Controlled studies where one group is given Vitamin E and the other a placebo have found no significant harm or benefit at reasonable dose levels:

Three other meta-analyses that combined the results of randomized controlled trials designed to evaluate the efficacy of vitamin E supplementation for the prevention or treatment of cardiovascular disease found no evidence that vitamin E supplementation up to 800 IU/day significantly increased or decreased cardiovascular disease mortality or all-cause mortality (73-75). Additionally, a more recent meta-analysis of 57 randomized controlled trials found that vitamin E supplementation, up to doses of 5,500 IU/day, had no effect on all-cause mortality (76). Furthermore, a meta-analysis of 68 randomized trials found that supplemental vitamin E, singly or in combination with other antioxidant supplements, did not significantly alter risk of all-cause mortality (77). At present, there is no convincing evidence that vitamin E supplementation up to 800 IU/day increases the risk of death from cardiovascular disease or other causes.

[The study] reported that adults who took supplements of 400 IU/day or more were 6% more likely to die from any cause than those who did not take vitamin E supplements (72). However, further breakdown of the risk by vitamin E dose and adjustment for other vitamin and mineral supplements revealed that the increased risk of death was statistically significant only at a dose of 2,000 IU/day, which is higher than the UL for adults.

so perhaps they'll make you stronger - a new vitamin supplementation study demonstrates a "sick-user effect" - those who never took vitamins but suddenly started may have done so because they became seriously ill. This reverses my view based on past studies that multivitamins probably don't help (though I'd continued taking mine, since the evidence was mixed).

During an average 11 years of follow-up, 28,851 deaths were identified. In Cox proportional hazards models controlling for tobacco use and other potential confounders, no associations were found between multivitamin use and mortality from all causes

(for users vs. nonusers:

hazard ratio = 1.07, 95% confidence interval: 0.96, 1.19 for men;

hazard ratio = 0.96, 95% confidence interval: 0.85, 1.09 for women), cardiovascular diseases, or cancer. The findings did not vary across subgroups by ethnicity, age, body mass index, preexisting illness, single vitamin/mineral supplement use, hormone replacement therapy use, and smoking status.

-study

The 1.07 hazard ratio (7% higher chance of dropping dead at any moment) for men is indeed not significant; a simpler model that doesn't control for as many things (including use of some single supplement e.g. selenium) gives a HR=.99, for example.

It's unlikely that vitamins do nothing. Yet they appear to, in this fairly large study of old people. I'd say this is reason to look at fine-tuning vitamin/mineral intake. Those men who took 1-6/week instead of 1x or 2x/day seemed to fare slightly better than 0/week (TOTALLY not significant though).

Too much of some things in diet+multivitamin is likely quite harmful to health. If you ignore statistical significance, the weak evidence is that those old people who take multivitamins for a 5 year stretch are slightly more likely to end up dead 10-15 years later.

Or, supposing that multivitamins aren't harmful (they obviously vary tremendously in composition), it's really true that it's unlikely that your normal diet is lacking anything you need, and the non-significant effect is mostly due to confounds like taking vitamins because you feel your health start to fail, or taking vitamins because you live a healthy lifestyle already, etc.

Unfortunately, that multivitamins do nothing, or are both helpful and harmful, with the harms slightly outweighing the benefits, is the simplest explanation of many such null results in the literature. But I don't want to accept it, because I know of some specific causal evidence suggesting that individual vitamins, when supplemented, yield health benefits in a majority of people. So I'll hold the slightly more complicated: "most multivitamins are too-highly dosing at least a few things, in a way that harms health as much as the rest of it benefits health", tentatively.

Another nearly siginificant pattern: people who've used vitamins for at least 5 years die less than those who recently started or never used (but again, not really significant). Motivated speculation (not wanting to believe multi-vitamins are actually net-harmful or -useless): old people who suddenly start taking multivitamins did so due to correctly feeling their declining health and imminent death. So their higher rate of death shouldn't be blamed on having recently started multivitamins.

Study:

(sadly: of insects, not humans. humans take too long to die?)

Most animals will keep eating until they have enough protein. In some insects, they'll eat up to the level that shortens their lifespan but increases their reproductive output.

increasing the ratio of protein and non-protein energy in the diet decreases lifespan; but as seen in the example from male crickets discussed above, if this ratio falls too far there is an increased risk of decreased longevity associated with obesity

uh-oh. i like my high-protein diet. i need muscles to do well in soccer and volleyball. and it's easy not to overeat when you're not craving protein. this suggests a benefit from titrating protein somehow (being sensitive to how much of it you need for your activity level).

protein intake is more strongly regulated than that of carbohydrate and fat [20]. As a result, protein appetite drives overconsumption of energy on low percent protein diets, promoting obesity and metabolic disorders with consequent effects on longevity

so, be skinny, on as little protein as you can get away with (obviously you'll die with 0 protein in your diet; likewise with 0 fat).

the major causes of increased longevity in studies on calorically restricted primates (most recently [30]) is a reduction in the incidence of diabetes, cancer and cardiovascular disease relative to ad libitum fed controls. This may not result from benefits associated with CR per se, but rather reflect the costs of nutrient imbalance when feeding ad libitum on a fixed diet. As the required balance of nutrients changes over time (with time of day, season, growth and development, and senescence), animals will be forced to overeat some nutrients to gain enough of others

speculation without evidence - they seem to be suggesting that ideally you eat the minimum amount of food necessary for all vitamin / macronutrient needs. but it's also true that if you have excess body fat, you'll survive surgery better. some excess makes you more robust. we can't really titrate perfectly.

i suppose the overall question would be: how much quality of life do you have to sacrifice by risking insufficient intake of various nutrients, in order to maybe live longer? nobody knows the answer for humans, yet.

When protein is eaten in higher then optimal quantities relative to non-protein energy it shortens lifespan - in insects certainly and perhaps too in mammals

yes, perhaps. i hope not, but it needs to be studied - how sensitive is the curve? how "too much" can you do while barely reducing lifespan?

- but what might the underlying mechanisms be? There are several possibilities, including enhanced production of mitochondrial radical oxygen species [19,31], DNA and protein oxidative modification, changes in membrane fatty acid composition and mitochondrial metabolism [19,32], changes in the relationship between insulin/IGF and amino acid signaling pathways, including TOR [33-38], toxic effects of nitrogenous breakdown products and capacity to deal with other dietary toxins [39,40], changes in immune function to pathogen attack [41,42], and changed functioning of circadian systems [43].

(their hypothesis ... AMPK extends life unless you have too much and develop metabolic syndrome (the obesity disease), TOR shortens it.)

insects are quite different than humans. i'm waiting for more evidence that a high-protein-ratio diet shortens life (but i've suspected/feared it for a while)

Phytic acid isn't well understood (at least, its impact on human health isn't), but it's definitely found in many nuts and grains (white flour and rice have far less of it; it's mostly in the hulls/bran), and is good at removing minerals (by chelation) from the human body, e.g. zinc and iron, which is generally bad. On the other hand, it's nice for removing uranium from the body. It also reduces colon cancer. It penetrates the brain and can protect neurons there by chelating iron (which I guess you don't want in the brain - iron does get in there somehow and exacerbates many brain diseases).

Grain consumption has long been known to damage vitamin D status and bone health. Indeed, it is difficult to induce bone frailty in laboratory animals without feeding them grain. In Edward Mellanby’s original experiments leading to the discovery of vitamin D, he induced rickets by feeding dogs a diet of oats or wheat bread. [3] In human infants, wheat bran induces rickets. [4] In addition to interfering with vitamin D, grains also contain high levels of phytic acid, which interferes with bone mineralization by blocking absorption of calcium and magnesium.

source (while making fun of Gwyneth Paltrow's ridiculous macrobiotic diet)

Another crucial factor in bone health is vitamin K2. Since dairy fats are the leading source of vitamin K2, it’s likely Ms. Paltrow was deficient in this crucial vitamin. Most people are deficient in vitamin K2 – let alone those who avoid meats and dairy.  In clinical trials, vitamin K2 supplementation reduced non-vertebral fractures by a remarkable 81%. [5]

reduced by 81% = 1/5 the odds. I like milk. Funny that they thought it was calcium (with supplemented D to aid absorption) that made milk bone-friendly, since it's pretty easy to get enough calcium in general.

a high omega-6 to omega-3 ratio reduces bone density.

omega-6 = vegetable oil (roughly - saturated vegetable oils obviously aren't), omega-3 = fatty cold water fish

The fact that paleo people get excited about phytic acid shows that they're looking for confirmation of their already-held beliefs (grain is bad! etc.)

Fermentation, cooking, and sprouting whole grains, significantly reduce phytic acid content. Almonds and sesame seeds are very high in it; toasting them might help.

It seems like you can benefit from moderate phytic acid (nullifying iron in your brain sounds good), by simply ensuring you have excess of the minerals it chelates and steals from you.

source: http://perfecthealthdiet.com/?p=1177

You need DHA in your diet (EPA can be synthesized from ALA, which is in flaxseed oil; DHA barely can). But high levels of polyunsaturated fats may be dangerous; they're easily oxidized (anecdotal evidence; natural diets don't have high levels, unless they're mostly fish):

You can supplement DHA from some particular type of seaweed (I forget the details), or in many fatty fish or their extracted oil (watch your mercury). It does occur naturally in lesser quantities in various other foods. DHA lowers testosterone, but it has many good effects. Lower testosterone means more (harmless, operable) prostate cancer, but possibly more frequent severe cases:

if DHA is dangerous, low-fat dieters will be in the most trouble. Another reason to eat a high-fat diet.

(the ratio matters; eat more saturated fat to mitigate the harms while still getting some of the benefits of DHA)

Most Americans eat far too much omega-6, and their omega-6 to omega-3 tissue ratio is too high, which is pro-inflammatory via the COX-2 pathway. Eating omega-3s including DHA reduces inflammation by downregulating the COX-2 pathway. This accounts for the well-attested benefits of DHA against cardiovascular disease. Now, cancer is promoted by COX-2 pathway inflammation, which is why COX-2 inhibitors such as aspirin and ibuprofen are protective against cancer. [4] DHA’s action to downregulate this pathway must generate an anti-cancer effect. But, unlike aspirin and ibuprofen, DHA has no observable effect on overall cancer risk. This suggests that DHA has other effects, unrelated to its anti-inflammatory activity, that are cancer promoting. These counterbalance the benefits from its anti-inflammatory effect. If DHA has pro-angiogenic effects that are independent of COX-2 mediated inflammation, then this could account for the observations.

One reason an association of DHA with high-grade cancer may have been missed is that it would be detected only in large studies able to segregate cancers by grade.

 

 a person in whom the immune system is trying but failing to clear elevated CEP levels almost invariably has macular degeneration (AMD)

AMD = why 1/3 of people 75+ yr old are nearly blind. DHA is the only cause of CEP. It's caused by excessive growth of blood vessels dislodging the retina. DHA is concentrated near the retina (is 80% of the PUFA in it). Photons cause oxidation, and DHA is extremely oxidizable. Antioxidants help slow AMD. Finally, adding CEP directly to mice causes AMD (this was shown in 2003). (we know now it's because CEP causes angiogensis).

CEP is normally good. It brings immune cells from bone marrow to the wound. Cancers and AMD give chronic CEP elevation. CEP actually causes wound healing even in mice with normal wound healing mechanisms crippled (VEGF and TLR2 knocked-out or inhibited) - this was shown in 2010. VEGF causes angiogenesis when tissue is oxygen deprived. TLR2 causes angiogenesis when it detects oxidative stress.

vitamin A + DHA yield CEP (via retinyl from A + HOHA=oxidized DHA).

If you're going to take DHA (usually fish oil) you'll want anti-oxidants. Oxidation can't be avoided; it's essential to metabolism and fighting infection.

At the moment, I think it’s prudent to eat no more than 1 pound of salmon or similar cold-water fish per week, to avoid further EPA/DHA supplements, and to avoid low-fat diets which tend to elevate membrane DHA levels. Moderate omega-3 consumption is especially important for those suffering from diseases of pathological angiogenesis – especially cancer. DHA is essential for good health – but in excess, it is probably dangerous.

ouch.

DHA + retinyl + oxidative stress = angiogenesis

This recipe is invoked normally and properly during wound healing. But it is also invoked excessively in pathological contexts – notably in cancers and age-related macular degeneration, probably also in other angiogenesis-associated diseases such as arthritis, rosacea, obesity, psoriasis, endometriosis, dementia, and multiple sclerosis.

 Finasteride raises DHA levels, and DHA lowers testosterone. Low testosterone reduces incidence of low-grade prostate cancers but makes it much more likely they will progress to high-grade. Thus, finasteride reduces prostate cancer incidence but increases high-grade prostate cancer incidence and overall prostate cancer mortality. Fits all the facts. Could be.

source: http://perfecthealthdiet.com/?cat=27

My bottom line: the Brasky study is weak evidence for anything, but it does raise a whiff of evidence that high dietary fish oil intake might encourage a transition from low-grade to high-grade cancer.

Lycopene may be the most powerful carotenoid quencher of singlet oxygen,[18] being 100 times more efficient in test tube studies of singlet-oxygen quenching action thanvitamin E … The absence of the beta-ionone ring structure for lycopene increases its antioxidant action….

Lycopene is not modified to vitamin A in the body …

So lycopene does not increase retinyl levels, but does act as an extraordinarily powerful antioxidant, thus reducing oxidative stress! If you wanted a good food for stopping the DHA – angiogenesis pathway, you’ve found it: tomatoes.

Eat tomatoes. (the other carotenoids mostly can convert to vit A, and overly high levels of vit A mean slightly higher risk of aggressive cancer).

Prostate cancer is associated with low tissue levels of zinc. [7, 8] High dietary intake of zinc is associated with lower rates of prostate cancer. [9]

N-acetylcysteine is an antioxidant supplement that is a precursor to glutathione. N-acetylcysteine has been shown to prevent angiogenesis and has been proposed as a likely cancer preventative, but this is as yet untested. [10]

 Observational studies weakly link high DHA, high vitamin A, and low antioxidant status to diseases of angiogenesis such as cancer.

This pattern would be consistent with the idea that the natural pathway used in wound healing to trigger angiogenesis – DHA oxidation and combination with retinyl protein to trigger TLR-2 pathways – is also important for cancer progression.

It suggests a strategy of reduced fish oil and vitamin A consumption and increased intake of certain antioxidants (such as lycopene, zinc, selenium, or NAC) may be helpful against cancer.

However, this idea needs testing. No study in animal cancer models has tested this dietary combination.

Given the many proven benefits of moderate amounts of fish oil, I don’t see a reason yet to alter our recommendation that healthy people should eat a pound of fish per week. That said, I do think very high intakes of fish or fish oil are ill advised. And I’m intrigued by the idea that dietary changes may have the potential to play a powerful role in recovery from diseases of angiogenesis such as cancer.

A few years ago I started taking a high dose of Omega 3, because of joint inflammation, and other issues. This made big difference for about 3 months, then seemed to not work any more. I talked to a nutritionist friend and she pointed out that according to Andrew Stoll (The Omega 3 Connection) you must take 1000 mg vit C and 500 iu vit E daily or the omega 3 becomes oxidised in your body (cell membranes) and ineffective. I started taking both and in days was back to the original anti-inflammatory effectiveness of omega 3. I have since talked to others about this – for example a psychiatrist whose clients did well on omega 3 for 3 months and then it became ineffective.

quite anecdotal - needs actual research. but the fact that omega-3 are easily oxidized means they might degrade vit-C (which means you need enough carbs+selenium in your diet to move the DHAA out of the bloodstream into cells for reconversion to C, or you just need to bear the harm of DHAA and supplement more C. In general, vit E supplementation is quite harmful. I wouldn't do it unless strong evidence revealed that it's okay when you have high omega-3 intake.

Vitamin C deficiency tends to develop slowly over months, losing a little every day, so it’s quite plausible that a deficiency could develop over 3 months and lead to those changes in omega-3 oxidation.

It is possible that extra lipid peroxidation on a high-PUFA diet could help deplete vitamin C faster.

 

data seem to show that people taking particularly high doses of vitamin E (500 IU to 2000 IU) may have a slightly increased risk of death. However, taking 400 IU vitamin E per day did not increase the risk of death in a total of 15,000 patients studied in several different clinical trials.

source: http://www.nei.nih.gov/news/statements/vitamine.asp

Eating omega-3 fats promotes calcium oxalate kidney stones about as much as eating oxalate. The top quintile of dietary oxalate intake has a relative risk of 1.22. [12]  (The top dietary source of oxalate is spinach, by the way.)

a reminder from my last post:

Zero-carb dieters are at risk for

• Excess renal oxalate from failure to recycle vitamin C;
• Excess renal uric acid from disposal of nitrogen products of gluconeogenesis and ketogenesis;
• Salt and other electrolyte deficiencies from excretion of oxalate, urea and uric acid; and
• Dehydration.

 

If you feed lab animals high doses of polyunsaturated fat (either omega-6 or omega-3 will do) along with high doses of either fructose or alcohol, then fatty liver disease develops along with metabolic syndrome. Metabolic syndrome is a major risk factor for obesity, and it’s not very difficult to induce obesity on these diets.

source: http://perfecthealthdiet.com/?p=1963

Both sugar and vegetable oils are individually risks for obesity:

• Stephan did a nice post a few years back, “Vegetable Oil and Weight Gain,” discussing a couple of studies showing that both rats and humans get fatter the more polyunsaturated fat they eat.
• Dr. Richard Johnson and colleagues did a review of the evidence for sugar (fructose) as a cause of obesity in the American Journal of Clinical Nutrition a few years ago. [1]

What the animal studies show us is that when fructose and vegetable oils are consumed together, they multiply each other’s obesity-inducing effects.

Consistent with this, the obesity explosion in the UK and US is accompanied with dramatic increases (+200% or more) in both polyunsaturated fat and sugar (which is half fructose; roughly the same as high-fructose corn syrup, really).

PUFA (in many vegetable oils) is generally bad even though EPA+DHA are good.

Omega-6 PUFA intake is generally too high in our diet already. When you're losing fat weight, you'll have a lot of omega-6 in your bloodstream assuming you had a normal diet when you put it on, so that means you'd want even less omega-6 in your diet and more omega-3.

In the China Study, the correlation of wheat consumption with BMI was 56%, whereas the correlation of total calorie intake with BMI was only 13%. (Since total calorie intake is correlated with muscle mass, total calorie intake may be completely uncorrelated with fat mass. It’s not how much you eat, but how much wheat!)

Similar outcomes occur in mice. I can’t find any mouse studies comparing wheat to rice, but I did find one comparing wheat to rye [4]. Wheat was far more obesity-inducing than rye:

 

Since rye has gluten, it's not just the gluten in wheat causing obesity (many people vilify gluten, but other than for a minority of people with celiac disease, it's not clear what the problem with it is).

Dietary glucose is not likely to do much damage unless the body’s glucose-disposal machinery has been damaged by other toxins first.

(fructose is a toxin; something in wheat is a toxin); but fructose in a low-carb diet may go straight to glycogen (especially if it's after exercise which drains your muscles' glycogen stores), which is safe. fructose+saturated fat is safer than fructose+PUFA as mentioned above (thank goodness for all that saturated fat in my oversweetened ice cream!)

It’s possible, by the way, that differing toxicities among grains could be responsible for epidemiological evidence favoring “whole grains” over “refined grains.” In America, products made with refined grains are usually 100% wheat; but products made with whole grains are often of mixed origin (“7 grain bread”). Since wheat is the most obesity-inducing grain, dilution of wheat content may be masking the toxicity of whole grains.

 

 I also eat bananas and stone fruits and tend to avoid apples and pears.

(apple+pear are essentially fructose+fiber. fiber may slightly reduce the harm from fructose, but it's still bad)

Beans have a lot of toxins in their raw state. They can sometimes be detoxified by overnight soaking and thorough cooking. With commercial products we don’t really know what they did to process the beans.

I really do think commercial beans are soaked and cooked.

There isn't an obvious minimum required amount of carbs in the human diet.

However, a diet too low in carb+protein calories is definitely bad.

Further, when fighting infection, it's tricky to give your body what it needs if you're not getting enough carbs. Without enough (protein or carbs) you won't get the insulin needed to recycle oxidized vitamin c produced when fighting infection (you can supplement C, but the unrecycled oxidized byproduct is itself harmful). If you must have a near-0-carb diet, you should supplement with NAC, selenium, zinc, copper, coenzyme Q10, ALA, and colorful veggies/berries, especially if fighting infection.

It's almost impossible to make animals carb-deficient; they have large livers (which manufacture glucose) relative to their small brains' glucose needs.

Glucose is needed for immune function and mucus.

If your mucus is low enough, you'll get far more constipation and gut cancers, as do people who've followed the "Optimal Diet" popular in Poland. The reason ulcers and stomach cancers are greatly increased with Helicobacter pylori bacterial infection is that the stomach mucus is severely reduced:

You'll get 100x more kidney stones on an extremely low-carb diet unless you specifically mitigate several factors.

If you're mucus-deficient enough, you'll have dry, bloodshot eyes and dry mouth. If that happens, you definitely need more glucose (meaning more protein possibly, but the simplest solution is to add slightly more carbs). White rice is a safe source of carbs.

source: http://perfecthealthdiet.com/?p=1032

Zero-carb dieters are at risk for

• Excess renal oxalate from failure to recycle vitamin C;
• Excess renal uric acid from disposal of nitrogen products of gluconeogenesis and ketogenesis;
• Salt and other electrolyte deficiencies from excretion of oxalate, urea and uric acid; and
• Dehydration.

These four conditions dramatically elevate the risk of kidney stones.

To remedy these deficiencies, we recommend that everyone who fasts or who follows a zero-carb diet obtain dietary and supplemental antioxidants, eat salt and other electrolytes, and drink lots of water.

Also, unless there is a therapeutic reason to restrict carbohydrates, it is best to obtain about 20% of calories from carbs in order to relieve the need to manufacture glucose and ketones from protein. This will substantially reduce uric acid excretion. If it also reduces vitamin C degradation rates, as we argued in 

our last post, then it will substantially reduce oxalate excretion as well.

The argument that carbs (or at least insulin, which you can get by eating a lot of protein also) help clear out degraded vitamin C is partially anecdotal, but seems reasonable to me:

• An infection or some other stress (e.g. injury, cancer) leads to the oxidation of extracellular vitamin C; and
• On a low-insulin or glutathione-deficiency-inducing diet, oxidized vitamin C is not recycled.

The immune response to infections generates reactive oxygen species, which oxidize vitamin C. Oxidation removes a hydrogen atom from vitamin C, turning it into “dehydroascorbic acid,” or DHAA. If DHAA remains in the blood, it degrades with a half-life of 6 minutes. [3]

Infections can cause vitamin C deficiency on any diet. During the “acute phase response” to infection or injury, vitamin C often becomes deficient. Here is a nice paper in which French doctors surveyed their hospital patients for scurvy:

We determined serum ascorbic acid level (SAAL) and searched for clinical and biological signs of scurvy in 184 patients hospitalized during a 2-month period.

RESULTS: The prevalence of hypovitaminosis C (depletion: SAAL<5 mg/l or deficiency: SAAL<2 mg/l) was 47.3%. Some 16.9% of the patients had vitamin C deficiency. There was a strong association between hypovitaminosis C and the presence of an acute phase response (p=0.002). [4]

So half were at least depleted in vitamin C and 17% had outright deficiency, which if it persisted would produce scurvy.

DHAA can be recycled back into vitamin C, but only inside cells.

DHAA transport is crucial for brain vitamin C status. There is no direct transport of vitamin C into the brain, yet the brain is one of the most vitamin C-dependent tissues in the body.

Supplying DHAA to stroke victims (of the mouse persuasion) as late as 3 hours after the stroke can reduce the stroke-damaged volume by up to 95%:

DHA (250 mg/kg or 500 mg/kg) administered at 3 h postischemia reduced infarct volume by 6- to 9-fold, to only 5% with the highest DHA dose (P < 0.05). [7]

Once inside the cell, DHAA is recycled back to ascorbate, mainly by glutathione inside mitochondria

Glutathione is recycled mainly by an enzyme built with selenium. Zero-carb diets deplete selenium levels. Once that happens, you'll have a Glutathione deficiency. (NAC is a Glutathione precursor, thus the recommendation to supplement if low-carb, especially if ill. You can also directly supplement Glutathione, taken with lots of water and no food).

source: http://perfecthealthdiet.com/?p=1139

Vitamin C supplementation while ill makes sense, but you definitely want to have enough insulin and glutathione to recyle it to avoid the damage its "used" version creates:

In 1970, I discovered that the sicker a patient was, the more ascorbic acid he would tolerate by mouth before diarrhea was produced. At least 80% of adult patients will tolerate 10 to 15 grams of ascorbic acid … The astonishing finding was that all patients … can take greater amounts of the substance orally without having diarrhea when ill or under stress. [5]

Extremely high dose intravenous vitamin C is effective in some cases.

The patient tries to TITRATE between that amount which begins to make him feel better and that amount which almost but not quite causes diarrhea. [5]

Recall that in animals, vitamin C synthesis rises as much as 100-fold under disease. In humans, the limit of bowel tolerance rises up to 20-fold during illness. This suggests that bowel tolerance limit is an indicator of need.

Maybe. Bowel tolerance may be well over the optimum. But if it's too hard to predict the optimum, it may be better than some fixed, modest amount.

 it is my experience that ascorbate has little effect on the primary fungal infections

Well-nourished humans usually contain not much more than 5 grams of vitamin C in their bodies….

If a disease is toxic enough to allow for the person’s potential consumption of 100 grams of vitamin C, imagine what that disease must be doing to that possible 5 grams of ascorbate stored in the body. A condition of ACUTE INDUCED SCURVY is rapidly induced.

Nah. Maybe the 100g tolerated is quickly pissed/shit out. But say only 90% of it is wasted excess - then his point still carries weight.

Speculation: it's possible that Vit C is useful/protective against the poisonous ROS byproducts of the immune response, at a rate that exceeds the maximum recycling bandwidth via whatever (insulin+glutathione) is available. In that case, maybe the harm of the degraded Vit C is worth bearing.

Conventional wisdom is correct in that only small amounts of vitamin C are necessary for this [antioxidant] function because of its [recycling and] repeated use. The point missed is that the limiting part in nonenzymatic free radical scavenging is the rate at which extra high-energy electrons are provided through NADH to re-reduce the vitamin C and other free radical scavengers. When ill, free radicals are formed at a rate faster than the high-energy electrons are made available. Doses of vitamin C as large as 1-10 g per 24 h do only limited good. However, when ascorbate is used in massive amounts, such as 30-200+ g per 24 h, these amounts directly provide the electrons necessary to quench the free radicals of almost any inflammation. Additionally, in high concentrations ascorbate reduces NAD(P)H and therefore can provide the high-energy electrons necessary to reduce the molecular oxygen used in the respiratory burst of phagocytes. In these functions, the ascorbate part is mostly wasted but the necessary high-energy electrons are provided in large amounts.

I guess my speculation above is right.

Another early view was that vitamin C helps by destroying histamine, which may be produced in excess under conditions of stress.

"early view"? sounds like it's not a good view :)

the oxidized form of vitamin C, dehydroascorbate, has strong antiviral activity in vitro.

DHAA is the (harmful) used vit-C byproduct that's normally recycled.

 in clinical experience, vitamin C is most effective against viral infections.

Since animals upregulate ascorbate production under all kinds of stress, not just viral infections, it seems probable that vitamin C aids health by multiple pathways, not only by antiviral activity.

Vitamin C is extremely safe. Intravenous doses of 120 g/day given to cancer patients have been well tolerated.

In animals such as chickens that lack the ability to synthesize vitamin C, vitamin C is recognized as a means of supporting bacterial and viral immunity.

A well-tested therapeutic strategy would be to take 4 g vitamin C every hour with water until bowel intolerance is reached. The therapy is extremely safe, and its effectiveness is usually apparent within days.

Supposedly low iodine and D are common with prolonged infections. Maybe selenium (may just be in case of low-carb). Meat has plenty of selenium, of course.

Daily supplementation with high vit-C while not ill has some preliminary contraindicative research. Over-supplementing with vitamin E (fat soluble and toxic) is definitely bad. C might be ok.

(a) The Ristow paper administered vitamin E along with the C, see below for issues with that.

(b) Suppression of glutathione peroxidase and zinc-copper superoxide dismutase levels by C supplementation could be dependent upon levels of selenium and copper intake; so far only a small part of “supplement space” has been explored. What would be the effect of co-supplementation of C with selenium and copper?

(c) I can easily believe that vitamin C reduces the stress of exercise, but why isn’t the response to that more intense exercise, rather than elimination of vitamin C? Isn’t better tolerance of exercise a benefit for athletic training?

I’m not denigrating these papers, there could be reasons to avoid routine gram doses of C. But it needs more research. The benefits of C at 500 mg to 1 g/day in healthy people are more well established than these possible harms.

(2) The higher death rates are mainly in trials with vitamin E, sometimes beta carotene, both of which raise death rates on their own. When vitamin C is trialled on its own, the results have been mixed, but on my reading net positive.

In the case of C, our advice is more precautionary. Deficiency is tremendously harmful, but excess is virtually harmless. In trials, the benefit may be non-existent for 95%, but 5% may see big benefits and 0% harm. In trials the 95% dilute the benefits to the 5% out of statistical significance. Since the greatest benefit is likely to come in preventing infections from taking root, and everyone gets exposed to pathogens from time to time, we can’t know which of the 100% will benefit from the supplementation. So it makes sense to take a prophylactic supplement.

E and beta carotene seem to do damage. C and glutathione are essentially similar in status, C recycles glutathione and glutathione recycles C, so supplementing C is the most straightforward way to improve glutathione status. I happen to think glutathione is extremely beneficial and this is part of the reason I support C supplementation.

I do think you need a balance of the natural antioxidants, which is why copper and zinc (for zinc-copper superoxide dismutase) and selenium (for glutathione peroxidase) supplementation, and avoiding iron deficiency (for catalase), are important along with C supplementation.

We recommend obtaining vitamin E from foods only. If supplements are taken, they should supply low doses of mixed tocopherols and tocotrienols, not alpha-tocopherol only.

NAC we recommend for treating infections, not otherwise.

(NAC is popular in bodybuilding supplements, most of which do nothing to grow muscle - the legal ones, at least)

C and selenium and a good diet, NAC in infections, should be sufficient to make liver glutathione.

Plant antioxidants I would avoid. I think the natural, mitochondrial antioxidants are going to be more beneficial than food antioxidants that don’t penetrate mitochondria (where antioxidants are most needed) and that suppress ROS signaling.

weird. C is a plant antioxidant. carotenoids also (-> vit A) which give healthy (yellow-orange) looking skin and help immune function and neuron function. He must mean some other plant antioxidants (either tocopherols (vitamin-E like), polyphenolics (e.g. in balck tea, raspberries), or terpenoids (aromatic oils - citral, menthol, camphor, cannabinoids)?)

source: http://perfecthealthdiet.com/?p=636

Ignoring the superstitious pseudo-evolutionary constellation of beliefs associated with it, I think "paleo" believers are doing a good job noticing severe flaws in conventional diet and health advice. The main dietary themes seem to me: plenty of protein is good, saturated animal fat is good, non-contaminated fish are good, colorful vegetables are good, high carbs (as far as it causes high insulin or appetite) is bad, fructose is bad (oddly, they usually recommend fruits anyway, especially berries), nuts+avocados are good, grains are bad (they're divided on that; some people legitimately suffer from grains - tubers/squashes instead), full-fat and/or fermented dairy is better than low-fat (also divided; over half the world is lactose intolerant, so non-fermented dairy would be a bad idea for them), and, in terms of supplementation: plenty of DHA (fish oil) and vitamin D (sunlight or pills), otherwise RDA plus a little.

It’s very easy to induce obesity in both animals and humans: feed a malnourishing diet providing calories in the form of a combination of wheat, fructose, and polyunsaturated fats.

- http://perfecthealthdiet.com/
(presumably he means omega-6 polyunsaturated fats, and not EPA/DHA (omega-3))

An interesting paleo dissent (in favor of high-carb, low-fat, low-meat eating). Probably healthy enough but it won't support intense physical activity.

Some smart folks have noticed that you have at least initial success with low-food-reward calorie consumption (basically: don't combine a source of calories with something that's fun to eat). e.g. Seth Roberts

This guy dissents:

• I think the focus should be on recovering health by curing metabolic damage.
• I think our evolved preference for tasty foods including starches, fat, salt, and other “high reward” flavors indicates they are healthy, and therefore that a diet rich in such foods is most likely to cure metabolic damage.
• I think it is essential to stay away from toxic, malnourishing foods made from wheat, fructose sugars, omega-6 oils, and bioactive compounds like MSG; and instead to eat foods that accord with our evolutionary history.

By metabolic damage, he means one of many possible things that can go wrong, with fat cells, the brain, hormones, whatever (really yet to be completely discovered). He objects to focusing on food-reward because he thinks that the fact that low-reward diets' initial effectiveness is almost never sustained. By the way, the concept of "metabolic damage" being responsible for obesity is controversial amongst the "fat people have no willpower" crowd, but clearly diabetes fits the description.

Don't supplement with too much calcium. Not only does high calcium prevent bone turnover (which you want), but it prevents magnesium absorption (oddly enough, supplementing magnesium will also help calcium reach bones).

high calcium intake can reduce the enlargement of the appendicular bones that generally occurs with ageing as a mechanical compensation for a decline in bone mineral density. Furthermore, high calcium doses slow bone turnover and also reduce the number of active bone remodelling sites. This situation can lead to a delay of bone repair caused by fatigue, and thus increase the risk of fractures independent of bone mineral density.

The highest quintile of calcium intake did not further reduce the risk of fractures of any type, or of osteoporosis, but was associated with a higher rate of hip fracture, hazard ratio 1.19 (1.06 to 1.32).

20% higher risk! Huge. A U-shaped dose/response curve is common in most vitamins (except those that can be pissed out easily, mostly water soluble like Vit B)

 - Dietary calcium intake and risk of fracture and osteoporosis: prospective longitudinal cohort study.

(HT)

Also:

Most people probably get insufficient amounts of dietary magnesium, but it’s one of the most important minerals for overall general health, including the stress response system. It’s nigh impossible to overdose (you’ll just have to hit the toilet), making it very safe to supplement – so do it! Take some magnesium if you aren’t eating leafy greens and nuts on a regular basis.

Excessive cortisol is the bad guy, obviously, and black tea has been shown to reduce stress, lower stress-induced cortisol, and increase relaxation when compared to placebo.

L-Theanine, which is present in green tea leaves, has anti-stress properties, most likely by inhibiting cortical neuron excitation. This goes for both psychosocial and physiological sources of stress. Take some L-Theanine in addition to the green tea.

(L-Theanine does the opposite of caffeine; but coffee is good for you overall). If you're already too agitated, I guess it might help.
(HT)

Take Phosphatidyl Serine

If there is one supplement I’d recommend for its stress mitigating effects this would be it. The body doesn’t make much of it and we don’t get much from our diets, but its particularly concentrated in and is vital to the healthy functioning of nerve cell membranes. And get this: stress depletes it. PS is one of those 21st century hacks I’m always on the lookout for. It works on both mental and physical stress; improving mood and blunting cortisol after physical exercise.

Looks like the evidence for memory/cognition improvement is extremely weak, but the evidence for athletic performance (better recovery and reduced stress in competition) is good.

PS can be found in meat, but is most abundant in the brain and in innards such as liver and kidney. Only small amounts of PS can be found in dairy products or in vegetables, with the exception of white beans.

Food	PS Content in mg/100 g
Bovine brain	713
Atlantic mackerel	480
Chicken heart	414
Atlantic herring	360
Eel	335
Offal (average value)	305
Pig's spleen	239
Pig's kidney	218
Tuna	194
Chicken leg, with skin, without bone	134
Chicken liver	123
White beans	107
Soft-shell clam	87
Chicken breast, with skin	85
Mullet	76
Veal	72
Beef	69
Pork	57

fasting was also found to reduce other cardiac risk factors, such as triglycerides, weight, and blood sugar levels...

 

HGH works to protect lean muscle and metabolic balance, a response triggered and accelerated by fasting.During the 24-hour fasting periods, HGH increased an average of 1,300 percent in women, and nearly 2,000 percent in men.

(HGH is abused by some bodybuilders and is of questionable benefit in actually growing huge muscles)

 - Routine Periodic Fasting Is Good for Your Health, and Your Heart, Study Suggests

Potentially crackpot (no research cited) claim for improving low testosterone via diet:

• Restrict sugar
• Eat foods that inhibit aromatase (to limit oestrogen conversion)

(mushrooms and vitamin C inhibit aromatase - again, no study cited)

• Eradicate trans fats (via elimination of vegetable oils)
• Eat more fat - well less PUFA and more SFA

Fine. Butter is good for you. But EPA and DHA (Omega-3 and thus PUFA) are necessary in the diet.

• Eat foods that are rich in vitamins A+K (meat, butter, eggs, organs)
• Boost vitamin D

I started to get a little body acne after supplementing with 4000 IU D daily (especially once I started getting an hour of sun daily). I figured that was due to excess D (it's fat soluble and so a dose that was fine for a few weeks may be too much once you're saturated) but perhaps it was just giving me steroid-like side effects :) In any case, I cut back on the D supplementation (you can't get too much D from sun, fortunately - the body scales back when it's not needed).

Don't worry yet about high-Choline diet causing high markers for heart disease.

(could be motivated cognition causing him to conclude "keep eating eggs and liver", but there is a lot of evidence that insufficient Choline makes you dumber)

Men tend to think women find bulkier men attractive than what women generally find attractive (Frederick et al. 2005)

(evolvify - overuse of evo-psych story-time thinking warning). Yep. Marketing and a desire for high status; confusing physical power for it (not really the case in modern civilizations).

Humans are also good at assessing strength based on the face alone ... subjects were just as good at judging strength from the faces of men of other cultures as from their own

Overall, body attractiveness was a better predictor of self-reported mating success than facial attractiveness. In line with our main hypothesis, we found a positive relationship between a composite measure of men’s physical fitness (PF) and men’s body attractiveness. This was obtained not only for aggregated attractiveness ratings but also for all 27 female raters individually. This finding is remarkable because individual attractiveness judgments reflect a strong idiosyncratic component, at least for faces. Attractiveness judgments were made fast and effortless. The strength of the attractiveness-fitness relation- ship obtained here suggests that signalling physical fitness may be one of the key functions of male attractiveness.” (Honekopp et al. 2006)

fitness, not bodybuilder bulk.

Multiple studies have confirmed that women are overwhelmingly more likely to cheat on their partner during the two or three days of ovulation. During this time, hormones alter a woman’s behavior to the point thatotherwise rational and emotional arguments against cheating are fundamentally altered. Emotions, culture, and society may be telling her that cheating is bad, but her body is telling her to mate with the best man she can get. Here’s the rub: The idea of what constitutes “the best man” also changes during that time.

(high-fitness, more "manly" men are sexier when a woman is fertile; she wants those good genes)

Conventional wisdom aside, it's generally thought that people universally prefer lighter skin and (lesser known) yellower skin, which is a sign of high carotenoids, which are a sign for (cause of, probably) a healthier immune system. So it would make sense that people instinctively prefer yellower skin. Perhaps the fake orange tan is more attractive than a real tan, mockery of Jersey Shore notwithstanding. Anyway, it turns out that the yellow-skin preference is much stronger than the light-skin preference. Perhaps vegans are attractive after all, in spite of their low-protein diet and thus low-muscle body.

However, we have to trust that the photoshop color adjustment of face photos is faithful to actual tanning and high-carotenoid skin responses.

a higher skin content of carotenoids may reduce both the tendency to burn and the need and production of melanin

(anecdotal evidence) (HT)

Left, sun tan; center, neutral; right, carotene-rich

People consuming diets rich in carotenoids from natural foods, such as fruits and vegetables, are healthier and have lower mortality from a number of chronic illnesses.^[3] However, a recent meta-analysis of 68 reliable antioxidant supplementation experiments involving a total of 232,606 individuals concluded that consuming additional β-carotene from supplements is unlikely to be beneficial and may actually be harmful,^[4] although this conclusion may be due to the inclusion of studies involving smokers.^[5] With the notable exception of Vietnam Gacand crude palm oil, most carotenoid-rich fruits and vegetables are low in lipids. Since dietary lipids have been hypothesized to be an important factor for carotenoid bioavailability, a 2005 study investigated whether addition of avocado fruit or oil, as lipid sources, would enhance carotenoid absorption in humans. The study found that the addition of both avocado fruit and oil significantly enhanced the subjects' absorption of all carotenoids tested (α-carotene, β-carotene, lycopene, and lutein).^[6]

(Wikipedia)

Carotenoids (tetraterpenoids)

Carotenes - orange pigments

α-Carotene – to vitamin A, in carrots, pumpkins, maize, tangerine, orange.

β-Carotene – to vitamin A, in dark, leafy greens and red, orange and yellow fruits and vegetables.

Lycopene – Vietnam Gac, tomatoes, grapefruit, watermelon, guava, apricots, carrots, autumn olive.

Phytofluene – star fruit, sweet potato, orange.

Phytoene – sweet potato, orange.

Xanthophylls - yellow pigments.

Canthaxanthin – paprika.

Cryptoxanthin – mango, tangerine, orange, papaya, peaches, avocado, pea, grapefruit, kiwi.

Zeaxanthin – wolfberry, spinach, kale, turnip greens, maize, eggs, red pepper, pumpkin, oranges.

Astaxanthin – microalge, yeast, krill, shrimp, salmon, lobsters, and some crabs

Lutein – spinach, turnip greens, romaine lettuce, eggs, red pepper, pumpkin, mango, papaya, oranges, kiwi, peaches, squash, legumes, brassicates, prunes, sweet potatoes, honeydew melon, rhubarb, plum, avocado, pear.

Rubixanthin – rose hips.

Basically, any colored fruit or vegetable (maybe clorophyll is so strong that you can't really see the orange or yellow pigment - it just makes the result look "dark green")

Carotenoids are fat-soluble so we must consume fats with carotenoid-rich foods to optimize carotenoid absorption.

I didn't realize that fat-soluble meant you absorb it better when you have fatty acids from diet (in bloodstream? in digestive tract?). But I checked and it seems to be conventional wisdom. I thought fat-soluble only meant that you'd store it in your fat cells and thus release it when you burn fat for calories (that must be true).