Search Results for: fungal infections

Tryptophan Poisoning and Chronic Infections

On Friday I discussed a recent paper showing that a high-tryptophan diet caused mice, after 4 to 12 weeks, to start harming themselves by tearing out fur from their bellies and forepaws. The mice also developed ulcerative dermatitis – open sores on their skin. [1]

I closed with a promise that on Monday I would suggest some reasons why a high tryptophan diet might cause these diseases.

However …

C57BL/6 Mice Are Prone to Ulcerative Dermatitis

The breed of mice used in the study, C57BL/6 mice, are an inbred strain featuring some genetic mutations which make them prone to ulcerative dermatitis and compulsive behavior.

Upon looking into the literature, it seems that if you look at these mice cross-wise they get ulcerative dermatitis.

For instance, vitamin A causes ulcerative dermatitis in these mice because of mutations that impair the disposal of excess retinol:

A number of C57BL/6 (B6) substrains are commonly used by scientists for basic biomedical research. One of several B6 strain-specific background diseases is focal alopecia that may resolve or progress to severe, ulcerative dermatitis…. Four B6 substrains tested have a polymorphism in alcohol dehydrogenase 4 (Adh4) that reduces its activity and potentially affects removal of excess retinol. Using immunohistochemistry, differential expression of epithelial retinol dehydrogenase (DHRS9) was detected, which may partially explain anecdotal reports of frequency differences between B6 substrains. The combination of these 2 defects has the potential to make high dietary vitamin A levels toxic in some B6 substrains … [2]

Malnourishment seems to lead to spontaneous development of ulcerative dermatitis. The cause may be oxidative stress, since supplemental vitamin E cures the ulcerative dermatitis:

In this study, we fed a standard NIH-31 diet fortified with vitamin E to C57BL/6 mice and strains of mice with a C57BL/6 background that had spontaneously developed ulcerative dermatitis (UD)…. Of 71 mice, 32 (45%) had complete lesion re-epithelialization with hair regrowth. Complete lesion repair was not influenced by sex, age, or coat color. The average time to complete lesion repair ranged from 2 to 5 weeks, and there was no correlation with sex or coat color. The positive response to vitamin E suggests that protection from oxidative injury may play a role in the resolution of UD lesions … [3]

When scientists studying cancer applied a carcinogenic toxin to the skin of these mice, they developed not cancer but – you guessed it – ulcerative dermatitis:

In this study, heterozygous p53-deficient (p53(+/-)) mice … and wild-type (WT) litter mates were subjected to a two-stage skin carcinogenesis protocol with 7,12-dimethylbenz[a]anthracene and 12-O-tetradecanoylphorbol-13-acetate. Instead of skin carcinomas, however, the chemical treatment protocol caused ulcerous skin lesions, and 89% of mice fed ad libitum died from infection/septicemia. When WT mice were restricted to 60% of the average calorie intake of the respective ad libitum group, however, only 33% developed such lesions, and the CR mice survived twice as long on average as the ad libitum mice. [4]

It’s interesting that calorie restriction reduces the ulcerative dermatitis rate. Note that the mice went on to die of sepsis from an unknown infection; this suggests that these mice probably had some chronic pre-existing infection that was laying dormant, but emerged to become acute when the mouse was stressed by the toxins.

So far we’ve seen that malnutrition (lack of antioxidants) and exposure to toxins (vitamin A, carcionogens) can cause ulcerative dermatitis. Our three major causes of disease are malnutrition, toxins, and pathogens, so to complete our survey we should check whether infections cause ulcerative dermatitis in these mice.

Indeed they do. The most common infection in laboratory mice is fur mites, and fur mite infections induce ulcerative dermatitis in all strains of C57BL mice. [5]

Since diseases become more common with age, we shouldn’t be surprised to see that the rate of spontaneous ulcerative dermatitis rise with age in these mice:

A spontaneous, severely pruritic ulcerative dermatitis was initially observed in 33/201 (16.4%) aged C57BL/6NNia mice obtained from the National Institute of Aging. This ulcerative dermatitis also developed in 21/98 (21%) aged C57BL/6 mice in a subsequent experimental group obtained from the same source. The average age of onset in the initial group was 20 months. These animals were negative for ectoparasite infestation and primary bacterial or fungal infection. The lesions varied from acute epidermal excoriation and ulceration to chronic ulceration with marked dermal fibrosis…. The elucidation of the pathogenesis of this disease is important because of the significant percentage of animals affected … [6]

Given that there are so many possible triggers of ulcerative dermatitis in these mice, I decided to shift the topic of this post a bit, and focus on the specific possibility that chronic infections might play a role.

Lab Mice Are At Risk For Chronic Infections

As I’ve said many times, everyone gets chronic infections. The world is saturated in germs, and sooner or later the ones that can maintain persistent infections take up residence in all of us. So health is determined by the relative balance of power between immune system and pathogens, not by exposure.

Lab mice are at heightened risk for chronic infections because of their living conditions. In the case of the tryptophan-poisoned mice, here’s a description of their accommodations:

All subjects were adult (over 6 months of age) C57BL/6 mice, bred from C57BL/6J progenitors, and housed with same-sex siblings…. Lights were on a 14-10-h light-dark cycle. Mice were caged in standard shoebox cages (12.7 cm high, 433 cm2 floor area) with wire lids…. Ages ranged from 24-66 weeks of age (mean, 47 weeks). The number of mice per cage was variable, ranging from 2-4 mice per cage. [1]

These shoebox cages are small: 433 cm2 floor area translates to roughly 15 by 29 cm or 6 by 11 inches. The lid is 5 inches high. With four mice to a cage, each mouse gets a 3 by 5 inch area.

There is little room to exercise. Crowding is stressful.

Moreover, there is no natural sunlight, and therefore no vitamin D production.

All of these factors tend to impair immune function. Their casein, cornstarch, and soybean oil diets can’t be helpful to immune function either.

Cages are generally fairly closely packed in animal facilities. The mice generally cannot touch mice in adjacent cages, but respiratory pathogens and fur mites spread easily. If one mouse in a facility gets fur mites, usually all the others get infected soon afterward, and the whole room has to be quarantined.

Note also that the mice are old enough – 6 to 15 months – to have had extensive exposure to any chronic pathogens carried by either their mouse neighbors or their human handlers.

So it wouldn’t be surprising if the lab mice in this study had chronic infections.

Chlamydiae Infections in Lab Mice

C. pneumoniae is a zoonotic bacterium that crossed from reptiles to mammals about 60 million years ago and can infect both humans and animals.

Unfortunately, nobody seems to have bothered to see if C. pneumoniae is commonly present in “healthy” lab mice. However, in test tubes C. pneumoniae infects mouse brain cells just fine:

Inspired by the suggested associations between neurological diseases and infections, we determined the susceptibility of brain cells to Chlamydia pneumoniae (Cpn). Murine astrocyte (C8D1A), neuronal (NB41A3) and microglial (BV-2) cell lines were inoculated with Cpn…. Our data demonstrate that the neuronal cell line is highly sensitive to Cpn, produces viable progeny and is prone to die after infection by necrosis. Cpn tropism was similar in an astrocyte cell line, apart from the higher production of extracellular Cpn and less pronounced necrosis. In contrast, the microglial cell line is highly resistant to Cpn as the immunohistochemical signs almost completely disappeared after 24 h. Nevertheless, significant Cpn DNA amounts could be detected, suggesting Cpn persistence. [7]

So in the mouse glial cells which were most resistant, C. pneumoniae could maintain infections even if it didn’t do much. In mouse neurons and astrocytes, C. pneumoniae was able to reproduce freely and would eventually kill the cells.

In a different mouse microglial cell line, EOC-20, C. pneumoniae replicates rapidly, increasing 9-fold in 3 days. [8] So it appears that C. pneumoniae can infect all the major cell types of the mouse brain.

In humans, C. pneumoniae generally reaches the brain by first infecting the blood vessels that feed the brain. In our C57BL/6 mice, C. pneumoniae can create a vascular infection after a single dose in the nose:

In C57BL/6J mice on a nonatherogenic diet, C. pneumoniae were detected in the aorta only 2 weeks after a single intranasal inoculation in 8% of mice. The persistence of C. pneumoniae in atheromas suggests a tropism of C. pneumoniae to the lesion. [9]

Repeated inoculation of C57BL/6J mice resulted in inflammatory changes in the heart and aorta in 8 of 40 of mice … [10]

In a ranking of mouse strains in susceptibility to C. pneumoniae infection, C57BL/6 mice occupy a middle position:

The first mouse models for C. pneumoniae infection … used several mouse strains that differed in susceptibility to infection. Swiss Webster mice and NIH/S mice were highly susceptible, followed by C57BL/6 mice, whereas BALB/c mice were least susceptible. [11]

C. pneumoniae infection typically begins with a brief, mild respiratory infection that is followed by spread of the pathogen to other organs via infected white blood cells and establishment of a persistent infection:

Infection of mice with C. pneumoniae resulted in a self-limiting pneumonia [30–32,77]. Depending on the dose given, mice displayed symptoms, like dyspnea, weakness and weight loss. The symptoms reached a maximum within 2 to 4 days and rarely lasted longer than 1 week….

Isolation of viable C. pneumoniae organisms from the lungs was generally possible up to 4 weeks after infection and occasionally up to 6 weeks [31,32,42,47,49,52,54,66,72]. However, C. pneumoniae antigens and DNA were detected in the lungs for a much longer period, up to 20 weeks after infection [42]. The presence of C. pneumoniae antigens in the lungs was limited to macrophages in alveoli and bronchus-associated lymphoid tissue [63]. These findings suggested a latent persistence of the organisms, which was confirmed by reactivation of pulmonary infection using cortisone-induced immunosuppression experiments [50,51]….

C. pneumoniae infection was not limited to the respiratory tract only. Following local infection, spreading of C. pneumoniae to multiple organs throughout the body was detected by PCR and immunohistochemical staining up to 20 weeks [42]. The dissemination was probably mediated by peripheral blood monocytes as they were positive both by PCR and isolation in some studies, whereas blood plasma was negative [38,47]. [11]

Interferon Gamma and the Immune Defense Against Chlamydiae

In both humans and mice, immune defense against Chlamydiae is mediated principally by interferon gamma. Mice that lack interferon gamma or its receptor suffer prolonged severe infections:

The central role of IFN-? in clearance is evidenced by prolonged infections that occur in IFN-?, and IFN-? receptor-, deficient mice (10, 11). [12]

Infant mice exposed to Chlamydiae die within 2 weeks if they lack interferon gamma:

Importantly, infected mice deficient in IFN-gamma or IFN-gamma receptor demonstrated enhanced chlamydial dissemination, and 100% of animals died by 2 wk postchallenge. [13]

Might Chlamydia Infection Have a Connection to Compulsive Behavior and Ulcerative Dermatitis?

I started looking into these Chlamydia infection papers to see if they might explain why C57BL/6 mice given high levels of tryptophan might develop compulsive behavior and ulcerative dermatitis.

It’s possible. The logic goes like this.

First, tryptophan is crucial to Chlamydial growth; it is a precursor to niacin, the key vitamin of bacterial metabolism, and is also essential to a number of Chlamydial proteins. So a high-tryptophan diet will promote Chlamydiae infections.

Chlamydiae trigger the innate immune response mediated by interferon gamma.

So interferon gamma will be elevated in Chlamydiae-infected mice. Interestingly, the only study I found that gave interferon gamma directly to mice found that it caused ulcerative dermatitis:

Daily subcutaneous doses of 0.02, 0.2, or 2 mg/kg/d of recombinant murine interferon-gamma (rmuIFN-gamma) were given to mice on postnatal days 8 through 60 … Males given 0.2 and 2 mg/kg/d had swelling and ulcerative dermatitis around the urogenital area, which were observed after sexual contact and attributed to a bacterial infection. [14]

What about the compulsive behavior? Well, in mice one of the principal effects of interferon gamma is to stimulate the release nitric oxide (NO):

Gamma interferon (IFN-gamma)-induced effector mechanisms have potent antichlamydial activities that are critical to host defense. The most prominent and well-studied effectors are indoleamine dioxygenase (IDO) and nitric oxide (NO) synthase. The relative contributions of these mechanisms as inhibitors of chlamydial in vitro growth have been extensively studied using different host cells, induction mechanisms, and chlamydial strains with conflicting results. Here, we have undertaken a comparative analysis of cytokine- and lipopolysaccharide (LPS)-induced IDO and NO using an extensive assortment of human and murine host cells infected with human and murine chlamydial strains. Following cytokine (IFN-gamma or tumor necrosis factor alpha) and/or LPS treatment, the majority of human cell lines induced IDO but failed to produce NO. Conversely, the majority of mouse cell lines studied produced NO, not IDO. [15]

That’s interesting, because nitric oxide (NO) induces compulsive behavior in mice. A standard measure of obsessive-compulsive behavior in mice is marble burying. Nitric oxide increases marble burying:

In view of the reports that nitric oxide modulates the neurotransmitters implicated in obsessive-compulsive disorder, patients with obsessive-compulsive disorder exhibit higher plasma nitrate levels, and drugs useful in obsessive-compulsive disorder influence nitric oxide, we hypothesized that nitric oxide may have some role in obsessive-compulsive behavior. We used marble-burying behavior of mice as the animal model of obsessive-compulsive disorder, and nitric oxide levels in brain homogenate were measured using amperometric nitric oxide-selective sensor method. Intraperitoneal administration of nitric oxide enhancers … significantly increased marble-burying behavior as well as brain nitrites levels, whereas treatment with 7-nitroindazole-neuronal nitric oxide synthase inhibitor (20-40 mg/kg, i.p.) or paroxetine-selective serotonin reuptake inhibitor (5-10 mg/kg, i.p.) dose dependently attenuated marble-burying behavior and nitrites levels in brain…. In conclusion, obsessive compulsive behavior in mice appears related to nitric oxide in brain … [16]

Giving mice arginine, which raises NO levels, reverses the effect of SSRI antidepressants:

enhancement of NO synthesis by l-arginine reversed the effect of SSRI antidepressants, further demonstrating the role of NO in regulating the marble-burying behavior [17]

In rats allowed access to cocaine, blocking NO production decreased their self-administration of the drug. [18] This raises the possibility that Chlamydiae infection, leading to increase NO production, would increase self-administration of cocaine.

So if your pet mice are addicted to cocaine, maybe you should give them antibiotics!

Conclusion

Chronic infections are widespread in both humans and animals, and can have odd effects on behavior and health. Yet researchers have barely begun to detect their existence, much less trace their effects.

I don’t know whether chronic infections were involved in the apparent poisoning of C57BL/6 mice by tryptophan. But, since tryptophan is a very strong promoter of bacterial growth, and bacterial infections trigger interferon gamma and nitric oxide release which can induce ulcerative dermatitis and compulsive behavior in this breed, the possibility can’t be ruled out.

References

[1] Dufour BD et al. Nutritional up-regulation of serotonin paradoxically induces compulsive behavior. Nutr Neurosci. 2010 Dec;13(6):256-64. http://pmid.us/21040623.

[2] Sundberg JP et al. Primary Follicular Dystrophy With Scarring Dermatitis in C57BL/6 Mouse Substrains Resembles Central Centrifugal Cicatricial Alopecia in Humans. Vet Pathol. 2010 Sep 22. [Epub ahead of print]. http://pmid.us/20861494.

[3] Lawson GW et al. Vitamin E as a treatment for ulcerative dermatitis in C57BL/6 mice and strains with a C57BL/6 background. Contemp Top Lab Anim Sci. 2005 May;44(3):18-21.  http://pmid.us/15934718.

[4] Perkins SN et al. Calorie restriction reduces ulcerative dermatitis and infection-related mortality in p53-deficient and wild-type mice. J Invest Dermatol. 1998 Aug;111(2):292-6. http://pmid.us/9699732.

[5] Dawson DV et al. Genetic control of susceptibility to mite-associated ulcerative dermatitis. Lab Anim Sci. 1986 Jun;36(3):262-7. http://pmid.us/3724051.

[6] Andrews AG et al. Immune complex vasculitis with secondary ulcerative dermatitis in aged C57BL/6NNia mice. Vet Pathol. 1994 May;31(3):293-300. http://pmid.us/8053123.

 [7] Boelen E et al. Chlamydia pneumoniae infection of brain cells: an in vitro study. Neurobiol Aging. 2007 Apr;28(4):524-32. http://pmid.us/16621171.

[8] Ikejima H et al. Chlamydia pneumoniae infection of microglial cells in vitro: a model of microbial infection for neurological disease. J Med Microbiol. 2006 Jul;55(Pt 7):947-52. http://pmid.us/16772424.

[9] Moazed TC et al. Murine models of Chlamydia pneumoniae infection and atherosclerosis. J Infect Dis. 1997 Apr;175(4):883-90. http://pmid.us/9086145.

[10] Campbell LA et al. Mouse models of C. pneumoniae infection and atherosclerosis. J Infect Dis. 2000 Jun;181 Suppl 3:S508-13. http://pmid.us/10839749.

[11] de Kruif MD et al. Chlamydia pneumoniae infections in mouse models: relevance for atherosclerosis research. Cardiovasc Res. 2005 Feb 1;65(2):317-27. http://pmid.us/15639470.

[12] Kaiko GE et al. Chlamydia muridarum infection subverts dendritic cell function to promote Th2 immunity and airways hyperreactivity. J Immunol. 2008 Feb 15;180(4):2225-32. http://pmid.us/18250429.

[13] Jupelli M et al. Endogenous IFN-gamma production is induced and required for protective immunity against pulmonary chlamydial infection in neonatal mice. J Immunol. 2008 Mar 15;180(6):4148-55. http://pmid.us/18322226.

[14] Bussiere JL et al. Reproductive effects of chronic administration of murine interferon-gamma. Reprod Toxicol. 1996 Sep-Oct;10(5):379-91. http://pmid.us/8888410.

[15] Roshick C et al. Comparison of gamma interferon-mediated antichlamydial defense mechanisms in human and mouse cells. Infect Immun. 2006 Jan;74(1):225-38. http://pmid.us/16368976.

[16] Umathe SN et al. Role of nitric oxide in obsessive-compulsive behavior and its involvement in the anti-compulsive effect of paroxetine in mice. Nitric Oxide. 2009 Sep;21(2):140-7. http://pmid.us/19584001.

[17] Krass M et al. Nitric oxide is involved in the regulation of marble-burying behavior. Neurosci Lett. 2010 Aug 9;480(1):55-8. http://pmid.us/20553994.

[18] Collins SL, Kantak KM. Neuronal nitric oxide synthase inhibition decreases cocaine self-administration behavior in rats. Psychopharmacology (Berl). 2002 Feb;159(4):361-9. http://pmid.us/11823888.

Fighting Viral Infections by Vitamin C at Bowel Tolerance

Alan Smith’s remarkable recovery from a seemingly fatal infection, discussed here and here, thanks to administration of 100 g/day vitamin C over vigorous opposition from his doctors, highlights both the slow pace of medical progress and the potential benefits of natural healing methods that cooperate with human biology.

The doctors’ adamant opposition to vitamin C treatment is hard to fathom. There is ample clinical experience demonstrating that high doses of vitamin C can help the body defeat viral infections. Moreover, it is among the safest of known interventions.

Vitamin C in Animals

Vitamin C apparently first developed in plants and land animals about 500 million years ago. An ability to synthesize vitamin C has been retained by most land animals and birds. [1]

Over 4,000 species of mammals can synthesize vitamin C from glucose. In good health, mammals synthesize the equivalent in humans of 2 to 13 g/day; under disease or stress, vitamin C synthesis increases up to 100-fold. [2] Under such conditions, vitamin C synthesis may constitute over 90% of glucose utilization – placing a heavy burden on the liver and arguing that vitamin C must have exceedingly important functions in diseased and stressed states.

Three times in mammals – in bats, certain rodents (guinea pigs and capybaras), and the Haplorrhini branch of the primates (containing tarsiers, monkeys, apes, and humans) – the ability to synthesize vitamin C was lost. [1] The loss in the Haplorrhini line was triggered by a retroviral infection about 60 million years ago.

The loss of vitamin C must have had a selective advantage at the time in order to triumph. Whether that selective advantage would still hold today is unknown. Since most Haplorrhini today obtain the human equivalent of 1 to 4 g/day of vitamin C from diet, it’s plausibly the case that any advantage from loss of C synthesis would hold only for those obtaining gram doses of vitamin C through diet or supplements.

Clinical Experience With High-Dose Vitamin C Therapy

A few unconventional doctors have generated most of the clinical experience with high-dose vitamin C therapy.

Fred R. Klenner, a general practitioner from Reidsville, North Carolina, was the pioneer. In the 1940s and 1950s, he found that viral diseases, notably pneumonia and polio, could be cured or greatly improved by intravenous sodium ascorbate of up to 200 g/day. (He favored the pH-neutral sodium ascorbate over conventional acidic versions.) Vitamin C was first isolated in 1932 and first synthesized in 1934, so Klenner was a very early adopter. [3]

Klenner’s maxim was that the patient should “get large doses of vitamin C in all pathological conditions while the physician ponders the diagnosis.” [4]

Irwin Stone and Linus Pauling popularized vitamin C therapies in the late 1960s and early 1970s.

Persuaded by Stone and Pauling, a doctor named Robert Cathcart, who had previously invented an improved artificial hip, began using high-dose vitamin C when he took up general practice in Incline Village, Nevada.

He soon made an interesting discovery:

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]

Cathcart presented this figure showing how various diseases affected vitamin C tolerance:

Over the next two decades, Dr. Cathcart treated over 12,000 patients with high-dose vitamin C. He found that vitamin C “markedly alters the course of many diseases.” [3] In his experience, Dr. the limit of bowel tolerance was a “convenient and clinically useful measure of ascorbate need”:

The maximum relief of symptoms which can be expected with oral doses of ascorbic acid is obtained at a point just short of the amount which produces diarrhea. The amount and timing of the doses are usually sensed by the patient. The physician should not try to regulate exactly the amount and timing of these doses because the optimally effective dose will often change from dose to dose… 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.

Dr. Cathcart found that vitamin C was helpful in combination with antibiotics against bacterial infections:

The effect of ascorbic acid is synergistic with antibiotics and would appear to broaden the spectrum of antibiotics considerably….

A most important point is that patients with the bacterial infections would usually respond rapidly to ascorbic acid plus a basic antibiotic determined by initial clinical impressions. [5]

Unfortunately, vitamin C didn’t help much against fungal infections:

Although ascorbic acid should be given in some form to all sick patients to help meet the stress of disease, it is my experience that ascorbate has little effect on the primary fungal infections. Systemic toxicity and complications can be reduced in incidence. [5]

Overall, Dr. Cathcart’s experience was that benefits of vitamin C therapy could be huge.

The method produces such spectacular effects … as to be undeniable. [5]

It’s Not Easy to Test Vitamin C In Clinical Trials

Cathcart notes:

Either this titration method or large intravenous doses are absolutely necessary to obtain excellent results. Studies of lesser amounts are almost useless. The oral method cannot by its very nature be investigated by double blind studies because no placebo will mimic this bowel tolerance phenomenon. [5]

The Danger of Induced Scurvy

I developed scurvy at the nadir of my own chronic infection, so I pass this from Dr. Cathcart along as a warning:

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. [5]

Anyone with a chronic infection, certain or suspected, should be careful to supplement gram doses of vitamin C.

How Does Vitamin C Work?

Dr. Cathcart’s explanation for the benefits of high-dose vitamin C is that exogenous vitamin C comes with high-energy electrons suitable for transfer to the molecules involved in respiratory bursts:

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. [6]

This explanation would be consistent with cell biology studies showing that vitamin C is consumed rapidly during phagocytosis:

The high concentration of ascorbate in leucocytes and its rapid expenditure during infection and phagocytosis suggests a role for the vitamin in the immune process. Evidence published to date shows an involvement in the migration and phagocytosis by macrophages and leucocytes … [7]

However, other mechanisms have been proposed by which vitamin C may support immunity:

  • Another early view was that vitamin C helps by destroying histamine, which may be produced in excess under conditions of stress. [8]
  • A 2008 paper from Japan points to a third mechanism: that the oxidized form of vitamin C, dehydroascorbate, has strong antiviral activity in vitro. It may be that the benefit from ingesting high-dose vitamin C comes not from the C itself, but from higher levels of its oxidized waste product, dehydroascorbate [9].

The Japanese finding may supply the best explanation for why, in clinical experience, vitamin C is most effective against viral infections. Phagocytic respiratory bursts are more important for bacterial than viral defense.

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.

Safety

Vitamin C is extremely safe. Intravenous doses of 120 g/day given to cancer patients have been well tolerated. [10]

One of the reasons doctors give for avoiding vitamin C is fear that it might cause kidney stones. However, Cathcart believed vitamin C was beneficial for kidney stones:

It is my experience that ascorbic acid probably prevents most kidney stones. I have had a few patients who had had kidney stones before starting bowel tolerance doses who have subsequently had no more difficulty with them. Acute and chronic urinary tract infections are often eliminated; this fact may remove one of the causes of kidney stones. [5]

Veterinarians Aren’t Afraid to Supplement Vitamin C

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. [11]

Conclusion

Based on Cathcart’s testimony, thousands of patients with infectious diseases have benefited from high-dose vitamin C. Although mechanisms are not well understood, vitamin C probably helps along multiple pathways.

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.

Given its safety and the ease of testing its effectiveness, why shouldn’t every seriously ill person try this therapeutic strategy? Is there any good reason NOT to try it for at least a few days to see if it has an effect?

References

[1] “Vitamin C,” http://en.wikipedia.org/wiki/Vitamin_C.

[2] Lewin S. Vitamin C: its molecular biology and medical potential. New York: Academic Press, 1976, p 109. Cited in Ely JT. Ascorbic acid role in containment of the world avian flu pandemic. Exp Biol Med (Maywood). 2007 Jul;232(7):847-51. http://pmid.us/17609500. Full text: http://ebm.rsmjournals.com/cgi/content/full/232/7/847.

[3] Klenner FR. Massive doses of vitamin C and the virus diseases. South Med Surg. 1951 Apr;113(4):101-7. http://pmid.us/14855098.

[4] “Fred R. Klenner,” http://en.wikipedia.org/wiki/Fred_R._Klenner

[5] Cathcart RF. Vitamin C, titrating to bowel tolerance, anascorbemia, and acute induced scurvy. Med Hypotheses. 1981 Nov;7(11):1359-76. http://pmid.us/7321921.

[6] Cathcart RF. A unique function for ascorbate. Med Hypotheses. 1991 May;35(1):32-7. http://pmid.us/1921774.

[7] Thomas WR, Holt PG.  Vitamin C and immunity: an assessment of the evidence. Clin Exp Immunol. 1978 May;32(2):370-9. http://pmid.us/352590.

[8] Nandi BK et al. Effect of ascorbic acid on detoxification of histamine under stress conditions. Biochem Pharmacol. 1974 Feb 1;23(3):643-7. http://pmid.us/4132605.

[9] Furuya A et al. Antiviral effects of ascorbic and dehydroascorbic acids in vitro. Int J Mol Med. 2008 Oct;22(4):541-5. http://pmid.us/18813862.

[10] Riordan HD et al. A pilot clinical study of continuous intravenous ascorbate in terminal cancer patients. P R Health Sci J. 2005 Dec;24(4):269-76. http://pmid.us/16570523. Hoffer LJ et al. Phase I clinical trial of i.v. ascorbic acid in advanced malignancy. Ann Oncol. 2008 Nov;19(11):1969-74. http://pmid.us/18544557.

[11] Andreasen CB, Frank DE. The effects of ascorbic acid on in vitro heterophil function. Avian Dis. 1999 Oct-Dec;43(4):656-63. http://pmid.us/10611981.

Q&A with Fat Head Readers

Tom Naughton, producer and star of Fat Head, has recently been migrating toward PHD. The resistant starch philia that has been sweeping through the ancestral health world got him started, and after experiencing some benefits from resistant starch and then potatoes, Tom decided to go back and read our book. He liked it and reviewed it positively.

Tom invited me to do a Q&A with his readers, who had lots of great questions. Here it is.

Questions and Answers

Jeanne Wallace: “Should we eat a serving of safe starch daily? And must a baked potato be cold in order to be healthful or is room temp okay?”

You should eat a serving of safe starch several times a day – with every meal! No, baked potatoes do not have to be served cold. Room temperature is OK but body temperature or warmer is even better. Make your potatoes enjoyable.

Vlc eater: “Do you recommend PHD for diabetics and prediabetics? If VLC eliminates fasting glucose issues and leads to better glocose levels overall, do you see a problem? Also, is it possible that the self-reported mood issues reported here are a manifestation of mild carb addiction?”

Yes, I do recommend PHD for diabetics and pre-diabetics.

I discussed this question in a previous blog post (“Safe Starches Symposium: Dr Ron Rosedale,” Nov 1, 2011). The basic biology here is that the body’s physiology is optimized for a carbohydrate intake of around 30%. At higher carbohydrate intakes, glucose disposal pathways (such as switching muscle cells from fat to glucose burning) are invoked; at lower carbohydrate intake, “triage” of glucose occurs, reserving it for the brain, and some useful carb-dependent functions are lost. Both extremes are stressful, and in metabolic disorders, both extremes may be difficult to handle.

In diabetes, the body does not dispose of excess carbohydrate properly, so carb intakes above about 30% are harmful. However, all carb intakes of 30% or lower are handled quite well in terms of blood glucose levels. This has been demonstrated in many studies. I like the LoBAG (Low Bio-Available Glucose) diet studies of Mary Gannon and Frank Nuttall, which are quite close to PHD. They tested both 20% carb and 30% carb diets in diabetics, and both carb levels were handled quite well. Here is data from Gannon & Nuttall’s 2004 study of a 20% carb diet (graph is actually from a later paper by Volek & Feinman).

Over a 24 hour period, blood glucose levels were tracked in Type II diabetics on their usual diets (blue and grey triangles) and after 5 weeks on a 55% carb – 15% protein – 30% fat (yellow circles) or 20% carb – 30% protein – 50% fat diet (blue circles):

You can see that on the 20% carb diet blood glucose came close to non-diabetic levels. The same thing happened in later studies of a 30% carb diet.

What happens when diabetics go to very low carb diets, 10% carb or less? The body invokes “triage” mechanisms for glucose conservation under carbohydrate starvation. Among these are hormonal changes including low T3 thyroid hormone and high cortisol. This condition makes fasting problematic and diabetics tend to develop high blood glucose levels in the morning after the overnight fast. Due to high fasting glucose and severe insulin resistance, HbA1c may be elevated by this strategy compared to a 20% or 30% carb diet. Various pathologies, including hypoglycemic episodes, dysregulation of serum fatty acid levels, ketoacidosis, and adrenal dysfunction become more likely. The long-term dangers described in our “zero-carb dangers” series are also present, including a higher risk for some infections, kidney stones, and other ailments.

Evidence that resistant starch helps diabetics also supports the prescription of starchy foods. It’s likely that natural whole foods will be found to be the best source of fiber, and resistant starch in nature is always accompanied by digestible starch.

PHD has generated very good results in diabetics and so, while diabetics might possibly benefit from a slight bias toward lower carbohydrate and higher protein vis-à-vis the healthy, the ordinary version of PHD seems to be very close to optimal for diabetics.

Ben: “Where can I see a very recent photo of you and your wife? (I see the author/advocate’s physical appearance as a data point when considering a proposed approach to nutrition.)”

We haven’t taken many photos lately, but you can see a video of me from January this year at a blog post we did for Dr. Alejandro Junger’s Clean Program. Here’s a look:

Our May Perfect Health Retreat begins next week and we’ll take photos and post them to our blog and social media. Keep an eye out there for up-to-date photos and maybe video.

Allison: “I want to know recommendations of how to use “safe starch” for weight loss.”

Eat it! Getting about 20%-25% of calories as safe starches (30% of calories as carbs) is optimal for weight loss. It’s best to cook them in a batch and save them in the refrigerator until meal time, when you can quickly re-heat them. This is both convenient and generates more resistant starch.

Maggie: “One of my Resting Metabolic Rate test results showed that my fat burning/glucose burning ratio is .98, meaning I burn .98 glucose. I do not burn much fat (a better score would be .85, for example). Does this mean my dietary fat percentage should be lower than Paul’s recommendations for weight loss because my body is a slow fat burner? What can I do to increase my fat burning rate?”

I am not sure what test you took. A standard test to assess fat burning vs glucose burning is the Respiratory Quotient, which is close to 1.0 when burning glucose exclusively and close to 0.7 when burning fats exclusively. But no one gets a number as high as 0.98 at rest, though it can get that high during intense exertion.

At rest, the Respiratory Quotient should approach 0.7, but in the obese it tends to get stuck at maybe 0.85. To enable it to go lower, you want to support mitochondrial health and train yourself to burn fats better. Supplementing vitamin C and pantothenic acid may help, also daily exercise and circadian rhythm entrainment.

Martin: “What’s your opinion on a cyclic-ketogenic diet, with a carb refeed once a week only? Also, does it matter when one eats carbs during a day (e.g. morning vs. evening) and how it is combined with protein and fats?”

I think once a week is too infrequent for carb feeding. I think daily carb feeding is best.

Carbs are best eaten during the daytime in a fairly narrow feeding window. Relative to protein, carbs should be biased later in the feeding window, protein earlier. But both should be eaten together. Just make the first meal a little more protein rich, the last meal a little more carb rich, or follow it with a sweet dessert.

Fritters: “I own your book, but the whole idea of organ meats, bone broth and fish nauseates me. Also, I’ve heard people with AI problems are sometimes fixed by removing nightshades from their diet. In any case, I have an AI problem and am on prednisone all the time, which shoves my blood sugar way up. I’ve felt a LITTLE better on less nightshades, so I want to keep doing that, but I want to eat closer to the Perfect Health diet without gaining too much weight because of the increased blood sugar from the prednisone. What areas do you think I should concentrate on to get closer to perfect health? I’m already avoiding sugars, wheat and crap-oils.”

Yes, it’s true that many people with autoimmune issues benefit from dropping nightshades. In general, autoimmunity originates with foreign compounds entering the body through a leaky gut, which is the same way food sensitivities originate. Nightshade toxins are immunogenic and can easily generate food sensitivities in people with a leaky gut.

PHD with nightshades removed is essentially a Paleo autoimmune protocol.

Prednisone is a drug I don’t like, it suppresses immunity which suppresses symptoms but often worsens the underlying disease – and it has negative side effects as you’ve experienced.

Focus on eating PHD meals in which starches are paired with meats, vegetables, fats, and acids; support immune function with vitamin A (liver, spinach, carrots), vitamin D (sunshine), daily exercise, intermittent fasting, circadian rhythm entrainment, zinc, iodine, and vitamin C; include collagen (bones, joints, tendons in soups and stews) for wound healing and gut barrier integrity.

Teresa Grodi: “My question for Paul is regarding the “Candida Diet”. I know lots of people, especially postpartum women dealing with bad thrush, who are on the anti-candida diet, which prohibits what you would determine “safe starches”. I think I saw in passing that you had some problems with the anti-candida diets, regarding the prohibition of safe starches, and I thought maybe you could elaborate, with an eye to postpartum/breast feeding mothers. I would love to be able to help my fellow mothers.”

Very low-carb diets will flare fungal infections by suppressing antifungal immunity and reducing the population of probiotic bacteria in the gut, which compete with fungi. A balanced diet with 30% carbs is best for candida.

My answer to vlc eater above about why 30% carb is best for diabetes also applies to Candida: you want a well nourished body, including nourishment with glucose, but without an excess that could feed the infection. It’s only carb intakes above 30% that provide that excess. Carb intakes below 30% starve immune function, extracellular matrix maintenance, and mucus production, all of which help defend against Candida.

Eating liver, getting sunshine, intermittent fasting, circadian rhythm entrainment, and eating fermented vegetables are other elements of a good anti-Candida strategy.

Tony: “Dr. Jaminet’s phd proposes safe carbohydrates to replenish daily glucose stores. He proposes safe carbs because of the damaging health effects of grain carbs (except rice). If a subject occasionally (1,2,3 times a week?) consumed bad starches instead of good starches won’t these bad starches still replenish his glucose stores? Won’t the good fats blunt any insulin spike from the bad starches? In other words, phd with bad starches, wholly or partially, occasionally. Would subject’s health still go down the tubes? Would subject gain weight or stall a weight loss?”

Yes, all starches will replenish glycogen (glucose stores). What makes a starch “good” or “bad” (we use the terms “safe” and “toxic”) is not the starch but associated compounds which can be toxic to us.

I can’t say that your health will go down the tubes if you eat bad starches like wheat. Only that they appear to be risky things to eat. They do harm some people. It’s possible that even in people who appear to be unharmed, they do insidious damage. We can’t know for sure, we just think that it’s prudent to avoid wheat.

No, wheat won’t necessarily cause weight gain by itself. It is associated with higher body mass indexes, however, and there may be mechanisms by which it can promote leaky gut which is inflammatory and promotes weight gain. I think it will be slightly easier to lose weight without it.

Lily: “I am sensitive to sugar, and have a huge addiction to it. Starches like white rice tend to raise my blood sugar too much and I end up binging (even if I have it with a fat source). Are there safe starches that I can eat that won’t raise my blood sugar so much? Potatoes seem to affect me the same way white rice does. I would eat potatoes with the peel, or try brown rice, but don’t those have anti-nutrients? Are there starches that are safe for me, a sugar addict with a body that doesn’t handle sugar very well?”

I’ve heard many stories like yours and people are often surprised to find that all of those things clear up pretty quickly on PHD. The pattern:

  1. Binging and cravings and addictive behaviors typically follow starvation, so I’ll guess you’ve been too low carb for too long. Your brain knows your body needs carbs and when it’s available says, “Ah! We’ve found the nutrient we need! Go eat this precious sugar/starch before this rare and vital food disappears!” To fix this, eat PHD levels of carbs. Over time the craving/addiction will go away.
  2. Weight gain from eating carbs usually indicates a leaky gut and a dysbiotic gut flora, such that when you expose your gut to carbohydrates you get inflammation which activates adipose tissue (an immune organ) and causes it to grow. It also relates to the binging, after past starvation your appetite is upregulated temporarily when you get a chance to repair malnourishment.
  3. High blood sugar upon eating starch indicates that (a) you are cooking and eating it incorrectly and/or (b) you lack the gut flora needed for proper glycemic regulation. To fix (a), read this post, and to fix (b), you need more fiber, including some resistant starch, and fermented vegetables.

Above all, you need a balanced, nourishing diet and immune support. See my previous answers to Teresa Grodi and Fritters for some tips. Your mindset should be oriented toward health, not weight. You should accept that an initial weight gain may be “baked in the cake” so to speak, it is already inevitable thanks to past deprivation, accept it and move on to healing yourself and once healed you will be able to re-lose the weight in a natural and healthful way, and reach your goal weight safely.

Carnivore: “My dilemma is when on a VLC diet my blood sugar (A1C test) very good, fasting glucose very high (I am diabetic) When I start some safe starches (tried potatoes and beans) morning fasting glucose excellent – blood sugar throughout the day – way too high after the meals – and even with medication is coming down in a few hours (too slow). So, my question is: how can one determine how much safe starch is safe? (for a female diabetic approaching the retirement age) and what kind of starch: potatoes, beans, sweet potatoes? I assume rice is out of question for diabetics like me.

This is a very common pattern. See my answer to vlc eater above. 20% to 30% carbs is best. If postprandial blood sugars are high, make sure you are cooking and eating starches properly and working on your gut flora with fiber and fermented vegetables.

Chad: “When weight lifting to gain muscle, most experts say you need to consume massive amounts of carbs in order to gain muscle. Then when you wish to slim down you reduce carbs. I prefer paleo style diets and it makes sense, but I also want to lose fat and gain muscle. The instructions to do so seem to directly conflict with the Paleo Diet idea. How do you induce your body to increase muscle size without consuming nothing but carbs only to go LC to get super lean later? Is increased insulin production necessary to increase muscle size? How do you do that and not become insulin resistant? Body builders get huge muscles and super lean all the time on this super high carb/super low carb cycle and its just so confusing.

The main instrument to vary is total calorie intake, and the relationship between calorie intake, periods of fasting, and the timing and intensity of workouts. Macronutrient proportions should be close to PHD ratios at all times, with slight variations synchronized with workout schedule.

High calorie intakes lead to gain of mass (both lean mass and adipose tissue); low calorie intakes lead to slimming (both lean mass and adipose tissue). The type of physical activity you undertake places the focus on a different mass reservoir. When you do intense workouts, you are focusing the body on muscle; you want high calorie intake at this time to promote muscle growth. When you are resting, you are focusing the body metabolically on adipose tissue – at this time you want to fast and reduce calorie intake to promote loss of adipose mass.

Macronutrient ratios should vary toward more fat and carbs when your calorie intake is high (e.g. eat more dessert like foods) and less fat and carbs when your calorie intake is low – in other words, your protein intake should be more stable than your fat and carb intake. But this is something you will do naturally. It doesn’t need to be consciously directed, and it doesn’t need to be extreme. You do need to direct your conscious mind to varying total calorie intake in sync with your workout intensity, and vary your workout intensity.

Work out every day, but vary the intensity, and vary the calories in sync with workload.

Pierson: “Regarding fructose, what is his opinion on foods like fruit, honey, and sweet syrups? While it does make sense to avoid processed industrial anything, what about whole-foods sweeteners?”

A little bit of honey or sweet syrups is OK. I think you’ll find that on low-carb diets without added sugar, your tastes change and very little honey is needed to make foods taste appealingly sweet. If you weighed the honey and calculated how many calories it had, you’d find it was very small. One teaspoon of honey weighs about 6 grams and has about 18 calories, about 9 calories of fructose or 0.4% of daily energy intake. That’s not going to kill you. We recommend getting about 100 calories of fructose daily from all sources, including fruit.

Fruit and berries are excellent foods and not to be avoided. We recommend eating 2-3 pieces of fruit or servings of berries daily.

Charles Grashow: “If LDL-P increases isn’t that bad regardless of the particle size? Larger particles can still get thru the endothelium and become oxidized it just might take longer.”

Yes. The LDL particles get oxidized in the bloodstream and then taken up by white blood cells, activating inflammation and potentially turning them into “foam cells” and assisting formation of atherosclerotic plaques. Endotoxemia (influx of endotoxins from the gut) is usually the biggest driver of LDL particle oxidation. More LDL particles and more endotoxins = more oxLDL reaching white blood cells = more inflammation and faster plaque formation.

Steve Parker MD: “The preface of the Scribner edition mentions your health issues while eating the standard Amercian diet: neuropathy, memory loss, impaired mood, physical sluggishness, and rosacea. You attribute your subsequent scurvy to the very-low-carb paleo diet you adopted to resolve the original issues. Did your personal physician(s) make the diagnoses and say they were diet-related? Uptodate.com says this about rosacea: “The pathways that lead to the development of rosacea are not well understood. Proposed contributing factors include abnormalities in innate immunity, inflammatory reactions to cutaneous microorganisms, ultraviolet damage, and vascular dysfunction.” Your other three SAD-related problems each have easily 10-20 things that can cause them, many of them unrelated to diet. By the way, I enjoyed the book and learned a fair amount from it. Folks eating the standard American diet should be better off switching to PHD.”

My doctor acknowledged the symptoms but was baffled about the cause, as was I. Rosacea was diagnosed by multiple dermatologists. After we optimized PHD my rosacea faded over a period of about 2-3 years. I would not be diagnosed with it today, though at times I still see traces of it.

The memory loss went away during a three month course of antibiotics, taken in the later stages of transitioning from Paleo to PHD.

The things my doctor was clearly able to diagnose were not very helpful to me. For instance, after my VLC and scurvy phase, my belly became bloated and a fairly hard nodule formed which my doctor said was a lipoma. We did a barium enema and it found diffuse diverticulosis. But that was not a cause of my health problems, it was an effect of the VLC-scurvy mistake. I found the various testing we did interesting and educational, but in the end it didn’t show me a path forward. It was diet, lifestyle, and a somewhat speculative round of antibiotics that cleared things up.

Thanks for the praise!

Ryan H: “In your book you explain that fats and acids (ex: vinegar, lemon/lime juice) blunt the insulin spike of starches. To my knowledge you do not mention or recommend cinnamon doing the same. I am just wondering what your take on cinnamon is? I have heard that it lowers blood glucose levels. P.S. Cinnamon on a sweet potato is pretty good!”

Cinnamon is good, but like all good things, it’s possible to get too much. Eating to optimize flavor is a good guide to the optimal amount. I agree, cinnamon and butter on sweet potatoes is delicious!

Mike W: “Do you make any distinction, health-wise, between short-chain saturated fats and long-chain? The reason I ask is that foods heavy in short-chain sat fats (bovine milk, coconut oil, palm kernel oil) seem to give me clogged pores and acne, so I avoid them. This is no hardship for me, I was never big on cheese, butter, or coconut anyway. The fatty foods I do eat – eggs, meat, nuts, chocolate – don’t bother my skin at all, and in my research I’ve found their sat fats are almost exclusively 14-carbons or longer. Besides keeping my skin clear, I can justify my short-chain avoidance from an ancestral standpoint. I doubt my distant ancestors had access to coconuts, and as I understand it, human milk has a lot less short-chain fats than bovine milk. So… are short-chain saturated fatty acids an essential nutrient? Am I missing something by avoiding them?”

Yes, short-chain and long-chain saturated fats are discussed in different chapters of our book because their biological effects are quite different.

I suspect your problem is more related to consuming oils, than to the chain-length of the fatty acids. Try supplementing pantothenic acid, zinc, and choline (or eat egg yolks and liver) and I bet you will tolerate the oils a lot better.

Coconut milk is not an essential food, but it is a healthful one, and we recommend it.

Ryan H: “You advise if one needs to consume something during a fast (for hunger reasons), a spoonful of coconut oil or mct oil is allowed without it hindering the fast. What is your take on butter or cream during a fast (like in coffee)? Will it break the fast and autophagy. I am just wondering since some LC people recommend it and say you are still reaping the benefits of fasting since you’re not consuming protein or carbs.”

Protein disrupts a fast the most, carbs next, fats the least. If you want a bit of cream in your coffee, that’s fine. If you are concerned about its effect on autophagy, delay your breakfast an extra 10 minutes, that will get the lost autophagy back.

Becky: “For the nightshade avoiders among us: Does packaged tapioca starch serve as a resistant starch? If so, can it be eaten like potato starch … in water, raw? I use it to make baked biscuits. Will they, cooled, provide resistant starch? Cassava, sago and taro are not available here. I like to keep rice to a minimum. Plantains, green bananas and sweet potatoes are my starches. I got diverticulitis on VLC and am enormously vested in getting my gut biome fed with resistant starch. I am the Becky quoted in your book, in the thyroid discussion. To update, Hashimoto’s antibodies DISAPPEARED from my TPO blood tests, and my doctor says I no longer have Hashimoto’s. He thinks it was probably giving up wheat.”

Hi Becky, it’s great that your Hashi’s is gone! And thanks for contributing your story to our book!

Detailed questions about resistant starch content of various foods under various cooking methods should be directed to Tim and Grace, who have been researching those things.

I would say however that you should not eat tapioca starch in water raw. Rather, make it into foods like your biscuits and eat them as parts of meals in the PHD manner, accompanied by butter, vinegar, vegetables, and meat. Or at least, as a dessert with butter and vinegar.

Norm: “1. Why do hunger and cravings for carbs increase for some people by introducing rice and potatoes whereas most of the people do not have that being low carb?

2. How do we know that symptoms associated with low carb like cold hands and feet, low thyroid etc are NOT from eating less as hunger is dramatically reduced on a low carb diet?

3. Paul highly recommends 16 hours of fasting, would PHD provide the same benefits especially weight loss without 16 hours of fasting? Probably standard American diet would be a lot healthier with 16 hours of fasting? If calorie restriction is not good or creates problem for people especially in term of weight loss then why calorie restriction is achieved via intermittent fasting on PHD?”

Many people on very low carb diets have hunger and cravings for carbs. Often it gets displaced into a craving for sweets or for alcohol.

For many low-carbers, adding rice and potatoes leads rapidly to a feeling of well being and satisfaction. It quiets appetite.

For others, eating rice or potatoes can trigger strong cravings for more. For reasons why, see my answer to Lily above. There are usually two components to this. First is a need for the body to replenish glucose-dependent proteins such as extracellular matrix; typically this takes at most a few weeks to a month, after which appetite diminishes. Second is an inflammatory reaction from gut pathogens that feed on the carbs. This requires fixing the gut dysbiosis or infections.

The low thyroid is a hormonal reaction to conserve glucose, and associated phenomena like cold hands and feet illustrate the inability of the body to properly maintain homeostasis when it is starved of a key nutrient. As far as reduced appetite on low-carb, there is a difference between reduced appetite due to a body being well nourished, and the anorexic lack of appetite that is induced during chronic starvation. The first is desirable, the second is not.

16 hour intermittent fasting is beneficial for health so long as the 8 hour feeding window falls in the daytime. PHD would still be an excellent (nourishing, low toxicity) diet without intermittent fasting, but this is another opportunity to improve health. Lifestyle is as important as diet for health.

It is not so much that PHD with intermittent fasting restricts calories, it is that it achieves optimal nourishment with the smallest possible caloric intake. In other words, one eats fewer calories without any restriction of nourishment when eating PHD. If this is hard to understand, try reading Chapter 17 of our book.

Gerard Pinzone: “I’m interested in trying this out to see what difference it might make. I’ve heard that there may be an initial period of weight gain. If true, why? Can you provide a recommended schedule? Something like, “1 tablespoon of potato starch in the morning for one week, then increase by 1 tablespoon each week until you reach 4 tablespoons.” Is it better in the morning than night? Also, what issues are signs that we should stop and which should we grin and bear? Can we start/continue to take a probiotic? Should we?”

Coming from SAD, people almost invariably lose weight when adopting PHD. I haven’t heard of any cases of weight gain in people coming from the standard American diet.

Coming from lower-carb diets, the immediate reaction can be either weight loss or weight gain. There are two principal reasons why weight gain may occur. It is partly a matter of low-carbers “adopting PHD” by simply adding starches to their Paleo diet, thus adding calories; and partly a matter of a gut dysbiosis or infection leading to greater inflammation when carbs are added. The solutions are (a) emphasize nutrient density and dietary balance so that hunger abates with lower calorie intake – that is, implement PHD more fully; and (b) address gut health through immune support and fermented foods and fiber.

I recommend just adopting PHD in toto from the beginning. There’s no reason to delay a good thing.

It’s fine to take probiotics but fermented vegetables usually contribute more.

JD says: “Just like all of this rethinking about RS, I’ve been rethinking the theory about optimal omega 3:6 ratios. Everything I remember reading about it recommends the ideal ratio is between 1:1 and 1:4. But what if it’s less about the ratios and more about eliminating bad fats (franken oils, factory farmed animals). Let’s say someone is following the Perfect Health Diet almost to a T, except most of their fat calories are coming from a high quality olive oil so the O3:6 ratio is closer to 1:8; is there any reason to think that person might less healthy than someone with a more ideal ratio? I do remember reading about how essential fatty acids from O3 and O6 fats compete for the same enzymes, but are there any studies out there that suggest excessive olive oil consumption interferes with therapeutic doses of O3 EFAs?

I guess my question could really be simplified to this; Is there any reason I should stop drowning my salads in olive oil?”

Our peak health ranges are about 1% to 4% of calories from omega-6 fats (mainly linoleic acid) and 0.5% to 1.5% of energy from omega-3 fats (mainly from marine sources).

If you eat at the high end of the omega-6 range (4%) and the low end of the omega-3 range (0.5%), you’ll still have perfect health according to our analysis, and you’ll have an 8:1 ratio.

However, you have to hit fatty acid quantities spot on to be the peak health range for both with that ratio. If you have a 3:1 ratio, you could eat omega-6 anywhere from 1.5% to 4% of energy and still be in the peak health range for both. So that is a more desirable ratio to aim for.

Drowning your salads doesn’t sound good. How about flavoring your salads with olive oil?

Amberly: “If using RS as a supplement (ie Potato Starch in a smoothie or cup of warm water), is there a “best” time of day to take it? In the morning? Before bed? All at once? Split into two or three doses?

Also, I am very sensitive to carbs and need to lose quite a bit of weight. What is the lowest number of carbs you would recommend going? Is it possible to stay in ketosis? Can you get the same health benefits from a cyclical ketogenic diet–IE VLC most of the time with one or two evenings a week of safe starches? Can you get health benefits by adding just RS (ie Potato Starch) but not the safe starches?”

Take RS before your first meal. If you do intermittent fasting and your feeding window is 11 am to 7 pm, take the RS at 11 am.

I would recommend getting at least 20% of calories from carbs, but I think 30% is better for most people.

Lower carb diets should be seen as only temporary therapeutic diets, forms of extended fasting, not as permanent diets. Ketosis is fine, unless you have certain infections, but chronic starvation of desirable nutrients is not. I think it’s best to eat starches daily. No, your body needs glucose as well as a healthy gut flora.

Mike G: “I believe you mean the enzyme amylase, rather than lipase? Amylase will hydrolyze the starch into maltose disaccharides first, then maltase (on the villi of the small intestine) will digest the maltoses into glucoses. Then the glucoses can be easily absorbed via transporters on the villi surface. This is why I cannot wrap my head around how fatty acids could blunt glucose spikes, or insulin spikes. Do the fatty acids bind to the glucoses? I suppose they could, given that we have glycolipids on our cell membranes.”

I don’t know what this is referring to. If it’s our recommendation to combine starches with fats in order to reduce their glycemic index, the reason blood glucose is lowered by eating starches with fat has to do with delayed stomach emptying and improved metabolic regulation.

Troysdailybacon: “With regards to Xylitol – I use it as a tooth protocol to fight cavities, but end up injesting a small amount. I’ve heard that it acts like a prebiotic as well. But in the mouth, bad bacteria try to metabolize it, but can’t, so the bacteria die off. How does Xylitol react in the gut? Will it feed the good bacteria and produce butyrate? Or, like in the mouth, will it kill off good and/or bad bacteria in the gut?”

Xylitol like other sugar alcohols can be fermented by some bacteria, and it has antimicrobial effects against others, so it will alter the gut flora (and the oral flora). I am not sure we know enough to say whether the changes are good or bad.

In in vitro studies, xylitol doesn’t seem especially effective at preventing cavities – it doesn’t do nearly as well as fluoride; and it also appears ineffective in human studies. This may be one of those cases where positive early studies don’t seem to be replicable.

Rob: “Do you recommend supplementing with additional resistant starch (potato starch) and other fermentable fibers (inulin, pectin, etc) or just getting these things from food? What are the potential negative effects of too much resistant starch and fermentable fibers?”

I recommend getting fiber from food, but designing one’s diet and preparing food to make it fiber-rich. This can be done by eating natural whole foods, copious fruits and vegetables, and pre-cooking and refrigerating starches.

It is unclear what the negative effects of too much fiber would be, but there is surely a point when you can get too much.

I think of it in ecological terms. You are crafting an ecosystem in your gut, and you want an ecology that favors evolution of a healthful flora.

Humans have an overnight fast of 12-16 hours and a daily feeding window of 8-12 hours. Gut bacteria have a reproductive life cycle of about an hour when food is available. So during your daily feeding, your bacteria have enough food to reproduce and could potentially double their numbers 8 times, or increase their population 256-fold. Then they go through an overnight fast, and their numbers diminish. Ecologically it is a boom-bust cycle similar to deer multiplying when food is abundant and then starving in the winter.

Within the overnight fast, your immune system has an advantage in shaping the ecology. Where probiotic flora are present, it can reward them by generating mucus; where inflammatory pathogens are present, it punishes them with antimicrobial peptides. During the fast, microbes are relatively defenseless due to lack of resources. During feeding, microbes have the upper hand.

Providing lots of fiber creates a boom-bust ecology on a daily cycle, while a low-fiber diet creates more stable bacterial population levels.

In general, you want to eat the amount of fiber that maximizes microbial diversity (that is, genetic diversity) in the gut. Low microbial diversity is associated with disease, high diversity with great health.

Boom-bust ecologies create a different set of selective pressures on bacteria than ecological systems with stable food supplies. Potentially, too great an amount of fiber might reduce microbial diversity by rewarding species that are able to reproduce most rapidly during the food “boom” and preserve their numbers by hibernating during the overnight “famine”. Many beneficial species may not compete successful with hyper-growers like E. coli in such an ecosystem.

Low microbial diversity in the gut is associated with many diseases. Usually low diversity results from starvation of fiber, but conceivably supplementation with large doses of resistant starch could bring about a similar result.

I consider the optimal amount of fiber to still be an open research question. We don’t know the answer. But I am confident the optimal amount is not “infinite fiber.” There will be some amount that is too much.

Incidentally, getting a diversity of fiber types – not just resistant starch – will be important, as this too will promote microbial diversity. This is one reason a natural whole foods approach is likely to be optimal.

TMA: “I haven’t read your book but what I’ve read about your diet on your website sounds appealing. One concern I have though is the number of different supplements you recommend. I’d be leery of low dose lithium for example. Do you discuss your rationale for these supplements in your book? And how would you suggest that people gauge their responses to a given supplement when there are so many and the purported effects are subtle and subjective?”

Yes, we discuss the rationale for supplements in our book. I think if you compare our supplement list to the list of ingredients in a multivitamin, you’ll see that our list is much shorter.

Lithium is a good example. It is one of those compounds we seem to need for optimal health, longevity, and neurological function, yet it is removed from the modern water supply and is depleted in soils by repetitive  annual planting of plants in agriculture. Compounding those environmental reductions is the fact that most people don’t eat many vegetables. So it is easy for a diet to be deficient in lithium.

It’s a good practice to stop supplements entirely for a few weeks every once in a while and see if you feel better or worse without them.

Gabe: “I’ve heard you refer to your own experience in dealing with and/or eliminating chronic infections. Can you offer us some insights or advice on the solutions you found to these chronic infections, and/or what kind of medical practitioner one should consult? If one is already seeing a medical practitioner, what kinds of testing would indicate that practitioner is thoroughly considering what you know to be the right kinds of tests?”

My personal solution was PHD plus antibiotics. I would recommend trying PHD (including the lifestyle advice – intermittent fasting, daily exercise, circadian rhythm entrainment) first and trying antibiotics as a last resort.

Testing is a complex question. The patient’s symptoms provide clues, lab tests provide clues, the practitioner has to understand biology and interpret them. There is no recipe that fits every patient, and you can waste a lot of money on uninformative tests. It’s best to find a clinician with good judgment to help you.

Howard Lee Harkness: “Is the “soluble fiber” in chia seed (gel) a suitable “resistant starch” for the PHD? I’ve been experimenting with chia seed gel, and I have noticed that when I eat a serving (about 3 tbl chia seed soaked in 8 oz water about 15 minutes & added to a 20g protein shake with ice, coconut oil and MCT), I am not hungry again for a very long time (12 hours or more). However, I have not noticed any weight loss over the past week. My other main source of soluble fiber is raw carrot (about 1/2 cup per day), which I’ve been trying for about 3 weeks, again with no change in weight. Background: I easily lost a bit over 100 lbs on an Atkins-style diet starting in late 1999, but have remained weight-stable at roughly 50 lbs over goal (give or take about 10 lbs) since 2002.”

I am not familiar with chia seeds, although I do see that they can help rats with dyslipidemia and fatty liver. You might ask Tim and Grace about their resistant starch content.

Kathy from Maine: “1. Tom said at the end of the post, “Perhaps you’ll be persuaded to eat a potato smothered in grass-fed butter.” From my limited reading of PHD, I took away the message that the plan is higher fat (65%), but that fat should come from what naturally occurs in foods and NOT ADDED to foods, like butter on the baked potato, etc. Did I misread this?

2. I’m confused on the 140 degrees. I thought that after the initial cooking and cooling, it was critical that the food NOT be reheated more than 140 degrees to reap the most resistant starch.

3. PHD recommends approximately 15% protein, which on a 2000-calorie diet would be 300 calories, or just 75 grams of protein. How does this correlate to Phinney & Volek’s advice in “Art & Science of LC Living” (and in a podcast I heard from Phinney) that everyone needs three 30-gram servings of protein daily, for a total of 90 – 100 grams or more in order to trigger protein muscle synthesis? In that book, they showed a table of a weight loss plan for a woman, and it advocated 100 grams of protein through all stages of the weight loss from “induction” through maintenance. Also, Dr. Eades notes in his Lifeplan book that women over 50 actually need more protein than men (and recommends at least 100 grams daily) because women of that age don’t absorb as much of the protein as do the men. I’ve always tried to get at least 100 grams a day. Is that too much, in Jaminet’s thinking? Or is 75 – 100 grams a good ballpark figure?”

The recommended PHD macronutrient ratios are 30% carb, 15% protein, 55% fat.

Yes, most fat should come from natural whole foods, but most people will probably eat 2-4 tbsp per day of oils from cooking oil, salad dressing, coconut milk, butter, and other oils. It’s good to put butter or sour cream on a potato.

Resistant starch starts to melt (become digestible) with cooking above the boiling point of water, and the strongest rise in melting occurs between 60˚C and 70˚C (140˚F and 160˚F). Five minutes of cooking at 70˚C / 160˚F will eliminate nearly all resistant starch. It can take several days of refrigeration to restore the resistant starch content.

However, briefly warming a potato in the microwave will not raise the potato temperature to 70˚C, and will not destroy much resistant starch.

It’s true that if you want to maximize muscle mass, you should eat more protein than 15%. However, if you want to maximize longevity, 15% is a good number.

We actually give a peak health range for protein that ranges up to 150 grams (600 calories) per day. So the Phinney & Volek numbers are compatible with PHD. Where you choose to fall within that range is a matter of personal preference.

I’ve seen no evidence that elderly women need more protein than elderly men. All studies of centenarians show that elderly women eat less protein than men, and they outlive the men. It would be strange if they ate less and lived longer even though they needed more.

Amberly: “In creating the most RS from a SS, does it matter how the item is cooked/cooled? IE does it matter if you bake the potato and then eat it immediately after it has mostly cooled (below 140), or does it form more RS if it is baked/boiled then put in the refrigerator overnight, and then reheated? Same type of idea with rice. Does the longer a food is cooled the more RS it creates, or is it pretty much the same?”

General principles, you don’t want starches to become dehydrated. So use gentle water-based cooking methods like boiling or steaming. If you have an autoimmune disease or food sensitivities, favor cooking them in a pressure cooker.

You don’t need to cook starches for a long time to gelatinize them – just cook them as you would normally – but you do need to cool them for a while if your goal is to form extra resistant starch. Refrigerate them at least overnight, and resistant starch content actually continues to increase through 4 to 7 days of refrigeration.

Daci: “What about green bananas as a safe starch? I really miss them since being on a lchf diet. I like them better than ripe ones. Always have. Any thoughts?”

Eat them! Bananas are a great food, green or yellow.

George: “Big fan of PHD and have been incorporating resistant starch particularly in the form of 4 Tbl of Bob’s Red Mill Unmodified Potato starch. Question: Give the nutritional breakdown of 4 Tbl of Potato Starch (160 calories/40 grams of carbohydrate): do does amounts contribute to the PHD minimum levels of starch 400-600 calories per day if this form of starch bypasses digestion in the stomach and small intestine and instead is largely digested by gut bacteria in the large intestine/colon? Or is it recommended to eat some starch that is not “resistant”? If so, how much of “resistant” and Non-resistant starch should be consumed or does it not matter?”

No, resistant starch does not count as a carbohydrate source. It is a short-chain fatty acid source providing about 1 to 1.5 calories fatty acids per gram. It doesn’t provide any carbohydrates. Of course, it is always accompanied by digestible starch in real foods. Those count as carbohydrates.

Yes, you should always combine resistant starch with digestible starch. In general, I think a natural whole foods approach is going to work out best in the end.

General guidelines, you want about 20-25% of calories as digestible starch from “safe starches,” about 10% of calories as sugars from fruits, beets, carrots, and the like, and about 2% of calories from maybe 30 grams of fiber per day, probably about half from resistant starch naturally formed in “safe starches” and half from a diverse array of fruits and vegetables.

Pam: “You have milk as a not to be consumed. But, what about raw milk? I have been drinking raw goat milk for about a year. And then there is the Milk Cure from the early 20th century. Your thoughts?”

Hi Pam, as we say in the book, milk is in many ways close to the ideal food, but our food production system does not inspire confidence in it. I would say you do need confidence in your dairy farmer, that he uses aseptic procedures to prevent contamination of the goat milk by goat dung (easy to occur, in nature the udders are often contaminated by stool as a means to pass maternal gut microbes to offspring) and keeps his goats healthy. There is a risk of infections such as brucellosis. Overall I am somewhat doubtful of the advantages of habitually drinking even well sourced milk, but I don’t have strong feelings about it. It can be curative for some conditions, though a good diet would also generally be curative of those conditions. Milk is simply an easy way to obtain a good diet.

Fight! (Just kidding)

The Internet is large, everyone’s got opinions, and we could waste a lot of time trading opinions. For that reason I think critics should generally be ignored, if all they have is opinions without any specific (which is to say, constructive) criticism.

However, once in a while it may be educational to see what authors think of their opinionated critics, so I thought I’d offer comments on a conversation between Harry and Tom. Harry in bold, Tom in italic, my commentary in regular font:

[Harry:] Paul’s central thesis (that toxins cause disease, and should therefore be minimised) is a leap of faith.

Paul: That is overstating our thesis. First, our diet is primarily focused on nutrient optimization, not toxin minimization. Toxin reduction is a secondary goal; the idea is that given two equally nourishing alternatives, say wheat or white rice, if there is evidence that one is significantly more toxic than the other (in this case, wheat more toxic than rice), we should avoid that one and get the nutrition from the safer source.

[Harry continues:] If toxins do in fact cause disease (that is, chronic consumption of low doses of toxins; we all know that consumption of high doses makes one very ill…or dead), then it simply does not follow that they should be minimised.

Hormesis in the body occurs in many systems, including the digestive/metabolic systems. It would certainly strike us as strange if we surmised that, since working to exhaustion causes death, then lying prone all day is the best way to avoid death. Similarly, it is strange (although understandable) that one might think that toxins should be avoided at all costs. Just like exposure to bacteria challenges and ultimately strengthens the immune system, so too it is possible that exposure to a certain level of dietary toxins is preferable to a completely ‘safe’ diet.

Paul: We discuss hormesis prominently in the book; see pages 192-193 at the beginning of Chapter 18, Food Toxins. The reason we aren’t concerned about the toxins in vegetables is that the doses are usually at hormetic or inconsequential levels.

[Harry:] The resolution to this question ultimately lies with controlled studies…but given the difficulty of assessing variables in the human diet, this may be a long time coming.

Paul: It is virtually impossible to do controlled studies of low-level toxicity. We are concerned about effects that may take a month or two off an 80 year life. To detect such effects would require an experiment lasting at least 80 years.

[Harry:] In the interim, how about we swear off alarmist diet gurus that demonise foods that have been eaten by humans for centuries…and instead just shoot for a balanced diet that is mostly unprocessed foods? Too boring?”

Paul: I object to the claim that we “demonize” any food. No, we weigh the evidence for each food’s merits and demerits, and find some foods wanting.

Harry’s main objection is to our eschewal of certain foods, such as wheat and soy, which have been eaten by humans for centuries. But is it really alarmist to point out that many people have noticed health improvements from removal of wheat, that the biomedical literature notes many cases of people harmed by wheat consumption, that research is exposing mechanisms by which wheat compounds do harm, that statistically countries that don’t eat much wheat tend to have longer lifespans (especially after correcting for income), and that there is no evidence for the presence of nutrients in wheat that cannot be obtained equally well from our “safe starches”?

In order to maximize the healthfulness of a diet – and finding the maximally healthful diet was the purpose of our book, thus the aspirational name “perfect health diet” – we have to weigh risks, such as the loss of sperm in men eating soy, and the cognitive impairment experienced by people eating tofu, against the benefits of eating a food, assessed in an “opportunity cost” sense against alternative food choices. Soy and wheat, in our judgment, do not pass this test.

[Tom Naughton:] A balanced diet of mostly unprocessed food is exactly what he recommends. As for toxins, he’s quite clear that it’s a matter of “the dose makes the poison.” He describes safe starches as low-toxin foods, not no-toxin foods. So I think you’re more in agreement than not.

Paul: Thank you Tom. Exactly right.

[Harry again:] Yes, of course the dose makes the poison. My point exactly.

Paul’s view is that the dose should always be as low as possible. This is where we are getting into pure hypothetical territory. There is a possibility (one that is reasonable given what we know about hormesis) that a dose of certain toxins somewhat higher than the lowest possible is superior in terms of promoting good health (just as exposure to some bacteria is far better for the immune system than living in a sterile environment).

Paul: Again, a mis-statement of our views. We discuss many cases of toxic foods that we recommend eating. For example, on page 195 we discuss the case of a woman who nearly died from eating raw bok choy. We recommend cooking vegetables to reduce toxicity and eating a variety of vegetables, not the same vegetable every day, to reduce toxin dosage. We don’t say, “eat the lowest possible dose of bok choy,” rather, “eat bok choy in moderation prepared in a way that reduces toxicity.”

[Harry:] As I said, it would be wickedly difficult to determine the optimal levels of dietary toxins using the scientific method, but it is just conjecture to argue that since a high dose of toxicity is bad for health, the lowest possible dose should be recommended. This is a classic case where ‘common sense’ (a priori reasoning and induction) does not necessarily yield the truth…hence the need for empirical testing.

Paul: The same straw man again, we don’t make that argument. More empirical testing is desirable, yes, but we have to make decisions about what to eat on the evidence available now. Harry appears to favor the decision rule, “eat everything until empirical testing convicts it beyond a shadow of doubt,” but we prefer our rule, “weigh the evidence and avoid foods that appear to deliver an excess of harm over help.”

[Harry:] I guess I’m just over people running a contestable notion up the flagpole and passing it off as truth. The history of dietary advice is replete with such ideas, which while superficially attractive, turned out to be fruitless.”

[Tom:] Well, I personally like the idea of running a contestable notion up the flagpole. The passing it off as truth part is a different matter.

Paul: Well said Tom.

Forming contestable hypotheses and evaluating evidence pro and con in order to come to judgments of their truth is science. Many judgments are tentative and subject to later correction. Harry here comes perilously close to rejecting science per se on the ground that scientific judgments might later turn out to be have been mistaken.

On the other hand, if it is only duplicitous judgments and foundationless claims that Harry objects to, his objection does not apply to us. We show our reasoning and cite the evidence that supports our conclusions.

However, Harry’s concern may apply to himself. Is he certain he is not spreading foundationless claims about diet book authors on the Internet?

Thank You!

Thank you, Tom, and Fat Head readers for the opportunity to answer your questions. It’s been my pleasure!

Around the Web; Revisiting Green Meadows Farm

A few months ago we toured Green Meadows Farm; I wrote about it here. Tomorrow, Shou-Ching and I will be there at 3 pm for a casual talk, Q&A session, and book signing. We’ll discuss what evolution tells us about the optimal diet, and the PHD food plate; but mostly we’ll just be chatting with whoever shows up. Green Meadows Farm also has a great farmstand where you can buy organic food of all kinds.

Green Meadows Farm is located at 656 Asbury Street, South Hamilton, MA. Directions are available on their web site.

Also, Jimmy Moore has just informed me that I was voted #4 guest of the year by Livin’ La Vida Low-Carb readers and will be back for “Encore Week” in January. Thanks, LLVLC fans! I’m excited to talk to Jimmy again, this will be a fun interview.

Sometime this month we’re also going to put together a 7-day meal plan for anyone who wants to try our diet for weight loss. But Jay Wright beat us to the punch, sharing the meals that helped him lose 80 pounds in less than eight months.

[1] Music to read by: From Enya:

[2] Interesting posts this week:

Pal Jabekk explores what happens when you can’t utilize glycogen.

The possibility that XMRV, a new human retrovirus, might cause chronic fatigue syndrome has degenerated into a fiasco. Judy Miskovitz, the principal investigator, has been dismissed from the Whittemore Peterson Institute and arrested on charges of stealing her research notes, which WPI claims belong to them. Dr. Jamie Deckoff-Jones, a chronic fatigue sufferer herself, offers her view of the affair.

Emily Deans discusses mitochondrial dysfunction and depression.

NPR notes that the innate food reward system drives kids to eat more carbs than adults. No surprise there: breast milk is 40% carbs, and we know that’s optimal for infants; the optimum for adults is probably significantly lower.

Stephan Guyenet summarizes some new review papers on the food reward theory of obesity. Dr. Srdjan Ostric comments on the role of food reward in obesity.

Jamie Scott, That Paleo Guy, comments on the circadian variability of sun damage risk. What’s the best time of day to go to the beach?

Canadian political philosopher Colin Farrelly quotes Leonard Hayflick in Nature writing that “Prehistoric human remains have never revealed individuals older than about 50 years of age.” Can this be true? Can bones reveal the age of death so precisely?

The New York Times reports that exercise improves memory.

Seth Roberts reports on a rat who favors pate, salmon sashimi, and scrambled eggs. What a lucky rat!

Japan Times reports on Japanese research indicating that beef and pork consumption is associated with colon cancer risk.

Vitamin B12 deficiency can cause skin lesions.

Dienekes points out that African-Americans are losing the genes that give Africans resistance to malaria.

Dr Briffa reports that low-carb diets look good for cancer patients.

Barry Sears discusses how contestants on “The Biggest Loser” eat.

Wired asks if the obesity epidemic could be due in part to over-use of antibiotics.

Cheeseslave reports that intermittent fasting gave her insomnia and belly fat, perhaps because fasting led her to drink alcohol, and alcohol can induce zinc and magnesium deficiencies.

Steph at Midlife Makeover Year found that eliminating fructose, even from fruit, eliminated her eczema.

Dr David Brownstein argues that the optimal sodium intake is 4 to 6 g/day (1.8 to 2.7 tsp salt).

USA Today reports benefits from a ketogenic diet for Parkinson’s patients.

More pregnancies, more health? Reason at FightAging! reports that fetal stem cells can repair the mother during pregnancy.

[3] Cute animals: Odd couple:

Via Yves Smith.

[4] Me and the GAPS Diet at Wise Traditions: Foot in mouth disease?

Dr. Natasha Campbell-McBride, originator of the Gut and Psychology Syndrome (GAPS) diet, has done a tremendous job refining the Specific Carbohydrate Diet and helping a number of people recover from gut dysbiosis. She is also one of the most popular speakers at the Weston A Price Foundation Wise Traditions conferences – deservedly so, from what I was able to see of her talk.

There was a lot of interest among the Wise Traditions attendees in what I thought of GAPS. Many people came up to me to ask about it, and the first question posed in the question and answer session asked what I thought of GAPS. I tried to make the point that there are many pathogens that can afflict the gut and, while GAPS is great for many gut disorders, no single dietary prescription is going to be perfect for all of them. The GAPS prescription of eschewing starches and obtaining carbs from sugary sources like honey is one of those prescriptions: often beneficial in gut disorders, but not always.

A few PHD readers, whose cases are listed on our “Results” page (see Angie and Bella), had trouble on GAPS and were able to fix their problems by adding starches. I suspect their diets had been ketogenic without starches and the ketones were feeding eukaryotic infections; adding starches eliminated the ketone production and helped them overcome the infections.

Apparently I gave the impression – no doubt I mis-spoke in some fashion – that I thought GAPS was a ketogenic diet. Dr. Tom Cowan spoke to me about it soon afterward. Dr. Judy Tsafrir, who uses the GAPS diet in her psychiatry practice, heard about the episode and wrote about it. I wrote a comment on Judy’s post clarifying my perspective.

I’d like to reprint that comment here, so that my attitude toward GAPS can be placed more prominently into the public record. I have the utmost respect for GAPS; with lore derived both from the Specific Carbohydrate Diet and from years of clinical experience by Dr. Campbell-McBride herself and other nutritionists, it is arguably the leading methodology available today for dealing with gut dysbiosis.

Here is my comment from Judy’s site:

Hi Judy,

A few clarifications. It is not starches per se that are protective of the gut, but glucose; this is needed for mucus production, for preservation of the intestinal barrier, and for immune function. It is possible in very low-carb diets, especially if protein intake is limited, to significantly reduce mucus production and impair the integrity of the gut mucosa and barrier.

Both starches and sugars (such as are found in honey, squash, and carrots) are possible sources of glucose. In cases of gut dysbiosis, one wants to avoid foods that feed pathogens. Both starches and sugars can do this.

Some pathogens benefit from fructose, and fructose malabsorption is very common in bowel diseases.

Many pathogens can also benefit from resistant starch, or the branched structures in starch that humans cannot digest. Starchy foods tend to be fiber rich. As such, they are often problematic in bowel disorders.

I often recommend dextrose or rice syrup, which is readily digestible to glucose only, for bowel disorders. This seems to be the safest glucose source.

There is such a diversity of pathogens in bowel diseases, that no single dietary prescription is universally safe. Zero-carb diets are potentially problematic due to glucose deficiency or ketosis that favors certain pathogens; and for any given carb source, there is a pathogen that can flourish on it.

GAPS came up in my talk in response to a question someone asked. I had recently had two people on GAPS diets report that when they added starches, in line with our recommendations, their health improved and they were able to clear lingering gut problems, including fungal infections. Of course I have no idea how faithfully they were following Dr Campbell-McBride’s recommendations; but I think their cases illustrate the points you make in your final two paragraphs. Every pathology is unique, and diets have to be tailored to individual needs.

I am not quite sure what I said, since this was extemporaneous and I haven’t watched the video, but the symptoms those two readers had were ones that tend to develop on ketogenic diets. If they were excluding fructose because it gave them gut symptoms, then their diet could easily have become ketogenic. I do not think that GAPS is ketogenic in general, but in at least those two cases its attempted application seems to have been so.

I have the utmost respect for Dr Campbell-McBride and I am well aware of the many people her diet has helped. I hope no one thinks that I was in any way denigrating her diet or her very valuable work. I was able to attend part of her talk at Wise Traditions and thought it was the most valuable talk I saw at the conference.

Best, Paul

[5] Interesting comments this week:

[6] Not the Weekly Video: Samsung introduces a new sport: “Extreme Shepherding”

[7] Shou-Ching’s Photo-Art:

[8] Weekly Video: Dr Terry Wahls treats her multiple sclerosis effectively with a high-vegetable Paleo-type diet: