, and maintain cellular homeostasis. Also, carnosine seems to delay the impairment of eyesight with aging, effectively preventing and treating senile cataract and other age-related diseases. Therefore, carnosine may be applied to human being as a drug against aging.

 

Mushrooms like trametes, shiitake, reishi, cordyceps, maitake have been shown to offer great benefit. Such as fighting off cancer (such as prostate cancer), preventing auto immune disease, bolstering and regulating immunity, improving gut bacteria. These mushrooms contain and increase antioxidants, protect the liver, prevent diabetes and brain related diseases, and much more. Although I'm certain that there is potential for side-effects as well, such as liver damage. For that reason I wouldn't recommend taking them continuously or at high dosage.

Reishi has been shown to extend life in mice:

 

Ganoderma lucidum (Reishi) has long been used as a medicinal herb for immune enhancement and cancer prevention and adjuvant therapy. We previously reported that ReishiMax (RM), a Reishi extract enriched in Reishi polysaccharides and triterpenes, enhanced proliferations of macrophages, B, T and NK lymphocytes, increased serum IgA, IgG, IgM & secretion of IL2 and Interferon, decreased IL5 secretion, and inhibited cancer malignancy (FASEB J 2007, 21:A1100; 2008, 22:1136.2). In this study, we examined the effect of RM in lifespan extension in mice. Male and female ICR mice (12 months of age) were randomized to receive either mouse chaw alone or prior mixed with RM at a dose of 175, 350 or 700 mg/kg. Calorie intake was adjusted twice a week to match the levels for the male or female controls. RM treatment (88 wks so far) showed: (1) no significant differences in body weight and calorie intake among the groups; (2) compared to controls, lifespan was extended 30–66 days at 50% survival, 46–110 days at 20% survival and 61 to >148 days at 10% survival (the study is ongoing). Kaplan-Meier Survivor analysis showed significantly extended lifespan with RM and reduced death risks, with the best survivor curve observed in mice receiving RM supplementation at 175 mg/kg (equivalent to the human dose) (p=0.023). Our data thus far indicates that ReishiMax extends the lifespan of normal aging mice.

 

Other than the benefits krill oil shares with fish oil, it offers in addition astaxanthin (a powerful antioxidant). There's much benefit to be had from fish / krill oil.

Fish / fish oil being shown to extend lifespan of humans:
http://aje.oxfordjou...aje.kwt326.full

 

The study team kept tabs on more than 70,000 people for 5 years, monitoring their diet and supplement habits, as well as their death rates from all causes and from various diseases. Compared to those who ate little or no fish and did not take omega-3 (or fish oil) supplements, people who ate fish roughly once a week or who popped a daily omega-3 pill enjoyed an 18% drop in their mortality risk. The same group also lowered their risk of cancer death by 23%. - www.prevention.com

 

As for the organic powder, there is also much benefit to be had, so much so that I can hardly even begin to go into it. Two great benefits are that it alkalizes a person's body and that it supplies essential nutrients.

 

I would supply more references, but I'm afraid that I do not have enough time.
 

One more supplement that I have added to my short list is 1,000 IU of vitamin D3 in olive oil.

Edited by Wry, 14 July 2015 - 08:20 PM.

[JohnDoe999]

"Antioxidants because of the potential for cancer. Oxidative damage can be important for preventing cancer development. Perhaps antioxidants would be safer if you took something else in addition that targeted cancer"

 

IMO antioxidants are still considered very useful for prevention of various health issues, and thus for prolonging life (since the likelihood of dying of these health issue are lowered). There are however some considerations:

 

1) Vitamin C IV in high doses for cancer functions as a pro oxidant (but this is although useful)

2) You should not take some antioxidants when there is ongoing cancer in your body 

3) Some antioxidants, when taken in isolation, have been shown to increase the risk of negative health issues under some circumstances (f.ex beta carotene)

 

However, as far as my interpretation goes, research still has not shown that antioxidants are not beneficial for health, as long as two criteria are fulfilled:

 

1) You are healthy to begin with

2) You supplement with a wide range of antioxidants, not antioxidants in isolation. I.e. that you - as a minimum - adhere to the "antioxidant network", proposed by Dr. Lester Packer, and adds other antioxidants on top of this as well

 

 

Please correct me if I am wrong

 

 

[Kalliste]

Inefficient antioxidants are problematic. But efficient antioxidants like MitoQ, SkQ1 and C60 show a lot of tumorprevention promise. MitoQ can inhibit 100 % metastasis activation by blocking superoxide overloading of the electron transport chain. C60 did nice in Baati and the AML study. SkQ1 shows a lot of promise both systemically and directly as eye drops.
Krill oil ca be spoiled. If you eat a Omega 3 supplements with peroxidized oil content that will be damaging.
One substance I am curious about is heavy water which makes the body fat more resistant to oxidation by electrophiliac substances but that seems to take forever. The makers thought it would have a life extending effect.

Edited by Cosmicalstorm, 15 July 2015 - 10:19 AM.

[niner]

The "antioxidants cause cancer" meme is a little over-done.  Foods rich in antioxidants have long been associated with a reduced cancer risk, which led to trials of antioxidants as chemoprevention agents.  Unfortunately, the antioxidants that they chose were not particularly good- in particular, beta carotene, only a so-so antioxidant in the chemical sense, was used in people at high risk of lung cancer, and appears to have increased their risk.  If you are a smoker and you choose to avoid high doses of beta carotene, I'd say that was a wise decision.  However, you need to look past the term "antioxidant" as applied to beta carotene or the common dietary phenolics like resveratrol.  These things may technically act as antioxidants in a test tube (e.g. the ORAC assay), but in the body they variously act by receptor-based mechanisms or as pro-oxidants, which then upregulate the body's antioxidant defenses in a hormetic fashion.  (1)

 

There is growing evidence that mitochondrial ROS, mainly superoxide, act on spatially co-located proteins, activating signaling pathways that drive the initiation, proliferation, and metastasis of cancer.  (2,3,4)  Mitochondrial antioxidants that can interrupt superoxide formation have been shown to suppress tumor growth, induce tumor apoptosis, and prevent metastasis.  Examples of compounds where this has been seen are MitoTEMPO, MitoQ, and c60oo, the latter in an experiment done in Kelsey Moody's lab, with Longecity as the majority funder.

 

References

 

1) Forman, H. J., Davies, K. J. A. & Ursini, F. How do nutritional antioxidants really work: nucleophilic tone and para-hormesis versus free radical scavenging in vivo. Free Radic. Biol. Med. 66, 24–35 (2014).

2) Nazarewicz, R. R. et al. Does Scavenging of Mitochondrial Superoxide Attenuate Cancer Prosurvival Signaling Pathways? Antioxid. Redox Signal. 19, 344–349 (2013).

 

3) Porporato, P. E. et al. A mitochondrial switch promotes tumor metastasis. Cell Rep. 8, 754–766 (2014).

4) Chandel, N. S. & Tuveson, D. A. The Promise and Perils of Antioxidants for Cancer Patients. N. Engl. J. Med. 371, 177–178 (2014).

[Darryl]

Beta carotene works well as a marker of vegetable intake, and is fine at physical quenching of UV generated singlet oxygen, ie, skin photodamage. However, its a poor chemical reduction antioxidant compared to phenols, so performs poorly on ORAC and similar assays, and is a poor choice for quenching mitochondrial/NOX generated radicals. Supplementation possibly suppresses uptake of other, better carotenoids for UV protection: lycopene for skin, lutein/zeaxanthin/astaxanthin/canthaxanthin for eyes (beta-carotene doesn't pass the blood-retina barrier).

 

Aside from select, limited applications (carotenoids in skin/eyes, ergothionine or synthetic mitochondrial antioxidants, vitamin E for membranes, and < 400 mg/d vitamin C for plasma), I'm dubious that there's much call for direct antioxidants. They appear to interfere with endogenous ROS used in signalling, and probably suppress endogenous antioxidant responses. 

Edited by Darryl, 15 July 2015 - 05:59 PM.

[Dorian Grey]

I'd say most any "essential" vitamin or nutrient will extend lifespan if you're simply not getting enough of one or more of them from dietary sources.  

 

How many have died from scurvy since Hippocrates and the Egyptians first documented it in 1550 BC?  You can run down the list of all essential nutrients and find the diseases and death that have occurred and are still occurring today in the third world.  

 

Modern food fortification has kept many of the more obvious deficiency diseases at bay, but minor to moderate (to major) deficiencies are still occurring in many all around the world.  Some folks ignore this and hope for the best.  Others attempt to eat healthy, but still might not be getting optimal levels of ALL essential nutrients every day.  

 

I lived on junk food, beer and cigarettes for over 25 years during my youth, but also took supplements and apparently have suffered no harm.  I thank god for the various little pills I've popped over the years every day.  

 

 

 

 

 

 

[nowayout]

Metformin has a long list of unpleasant common side effects that makes it somewhat unsuitable for long term use in healthy people: http://www.drugs.com...de-effects.html

 

Rodents may have lived longer, but unfortunately nobody could interview the mice for whether they felt permanent malaise, weakness, heart palpitations, GI issues, flu-like symptoms, frequent infections, rhinitis, etc., etc., and the experience in human diabetics isn't helpful in the context of healthy people, since diabetics are expected to feel non-optimal anyway because of the underlying disease.     

Edited by nowayout, 16 July 2015 - 12:52 PM.

[normalizing]

the side effects seem something i read on almost every drug being sold out there. not sure how it is any special in regard to any serious side effects in low or moderate dose

[pamojja]

Among compounds that extend life in rodents, only aspirin, metformin, and glucosamine have supporting evidence of reduced mortality in humans, though there have yet to be any long-term randomized trials with lifespan as an endpoint.

 

Metformin has a long list of unpleasant common side effects that makes it somewhat unsuitable for long term use in healthy people: http://www.drugs.com...de-effects.html

 

the side effects seem something i read on almost every drug being sold out there. not sure how it is any special in regard to any serious side effects in low or moderate dose

 

Though I do have chronic health issues - and low dose aspirin has been prescribed to me - it's intriguing that I only get adverse reactions from low dose pharmaceuticals, as with these two allegedly harmless and for longevity. As once described in this post:

 

 

http://www.longecity...ndpost&p=606279

• Metformin - appetite reduction and weight gain. Discontinued because of severe nausea and vomiting.
• Aspirin - not used much because of bloody stools repeatedly after only one baby aspirin.

 

Though I found out meanwhile by experimentation that I could prevent at least the bloody stools with phosphatidylcholine. And on a 3rd trial with metformin during a vacation in a high-carb country (like the 2 times before) this time I tolerated it just fine. With the caveat of greatly decreased CoQ10 and halved Vitamin B12 serum levels - and the most paradoxical once a life-time increase of HbA1c form my average of 5 to 6.2% within only 6 weeks (back to normal again).

 

 

http://www.drugs.com...de-effects.html

Hematologic

Very rare (less than 0.01%): Subnormal vitamin B12 levels^[Ref]

 

Though my side-effects seem very rare - not to mention the adverse effects they consider even too rare for considering them worth mentioning - they do make me very cautious of taking aspirin and metformin. Certainly not every one might be as rare as me .

[resveratrol]

Oxaloacetate hasn't been proven in humans yet, but I find the research very convincing.

Edited by resveratrol, 18 July 2015 - 03:52 AM.

[brosci]

Oxaloacetate hasn't been proven in humans yet, but I find the research very convincing.

 

Is 100mg a small dose?  That seems expensive at ~$50 bucks for a bottle.   Looking at citrulline malate, a common dose would supply ~2,300mg of malic acid.  With a dose of magnesium malate on top, it would be up around 5,000mg/d.  I believe malic acid converts to oxaloacetate -- is it superior to take 0.1g of oxaloacetate vs grams of malate?  (Is a Magnesium Oxaloacetate Chelate a possibility?)

Edited by brosci, 18 July 2015 - 04:11 AM.

[Wry]

I revise my statement about calorie restriction (CR) not being shown to be effective in long lived mammals. I have found studies where CR is effective in dogs and monkeys. Perhaps both green tea and resveratrol are benefitial at a young age.

[normalizing]

extending lifespan doesnt seem too good of a thing. it just means, you will be 100 and over and  in very bad shape trying to survive in the modern world that is happining around you at the time. really, look at all the centenarians out there! really old and creepled, barely functioning and have nothing to live for. i remember few of them in interviews wishing to die or having no fear of death. its stupid to live to lets say 120, when you are invalid! might as well look at other ways to live longer but healthier, like transport your body to technology or mind to computers.

 

so, this thread is kind of childish to be honest. no consumption of anything will make you God, but only if you are rich, have the conections and means to acquire later technology is what will give you propably some longer value on earth.

Edited by normalizing, 19 July 2015 - 11:27 AM.

[brosci]

extending lifespan doesnt seem too good of a thing. it just means, you will be 100 and over and  in very bad shape trying to survive in the modern world that is happining around you at the time. really, look at all the centenarians out there! really old and creepled, barely functioning and have nothing to live for. i remember few of them in interviews wishing to die or having no fear of death. its stupid to live to lets say 120, when you are invalid!

 

Perhaps advances in technology will enable a striking difference between the ability to thrive as a 100+ year old in the 2080's vs the 1880's or 1980's.

 

 

 

To get there gracefully, some supplementation might be useful.

Edited by brosci, 19 July 2015 - 02:38 PM.

[Blankspace]

Alas none of the OPs supplements: hormetic Nrf2 activators (organic powder), immunomodulatory (sometimes excessively) β-glucans (reishi), omega-3 EPA (krill oil), carnosase bait (l-carnosine) have much effect on nutrient sensing pathways, and none have extended life in mammals. They seem more likely to offer benefits on stress resistance / reducing inflammation (though the β-glucans are Janus-faced) than affect more fundamental aging progression.

 

Hi Darryl,
Regarding the reishi mushrooms you mentioned the β-glucans, but what are your thoughts on the polysaccharides & triterpenes?  In this thread Krillin referenced a paper (PMID:23468988) that showed reishi can reduce mTor expression. Any thoughts on the use of reishi extract for mTor inhibition?

[Kevnzworld]

Metformin has a long list of unpleasant common side effects that makes it somewhat unsuitable for long term use in healthy people: http://www.drugs.com...de-effects.html

Rodents may have lived longer, but unfortunately nobody could interview the mice for whether they felt permanent malaise, weakness, heart palpitations, GI issues, flu-like symptoms, frequent infections, rhinitis, etc., etc., and the experience in human diabetics isn't helpful in the context of healthy people, since diabetics are expected to feel non-optimal anyway because of the underlying disease.

I am a healthy non diabetic 58yo male. I have taken 500mg of metformin 2x a day for three years due to its well documented anti aging / anti cancer effects. I have felt nothing noticeably negative.
I have begun delaying dosage until later in the day recently so it's AMPK activation effect won't interfere with my morning workout/ Leucine supplementation for muscle preservation.

[Bateau]

Just gonna mention that berberine is a natural alkaloid with very similar effects as metformin with actually more impressive pharmacodynamics than metformin (inhibits PTP1B, augments GLP1, doesn't inhibit B12 absorption or increase risk of Alzheimer's), and has a wide variety of studies showing its efficacy in humans, even outperforming metformin in daibetics and women with PCOS

 

Really a very promising anti-aging supplement.

[ta5]

Just gonna mention that berberine is a natural alkaloid with very similar effects as metformin...

 

Berberine looks great except for the muscle atrophy. 

[Bateau]

Muscle atrophy is a theoretical concern, but not one that will pan out if I were to guess, disregarding unusual circumstances. The study you linked to is an unusual one, I've seen it before and it's the only study out of the hundreds in animals and dozens in humans that has shown muscle atrophy. Berberine generally prevents diabetes induced muscle atrophy, and has even been shown to improve exercise capacity in people after heart failure [1] and strength in diabetics [2, 3]

 

Any catabolic effects berberine has r.e. atrogin-1 will probably be offset by anabolic/anti-catabolic things such as; increased glucose uptake in muscles, increased insulin signalling [through increased insulin sensitivity, increased insulin receptor density, inhibition of PTP1b], increased mitochondrial proliferation & health etc.

 

"Surprisingly, berberine was reported to promote muscle atrophy in both wild-type and db/db mice through hampering mitochondrial function and stimulating the expression of atrogin-1, which promoted protein degradation and suppressed protein synthesis ⁶⁷. However, in another study, berberine improved muscle atrophy, increased glycogen storage and decreased triglycerides content in skeletal muscle of type 2 diabetic rats. Further experiments revealed that reduced expression of CDK9 and cyclin T1 in the muscle was reversed with berberine ⁶⁸. Berberine also increased PPARα/δ expression and reduced PPARγ expression in skeletal muscle similar as rosiglitazone or fenofibrate ⁶⁹. The controversial data may be due to diverse methods of administration. Muscle atrophy was induced by berberine injection. Oral administration of berberine led to improvement of muscle atrophy. The actual effects of berberine remain to be explored"

→ source (external link)

 

My personal anecdote: I take high doses of berberine (1000-1500mg) every day, and have no difficulty consistently gaining muscle size and strength due to my workouts. I am in the first 6 months of heavy exercise (newbie gains) and have always been what the community calls an "easy gainer", so my results are to be expected.

Edited by Bateau, 24 July 2015 - 04:53 PM.

[normalizing]

bateau, which source do you use for the berberine since naturally it is found in very small amounts in few plants and it seems most of it seems highly processed when sold as supplement. it also never specifies the actual source which makes me think it might be synthetic berberine.

[Bateau]

bateau, which source do you use for the berberine since naturally it is found in very small amounts in few plants and it seems most of it seems highly processed when sold as supplement. it also never specifies the actual source which makes me think it might be synthetic berberine.

 

I take Nutri-Thrive's Berberine, since I happen to know the owners of the company. They take their own berberine daily and I trust that their product is good.

 

I did ask once what their berberine was extracted from. I cant remember the exact answer but I want to say it was Amur Cork Tree.

[Darryl]

Another source which I use is Piping-Rock, run by the former owner of Nature's Bounty. They claim their own assay lab, and berberine HCl has a well defined peak in HPLC MS analytical chemistry.

 

Fortunately, hot water extraction of pure berberine from goldthread (Coptis chinensis) roots is fairly simple and has a good yield. Berberine isn't a niche supplement in China, goldthread itself is cultivated as one of the 50 fundamental herbs of Chinese traditional medicine, and the pure compount has become a common local alternative for diabetes treatment. Its cheap enough in China that berberine has been found as an adulterant in Chinese medicines that shouldn't contain it. Barberry (Berberis vulgaris) root/bark is an alternative source, from which its been extracted as yellow dye for milllenia.

 

Berberine is a complex molecule, and although total syntheses have existed since the 60s, they require expensive precursors.

 

 

 

 

 

[ta5]

Surprisingly, berberine was reported to promote muscle atrophy in both wild-type and db/db mice through hampering mitochondrial function and stimulating the expression of atrogin-1...

 

Curcumin could help by inhibiting atrogin-1.

[Bateau]

Another source which I use is Piping-Rock, run by the former owner of Nature's Bounty. They claim their own assay lab, and berberine HCl has a well defined peak in HPLC MS analytical chemistry.

 

 

I've always felt super shady about piping rock. Everything they have is dirt cheap. I tried their digestive enzymes once, since on the label they seemed comparable to a more expensive product I was using, but they seemed to have none of the benefits the other supplements gave me. Didn't help me one bit.

 

Haven't tried anything else from them.

 

You pretty sure they're totally above board Darryl?

[Darryl]

Markups in the retail supplement industry are pretty high. Bulk berberine HCl seems to run $5-20/kg, so its reasonable that Piping Rock can encapsulate $0.25-$1.00 of the powder, randomly check batches for adulterants, and sell for $11 and still make a profit.

 

Even when purchased from laboratory reagent suppliers berberine HCl is only 97-98% pure, with around 20 ppm heavy metals - ie, reasonable for a hot solvent extract from a natural source.

 

I've only bought chemically defined things from Piping-Rock (USP glycine, nicotinic acid, berberine HCl, D3), never enyzmes, probiotics, or ill-defined herbals. Their prices are reasonable given the wholesale costs and the direct-to-consumer model, and their glycine is appropriately sweet, their niacin gives me the proper flush, their berberine has the right colour index. Piping Rock appears to be just a new iteration of a 40 year, three generation family business, so they have strong incentives to maintain quality standards. They're a bit slower in shipping than my other usual supplement sources, Vita-cost and PureBulk, and don't carry some supplements that I prefer, like high-potency K2 M7 and algal-source EPA.