Category Archives: Disease - Page 5

Lessons From The Latest Red Meat Scare

Posted by on April 10, 2013 109 comments

I’ve had about ten requests for thoughts on the new paper in Nature Medicine [1] that finds red meat can promote atherosclerosis by a roundabout route: carnitine in the meat is metabolized by gut bacteria into a compound called TMA, which the liver converts to TMAO, which in high doses promotes growth of atherosclerotic plaques.

The same group has done similar studies with other molecules; two years ago the culprit was not carnitine but phosphatidylcholine. [2]

The Scare

Some of the news stories:

It sounds like red meat is dangerous! The best line came from the New York Times:

Lora Hooper, an associate professor of immunology and microbiology at the University of Texas Southwestern Medical Center, who follows the Paleo diet, heavy on meat, exclaimed, “Yikes!”

The Big Picture

The issue here is closely related to one discussed in page 77 of our book:

Protein is not food for us alone; gut bacteria can ferment protein.

Although fermentation of carbohydrates by gut bacteria is usually beneficial, fermentation of protein is not: it generates toxic compounds, including amines, phenols, indoles, thiols, and hydrogen sulfide, which make a foul-smelling stool.

It seems likely, therefore, that high protein intakes are suboptimal for gut health.

When protein is fermented, nitrogen is released, and many nitrogenous compounds are toxic.

The group behind the new research, led by Stanley Hazen, has been looking at another pathway by which bacterial fermentation of meat might be dangerous – the pathway that runs through Trimethylamine. Trimethylamine (TMA) has a simple structure; three methyl groups bonded to a nitrogen atom: N(CH3)3.

Compounds such as choline and carnitine that contain both methyl groups and nitrogen are potential precursors to TMA.

TMA is responsible for the fishy smell of decaying fish. It is highly abundant in fish.

The liver converts TMA into its oxide, TMAO. The Hazen group in a series of papers has argued that higher TMAO levels in blood are associated with atherosclerosis. In a recent paper they assert, “TMAO levels explain 11% of the variation in atherosclerosis.” [3]

So, the equation they are putting together is: fermentation of meat in the gut produces TMA leading to TMAO production which may increase your chance of atherosclerosis by 11%.

Risk is Highly Dependent on the Nature of Your Gut Flora

Here is the key data from the new paper [1]. The “d3” prefix means that the carnitine was labeled with deuterium, an isotope of hydrogen, to help trace its molecular destinations.

In the left panel of part (e), subjects have been fed a steak (eaten in 10 minutes) plus a 250 mg deuterated carnitine supplement – in total, the carnitine equivalent of 1.5 pounds of meat. Deuterated TMAO levels in blood rise to about 1.8 parts per million after 24 hours.

Then subjects are given antibiotics for a week to suppress their gut flora, and fed steak and deuterated carnitine again. On antibiotics, their blood has no deuterated TMAO at all 24 hours after the meal.

In the right panel, 3 weeks after coming off antibiotics to allow gut flora to regrow, subjects are challenged again with steak and deuterated carnitine. Their blood level of deuterated TMAO now exceeds 12 parts per million – 7 times higher than before the antibiotics.

They go on to test the mix of flora in subjects, and show that flora composition is closely correlated with blood levels of deuterated TMAO after consumption of deuterated carnitine. Some types of gut bacteria produce a lot of TMA from food carnitine, others produce little.

So the amount of TMAO entering the blood from bacterial metabolism of food carnitine is highly dependent on the nature of the gut flora. If you kill off normal flora with antibiotics, then eat meat and carnitine, you will get an overgrowth of bacteria specialized to feed on meat and carnitine. That might not be good for you.

The Vegan vs Omnivore Comparison

Food carnitine is far from the only source of blood TMAO. In fact, TMA is a natural breakdown product of choline, one of the most abundant molecules in the body, and the body has evolved an enzyme for converting TMA into TMAO — the gene is FMO3. So we should ask, how much does metabolism of carnitine by gut bacteria affect blood TMAO levels? For that we need measurements of normal TMAO, not just deuterated TMAO.

We can see what that data looks like in a plot comparing blood TMAO levels between vegans and omnivores (panel c of their Figure 2):

These are the TMAO levels normally circulating in the fasting blood of SAD omnivores and vegetarians. As you can see, there’s considerable overlap between the two distributions. 75% of the omnivores had TMAO levels within the same range as 90% of the vegetarians.

So about 75% of omnivores and 90% of vegetarians have normal TMAO levels. What about the 25% of omnivores and 10% of vegetarians whose TMAO levels are elevated?

In panel e, you can see that the enterotype of the gut flora is a much better predictor of blood TMAO levels than whether someone eats meat. Those with high Prevotella, low Bacteroides averaged about triple the TMAO levels of those with low Prevotella, high Bacteroides flora.

So it really is the gut flora that determine blood TMAO levels.

What Drives the Gut Flora?

What determines whether you have the bad gut flora?

The general picture is this. The immune system regulates the number of microbes living in the gut. When levels become high, antimicrobial peptides are released into the gut to kill some off. When levels are low, antimicrobial peptide production is reduced to let microbes multiply.

This means that if the proportion of bacteria who feed on protein, carnitine, and choline is too high, it’s probably because there is insufficient food for the competing bacteria who feed on carbohydrate forms of fiber. If you have a lot of gut bacteria feeding on fiber, there’s no room in the gut for large amounts of bacteria who feed on meat.

So the 25% of omnivores and 10% of vegan/vegetarians with high TMAO levels are probably the people on low-fiber diets – the ones who get their carbs from flour and sugar. On such a diet, the good bacteria are starved and the bad bacteria that produce TMA multiply.

How Does TMAO Produce Atherosclerosis?

The explanation offered by the Hazen group is that TMAO suppresses “reverse cholesterol transport” conceived broadly as the process of migrating excess cholesterol out of macrophages for transport to the liver and excretion in feces via the bile.

Basically, the idea here is:

  1. Atherosclerosis begins with metabolic syndrome, a state characterized by high LDL levels and caused by endotoxemia (high levels of endotoxins entering the body from the gut).
  2. As we’ve discussed (“Blood Lipids and Infectious Disease, Part II,” July 12, 2011), LDL particles have an immune function. They are oxidized by microbial cell wall components. The resulting oxLDL particles are taken up by macrophages, which then present the microbial cell wall components to other immune cells for antibody formation.
  3. Endotoxemia initiates the process of atherosclerosis by (a) poisoning the liver to cause metabolic syndrome which raises LDL levels, and (b) oxidizing LDL – since endotoxins are bacterial cell wall components that can oxidize LDL – and driving the oxLDL into macrophages.
  4. After macrophages have separated the microbial cell wall components from their accompanying LDL particle, the cholesterol and fat have to be exported to keep them from building up in the cell.
  5. If cholesterol and fat cannot be exported quickly enough, the macrophage is injured and becomes a “foam cell.” Disabled foam cells accumulate in specific locations and form atherosclerotic plaques.
  6. TMAO suppresses bile acid creation, reducing the excretion of cholesterol from the body and leading to higher LDL levels and a greater likelihood that macrophages will become foam cells.

If this is true, then TMAO is not intrinsically atherosclerotic. TMAO in blood only becomes atherosclerotic in the context of metabolic syndrome brought on by endotoxemia.

What causes endotoxemia? A dysbiotic flora generated by a diet high in sugar, flour, and omega-6 fats (see our book, pp 220-222).

Conclusion: Lessons Learned

The lessons of this study are:

  1. Don’t eat a high-sugar, high-flour, low-fiber diet.
  2. Do eat natural whole foods that have the kind of fiber we and our probiotic gut flora co-evolved eating; mainly, resistant starch from in-ground starches like potatoes and soluble fiber from fruits and vegetables.
  3. Don’t eat excessive amounts of meat. As we noted in the book, excess protein is available to gut bacteria for fermentation and that produces a number of toxic byproducts.
  4. Do eat PHD levels of meat – one-half to one pound per day. This level of meat consumption will provide healthful and nourishing amounts of protein, choline, and carnitine, and will not cause any harm if accompanied by PHD levels of healthy plant foods.

None of these lessons is new. This study doesn’t overturn any established dietary wisdom. It is just one more piece of data reminding us to eat a balanced diet consisting of the foods we evolved eating – plant as well as animal.

References

[1] Koeth RA et al. Intestinal microbiota metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med. 2013 Apr 7. http://pmid.us/23563705.

[2] Wang Z et al. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature. 2011 Apr 7;472(7341):57-63. http://pmid.us/21475195.

[3] Bennett BJ et al. Trimethylamine-N-oxide, a metabolite associated with atherosclerosis, exhibits complex genetic and dietary regulation. Cell Metab. 2013 Jan 8;17(1):49-60. http://pmid.us/23312283.

 

What Causes Acne? An Overview

Posted by on February 27, 2013 193 comments

I’ve been promising a series on acne and rosacea for almost two years, but I’ve had trouble working up enthusiasm for it. The problem is that Pubmed has 12,966 papers on acne and 2,587 papers on rosacea, most of those papers are of poor quality, and it is painful to sift through the dross in search of gold.

Fortunately, Seppo Puusa, who blogs at the Acne Einstein, has offered to help. Seppo’s a very smart guy and I thought a conversation between us about acne and rosacea might be an interesting way to do the series.  Seppo has just written a book called Clear for Life: Science-Based Natural Acne Treatment Program, which looks like a terrific guide to overcoming acne. In this first post in our acne and rosacea series, Seppo gives us his overview of acne. Here’s Seppo!

Does it ever feel like acne is just maddeningly confusing? That it just comes and goes without making any sense? It’s almost as if acne is not one disease but a combination of many diseases. For example one person gets acne from eating gluten, while another claims she can eat whatever she wants but breaks out every time she uses certain skin care products. A third person puts the blame on stress. Another person said zinc supplements helped her to get clear.

Is there a way to make sense of this, to reconcile all these seemingly separate causes? I believe there is. And in this post I’ll do my best to give you a framework for understanding acne. Something that ties all these seemingly separate causes together and helps you to make sense of your acne.

Deconstructing acne

In Tim Ferris’s latest book The Four Hour Chef he explains how to use deconstruction to learn a new skill. Basically you boil the skill down to its bare essentials. In acne these are inflammation and hormones (insulin to be more specific).

Let me start by explaining the pimple formation process. Looking at what happens in your skin is important because, surprisingly, understanding this helps you to understand how diet, gut issues, stress and other things can cause acne. Acne is more than skin-deep, but it still happens at the skin.

In acne, skin cells produce too much keratin, a protein that’s the key structural component of your skin, hair and nails. In the skin it holds skin cells together. Normally as skin cells die they separate and are pushed out of the hair/skin follicle (I’ll just call this a “skin pore” from now on). But the excess keratin makes it harder for the dead cells to separate so they are shed in larger lumps. [1]

These lumps of dead skin cells can block the skin pore, and this block prevents sebum from flowing out. One study showed that acne-prone skin produces about 3 times more sebum than normal skin [2], though other studies have found somewhat smaller differences [3, 4]. Now this torrent of sebum flows into the blocked pore and has nowhere to go. So the skin pore expands, like what happens when you blow into a balloon. Oxygen content drops in the blocked pore, and this helps the bacterium P. Acnes to thrive in the blocked pore [5]. The rest you probably know: the immune system responds and causes inflammation in the area.

This process has two breakpoints — points at which we can intervene to prevent or lessen acne. These are:

  • Excess keratin production
  • Excess sebum production

Counter either, or both, of these and your chances of getting acne go down dramatically. And here is where inflammation and hormones comes into play. Because research shows that inflammation in the skin and hormonal factors are the key drivers in both excessive keratin and sebum production.

Inflammation

Many people think of acne as bacterial disease, but more than anything it’s an inflammatory problem. Many researchers now believe that inflammation in the skin is the trigger that kicks off the whole process. Studies have shown that inflammation is present in the very earliest stages of a pimple, even before P. Acnes bacteria colonizes the skin pore [6, 7]. Cell culture studies also show that inflammatory cytokines increase both sebum and keratin production [1,8]. Finally, several studies have shown that antioxidants, whether topical and supplemental, can be as effective as benzoyl peroxide or antibiotics in treating acne [5,9]; this is consistent with the inflammatory view because oxidative stress can trigger inflammation.

Hormones

Acne has been conclusively linked to elevated levels of androgens, insulin, and insulin like growth factor 1 (IGF-1). These hormones stimulate sebum production and there’s some research to suggest they also affect keratin production. [1]

The relationship between acne and hormones is quite complicated. Androgens, or male sex hormones, are arguably the primary hormones affecting the skin. It has been shown that acne does not occur in people with inactive androgen receptors in the skin [10].

However, acne patients do not necessarily have higher levels of androgen hormones than people with clear skin. A portion of acne patients seem to have higher levels of some androgen hormones, but this is far from universal. Rather, acne-prone skin seems to be excessively sensitive to androgen hormones.

Insulin and IGF-1 are key hormones in acne. That’s because while androgens mediate lot of the effects on the skin, insulin and IGF-1 are the hormones you have the most control over. I like to call insulin a booster hormone in acne. And where there’s insulin, there’s also IGF-1. That’s why I group these two hormones together. [11]

Insulin and IGF-1 can stimulate sebum production on their own, but they also stimulate the release of androgen hormones from the liver and can increase the skin’s sensitivity to androgen hormones. That’s why studies show low GI diets can help with acne, and why milk can be so bad for the skin. [1, 11]

How sebum production drives antioxidant demand

The skin is the most exposed of all the organs. It’s frequently exposed to UV radiation, ozone from air pollution, bacteria, dust and other ‘inflammatory insults’. So the skin needs constant protection, and that protection comes in the form of antioxidants. In the skin the antioxidants are primarily in sebum. [12]

Research shows a tight correlation between sebum production and vitamin E secretion by the skin [13]. More specifically vitamin E secretion correlates with squalene secretion. Squalene is a fatty acid and a part of sebum. It really looks like the body uses vitamin E to protect squalene in the skin. When squalene oxidizes it turns into squalene peroxide, a highly inflammatory and comedogenic fatty acid. Animal studies show that applying squalene peroxide on the skin causes acne, and the severity of acne is linked to the degree of oxidation of squalene [5].

So the more sebum your skin produces the more antioxidants it requires. There’s good evidence to show that the antioxidant system in acne patients just can’t cope up with this increased demand. For example comparing skin and blood levels of several antioxidants shows significantly lower levels in acne patients than in people with healthy skin. [5, 9]

This is the factor that, I believe, ties together all those seemingly disparate factors that can trigger or relieve acne:

  • Gut problems increase systemic inflammation and deplete antioxidant reserves leading to more acne.
  • Stress triggers the release of neurotransmitters (such as substance P) that can increase inflammation in the skin leading to more acne [1].
  • Diet can induce or relieve inflammation leading to more or less acne. Diet also affects insulin levels.
  • Supplementing with zinc or other nutrients can provide antioxidants which lessen acne [14].
  • Candida and other pathogens in the skin cause local inflammation which can induce acne.

Conclusion

Acne is a very complicated condition and I don’t for one second pretend that this simple framework perfectly explains every case. Individual differences exist, and things get much more complicated when we get down into details. But I do believe it’s a good big picture overview of what causes acne and hopefully clears some confusion surrounding it.

Most importantly, this framework is broadly actionable. It gives you a systematic way to approach acne. Anything you can do to lower insulin and inflammation (both systemic and local in the skin) can help in acne.

Just remember, where there’s insulin there’s oily skin, and where there’s inflammation there’s acne.

References

  1. Ichiro Kurokawa, et al. New developments in our understanding of acne pathogenesis and treatment. Experimental Dermatology. Volume 18, Issue 10, pages 821–832, October 2009. http://onlinelibrary.wiley.com/doi/10.1111/j.1600-0625.2009.00890.x/full
  2. Harris HH, et al. Sustainable rates of sebum secretion in acne patients and matched normal control subjects. J Am Acad Dermatol. 1983 Feb;8(2):200-3. http://www.ncbi.nlm.nih.gov/pubmed/6219137
  3. S-W. Youn, et al. Does facial sebum excretion really affect the development of acne? British Journal of Dermatology. Volume 153, Issue 5, pages 919–924, November 2005. http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2133.2005.06794.x/full
  4. Apostolos Pappas, et al. Sebum analysis of individuals with and without acne. Dermatoendocrinol. 2009 May-Jun; 1(3): 157–161. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2835908/
  5. Whitney P Bowe, Alan C Logan. Clinical implications of lipid peroxidation in acne vulgaris: old wine in new bottles. Lipids in Health and Disease 2010, 9:141. http://www.lipidworld.com/content/9/1/141
  6. Eady E, et al. Is Acne an Infection of Blocked Pilosebaceous Follicles?: Implications for Antimicrobial Treatment. American Journal of Clinical Dermatology. July/August 2000 – Volume 1 – Issue 4 – pp 201-209. http://adisonline.com/dermatology/Abstract/2000/01040/Is_Acne_an_Infection_of_Blocked_Pilosebaceous.1.aspx
  7. Anthony HT Jeremy, et al. Inflammatory Events Are Involved in Acne Lesion Initiation. Journal of Investigative Dermatology (2003) 121, 20–27; doi:10.1046/j.1523-1747.2003.12321.x. http://www.nature.com/jid/journal/v121/n1/full/5601829a.html
  8. Monica Ottaviani, et al. Lipid Mediators in Acne. Mediators Inflamm. 2010; 2010: 858176. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2943135/
  9. Bowe WP, et al. Acne vulgaris: the role of oxidative stress and the potential therapeutic value of local and systemic antioxidants. J Drugs Dermatol. 2012 Jun;11(6):742-6. http://www.ncbi.nlm.nih.gov/pubmed/22648222
  10. J Imperato-McGinley, et al. The androgen control of sebum production. Studies of subjects with dihydrotestosterone deficiency and complete androgen insensitivity. The Journal of Clinical Endocrinology & Metabolism February 1, 1993 vol. 76 no. 2 524-528. http://jcem.endojournals.org/content/76/2/524.short
  11. Melnik BC, Schmitz G. Role of insulin, insulin-like growth factor-1, hyperglycaemic food and milk consumption in the pathogenesis of acne vulgaris. Exp Dermatol. 2009 Oct;18(10):833-41. Epub 2009 Aug 25. http://onlinelibrary.wiley.com/doi/10.1111/j.1600-0625.2009.00924.x/full
  12. Jens J. Thiele, Swarna Ekanayake-Mudiyanselage. Vitamin E in human skin: Organ-specific physiology and considerations for its use in dermatology. Molecular Aspects of Medicine. Volume 28, Issues 5–6, October–December 2007, Pages 646–667. http://www.sciencedirect.com/science/article/pii/S009829970700057X
  13. Mauro Picardo, et al. Sebaceous gland lipids. Dermatoendocrinol. 2009 Mar-Apr; 1(2): 68–71. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2835893/
  14. Dreno B, et al. Multicenter Randomized Comparative Double-Blind Controlled Clinical Trial of the Safety and Efficacy of Zinc Gluconate versus Minocycline Hydrochloride in the Treatment of Inflammatory Acne vulgaris. Dermatology 2001, Vol. 203, No. 2 http://content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowAbstractBuch&ArtikelNr=51728&ProduktNr=227730

A Tale of Recovery from Panic Disorder and OCD

Posted by on January 8, 2013 225 comments

Allison is a nutritional medicine student in Australia whose story illustrates many of our favorite themes – the importance of a healthy ancestral diet and good nourishment; the significance of infections in disease; the value of diagnostic profiling such as stool tests; and the potential value of antibiotics and fecal transplants as therapies for diseases not normally considered to be infectious. Most of all, she shows that in chronic disease, there is always ground for hope. Here’s Allison!  – Paul

When you are convinced that it is raining inside of a bus, sensing the rain drops on your skin, you know that something is very wrong. That was my experience after collapsing at work in London in July 2008, where I had moved in 2007 for the working holiday that’s so much a part of the Australian experience for many young people. After working too hard in my job, I’d picked up a virus which started off as a sore throat and then suddenly escalated to much more. I tried going back to work after two weeks at home resting, but it was to no avail. I had no energy, had trouble standing upright and was so spacey, I felt like I was on another planet – or not on any planet at all.

I’m now writing this from the safety of the other side of what can only be described as a personal hell on Earth. Four years on from that virus, and about ten years after I first started to experience post-viral fatigue episodes, I have finally been given the gift of answers as to what has wreaked so much havoc on my life. I feel incredibly lucky after all this time that the universe has given me answers, when so many people I care about in the online health groups I frequent, don’t seem to be so fortunate. I’m not particularly religious, but getting answers is akin to a miracle.

I’ll backtrack a little to 1999 at age 22 when I had a bout of glandular fever (known as “mono” in the US). I’d watched my elder brother deal with chronic fatigue syndrome in the late 1980s and knew just how bad it could be. It took me about 6 weeks to recover, but I don’t think my health was ever really the same. As a young girl, I was very sporty and academic. But as I got older and I experienced these viruses (to this day I don’t know exactly what virus they were), I was not the same healthy person. I always felt much more tired than other people and was prone to depression, stress intolerance and self-loathing. In the early 2000s, I was able to work full time and had a pretty good social life but I had odd reactions to straightforward procedures like wisdom tooth removal, root canal and vaccinations. Those dental procedures left me feeling flu-like for weeks and the Hepatitis B vaccination needed for overseas travel left me with a large grey patch of raised skin on my inner thigh.  In 2006, things started unravelling for me. After a bad relationship breakup, I picked up yet another virus and felt very dizzy and spaced out. I quickly developed severe muscle weakness and could hardly get out of bed. After about 6 weeks, I returned to work but experienced excruciating headaches and a sudden bout of claustrophobia on a train while commuting to work. In early 2007, I had a repeat of the very same thing for the same length of time. Mum would drive me to the beach for some sea air and I struggled to get my leg muscles to work so I could simply walk on the sand. When I returned to work, I resigned as it was quite a negative environment anyway – except for some of the lovely people I had the pleasure to work with. I was determined that my plans to move to London for a working holiday in mid-2007 would still hold. After “recovering” from that latest bout of post-viral fatigue, I found a contract job so I could save money for my big adventure. The only problem was that at that new job, I developed severe anxiety which left me paralysed at work and wanting to flee – almost all day, every day. My stress tolerance was non-existent. I didn’t seek help at all for the anxiety, I wish I had. Somehow, I managed to make it to the end of that contract and felt proud of myself for getting to the end of it and leaving the project in a pretty decent state for handover. With that, I took off for London.

In London, things were great for the most part but I still had anxiety at work, poor stress tolerance and was pushing myself too hard at work in a less than ideal physical environment – think cramped working conditions with not much fresh air and no air-conditioning. Welcome to modern London! I made it to December 2007 and planned a trip home to escape the London winter, but I developed a serious flu which finally subsided after several weeks but not without making me feel awful and scaring the life out of me. I did well when I was back home for three months and then returned to London again. I only lasted a couple of months before that sore throat I mentioned showed up and kicked off a whole lot of problems.

Literally overnight, I developed about thirty upsetting symptoms that were so bizarre I just couldn’t wrap my head around them. This was not the usual virus and post-viral fatigue episodes I had experienced. It was different. The worst symptoms were:

  • Severe thyroid pain that alternated between stabbing sensations and a vague feeling of pressure
  • Hot and cold body temperature fluctuations, so much so that on a 23C day in London, I could only relieve my body heat by taking a cold bath for half an hour
  • Intense muscle aching around my shoulder and neck region that was only partially helped by holding a bottle of frozen drink to the area
  • I needed to urinate every half hour and every hour overnight – that was quite unpleasant!
  • Constant crying at the drop of a hat. I would call my parents back home in Australia every day and cry. I also saw a couple of health practitioners when I was there (some were doctors, some were “alternative” practitioners such as a naturopath) and I would just constantly cry. Obviously, I was really afraid of what was happening to me, but the crying was excessive
  • I had disturbing thoughts, usually at night time, such as thinking I wanted to jump out of the window of my fifth floor apartment. I also had that very odd experience of rain inside the bus
  • The apartment building also had no lifts, so getting back up to the apartment was a real test of my will, since my legs had stopped functioning
  • I was very dizzy and mentally spaced out
  • Alcohol tolerance was non-existent. During this period, it was my birthday and one of my dear new London friends took me out and I felt so drunk on just a few sips of cider.

The doctors that I consulted during this period were not all that helpful. One was very blunt and told me I had chronic fatigue syndrome and to come back in two months for assessment for a hospital in-patient program. A neurologist I had seen in Sydney in 2007 about my excruciating headaches concluded that since an MRI showed no abnormalities, that my problems were all psychological and I should get myself some Vitamin Z, medico slang for Prozac. He also prescribed Endep for the headaches which didn’t help. Of course, being a crying mess out of frustration and fear from all of these post-viral episodes will typically make a doctor assume the whole thing has a psychological basis.

After two months of no improvement, I had to make the difficult decision to come home to Australia as it represented the best chance I would have to recover, surrounded by supportive family, friends and an environment more conducive to healing. Sorry London, but sunshine and clean air are a necessity for me! I felt like a failure but I knew it was the best choice I could make. I naively assumed I would be back in London in no time at all.

On the flight back home, I couldn’t access the sea salt I’d put in my bag that had successfully resolved the excess urination problem, so that meant I was visiting the plane bathroom every half an hour for almost the entire trip. I wonder what the passengers next to me thought! I got back home to Australia and remember feeling very, very spacey, cold and out of it. I was very relieved to be back home though without the pressures of paying for rent and looking after myself. My Mum to this day has no idea how I made it home on my own and I don’t either. I guess I was just on auto-pilot, desperate to get back home to start healing.

I had pinned all of my problems on thyroid and adrenal issues – this turned out to be partly true, but these were more symptoms of an underlying problem than an actual cause itself. It took me a while to figure that out, which unfortunately was time I could have been treating the foundations with diet and targeted supplementation. I was unable to convince any endocrinologists I’d seen that I had a thyroid problem. All the testing I had (hormone levels plus antibodies) was “normal”, though an ultrasound showed decreased vascularity. They had no explanation for the thyroid pain I had, which incidentally disappeared once I started taking selenium in London. I was diagnosed by a holistic GP with hypothyroidism based on symptoms and started on T4-containing thyroid medication. Every attempt at any medication with T4 in it, synthetic or dessicated porcine thyroid, was a disaster leaving me even worse than off the medication. I’ve been on T3-only medication for a couple of years now and do quite well on it. I was also diagnosed in 2009 with a significant imbalance between levels of zinc and copper but I didn’t understand the implications of that, nor that I’d need to monitor it for life, so I took the supplements prescribed by a GP (general practitioner – the Australian equivalent of an MD) for only three months and gave up.

In late 2009, on Christmas Eve, I was driving back home after visiting a friend and I suddenly had an overwhelming sensation of intense fear wash over me and I thought to myself “I can’t remember how to drive, I have to stop the car and get out”. Time stood still and I desperately wanted to get out of the car and lie down on the median strip. I luckily made it back home but collapsed in a pool of adrenalin. That was the start of the most intense panic attacks you can imagine, something far worse than the anxiety I’d experienced before. I couldn’t drive because the panic was so intense and then the panic was occurring almost all the time – when I was a passenger in a car, on a train, on a bus, riding an escalator in a store, even going for walks in my beloved local park on the bay. I would get a sensation of primal fear and then think I wouldn’t be able to get home safely. Panic attacks were sometimes like a sudden powerful punch to the chest – at other times like a slowly rising tsunami. Home became my safe haven, but I even developed panic attacks at home. I would dread having to leave the house and cry because I hated that this had become my life. If it wasn’t bad enough having the physical symptoms I’d dealt with for years, the panic attacks almost did me in. I could feel agoraphobia approaching quickly and I knew without any doubt that I did not want this to be my life.

Skip to 2011 and things were so bad that I felt at breaking point. I couldn’t see a way out. I was having not just panic attacks but very intrusive thoughts of jumping in front of trains. I was despairing but not suicidal, so these thoughts scared me greatly and I felt I couldn’t trust myself. It made doing normal things that people take for granted almost impossible. I somehow managed to get by with family support, learning mindfulness techniques and breathing exercises. I tried neurofeedback for many sessions and sometimes felt an improvement only to regress again. I was trying to work during this period but it was just not manageable, my sleep quality was at an all time low and I would go to work in a daze, just waiting for the panic attacks to come which they did without fail every day. Having to commute home for an hour added to the problem – thinking about trying to catch the train home in peak hour was just torture. On one occasion, I had to run off a train as it was pulling in to a crowded station as I felt incredibly claustrophobic and fearful. I had somehow managed to complete a Masters Degree in 2010 but it was a struggle to sit in class with all of this going on. I would always sit near the door and didn’t contribute as much as I would have liked during class discussions. Often when I was a passenger in the car my Mum was driving, I would actually get out of the car at traffic lights while the car was stopped because I couldn’t handle being in the car stopped at lights as time stood still for an eternity – it was torture. Trying to rationalise just didn’t work – wherever this fear was coming from, it sure didn’t respond to rational self-talk.

A doctor that I started to see out of desperation in 2011 ordered a Bioscreen test to look at the gut levels of bacterial strains deemed by the researchers who established the lab to be significant in “mystery” ailments like chronic fatigue, behavioural and mental illnesses. Lo and behold, there were a lot of problems that came up on my results – extremely high levels of particular streptococcus strains and non-existent levels of many other bacterial strains considered essential. I had virtually no digestive symptoms at all though. My doctor didn’t really explain the significance of the streptococcus result as it pertains to mental health. I took a 12-day round of erythromycin, felt no different and left that by the wayside. Shortly after, I went to see another doctor that the neurofeedback practitioner worked with and the zinc:copper imbalance came up again and was confirmed as a likely contributor to many of my symptoms. I also had very low levels of B6 according to a Metametrix  organic acids test. My dream recall was non-existent but returned with P5P and B6 supplementation, so I obviously really needed it. I also had an igG subclass deficiency which has now resolved with guided zinc supplementation. Working on the zinc:copper balance has made a big improvement to my health – my immune system is now much more resilient. I haven’t had a post-viral episode for about two years now. I also made the switch to a Paleo diet in early 2011 after getting frustrated with my lack of progress. That has given me a great foundation with which to repair my broken body.

But, I still had panic attacks and increasing agoraphobia which were preventing me from participating in life and making me despair.  I was doing mindfulness and breath work, but they were really no match for it – they helped me cope but only just. Even the mirtazapine I had been taking, which at first was a godsend, had stopped being effective, so I knew I was in trouble. I stumbled on a blog from a fellow Australian called The Power of Poo when I was looking up some information for someone about histamine. In it, the author detailed the connection between streptococcus and mental health. That was a real lightbulb moment. I took this as a sign, so went back to the doctor who had prescribed the erythromycin and asked for two more rounds to see if it would make a difference. The side effects were awful – I felt like I’d been hit by a truck. But after a few weeks, the darkness enveloping me lifted and I felt so much more calm than I’d felt in a long time. I really couldn’t believe it.

Since then, I have re-tested the levels of gut bacteria and taken a few more rounds of erythromycin when I felt the panic attacks returning. I took that to be a sign that the streptococcus was still too high – that was confirmed with the re-testing which showed the streptococcus levels had reduced, but not nearly enough. I still have some episodes of anxiety, but they are nothing compared to the panic attacks I experienced. I am able to do things I had stopped doing – I’m now able to sit through an entire film in a cinema without leaving. I can leave the house without the thought of impending doom stopping me. I am slowly returning to driving but am taking things slow. I feel that the avoidance behaviours that took hold when the panic disorder was at its height need to be addressed somehow, so I try to do some informal exposure, though this isn’t easy when such strong memories are still there. But they are just that – memories.

In 2012, I came across information about a condition that is mostly documented in children and adolescents called PANDAS. The etiology of this condition involves strep throat triggering an immune and neurological response which leads to a range of symptoms including OCD, anxiety, autoimmune complications and excess urination. Bingo! When reading about it, I was convinced that this was what had happened to me. I spoke to one of my doctors about this and he has heard of adults being diagnosed with PANDAS, though there isn’t a lot of awareness of this condition – even less so when it applies to adults and even less so in Australia. My doctor tested my strep titres and one of them was high over range and the other was high in range. This, combined with my history and symptoms was enough confirmation for me. I am considering consulting with an immunologist who recognises PANDAS, though I don’t believe I need a formal diagnosis. I know this is what had tormented me.

I’m now looking at what my options are in the long term as I really do not want to be dependent on antibiotics to keep streptococcus levels under control and endless probiotics to re-populate the bacteria that have been decimated over the years. I’m investigating faecal transplant which has been incredibly successful in Clostridium difficile infections but is not widely recognised as a treatment for much else, especially conditions that are not obvious digestive problems.

Something that I don’t understand that bothers me greatly, is that the medical profession does not currently recognise the link between gut bacteria and mental health. There is acknowledgement that bacteria can cause illnesses such as bacterial pneumonia, endocarditis and rheumatic fever, but there is a gaping hole in the area of mental health and its connection to bacteria. Enlightened health professionals are well aware of this, but the average GP is not. How many people are needlessly suffering and only getting partial relief (if that) with medications? I know from my own experience that if I didn’t get the answer to my situation, I would either be dead, sectioned in hospital or completely agoraphobic and unable to leave my house. I am one of the lucky ones. Lucky that I had a supportive family, lucky that I could get information from the Internet (which often gets an unfair rap from medical professionals) and lucky that in my country, I can access and afford the testing and treatment I need.

I thank my lucky stars every day.

What’s New in the New Edition, 2: How to Lose Weight

Posted by on January 1, 2013 175 comments

NOTE: What’s New in the New Edition, 1 is here; and here is the Amazon book page.

Scribner wanted the new edition to show people how to lose weight. We were happy to do that. I’d been planning to devote 2012 to weight loss and obesity blog posts, and then to write an obesity and weight loss book in 2013. We just moved the schedule up and squeezed the ideas into Perfect Health Diet.

Our book offers a unique take on obesity and weight loss. Some of the science is original to us – the ideas do not appear in Pubmed – and the conclusions are unusual for diet books:

The best diet for weight loss is delicious and does not generate cravings or more than mild hunger. You can – and should! – lose weight with minimal suffering.

The popular diets that generate the quickest short-term weight loss are not optimal for long-term sustainable weight loss; they are prone to yo-yo weight regain.

Unlike those diets, the Perfect Health Diet offers a path to lasting weight less and permanent restoration of normal weight and normal body composition.

If we’re right about the science and these conclusions, then our book could be a game-changer for weight loss.

Filling in Some Missing Context

The major defect of squeezing our obesity & weight loss material into Perfect Health Diet, instead of distributing it over two books, is that we didn’t have space to provide a lot of context to the obesity material. Our stage-setting chapters were devoted to the general question of “what’s a healthy diet” and were framed with a discussion of Michael Pollan’s food rules, not with discussion of issues specific to obesity and weight loss.

So let me add some context here.

The Recipe for a Popular Weight Loss Book

The recipe for a popular weight loss book seems to be:

  • Declare that doltish mainstream authorities are stuck in some absurdly mistaken view, and their loyalty to this paradigm has led them to overlook the key to weight loss.
  • The key to weight loss is simple:  give up a single villainous food.

This formula has been followed to good effect by Dr. William Davis (Wheat Belly) who vilifies wheat, Gary Taubes (Good Calories, Bad Calories and Why We Get Fat) who vilifies carbs in general or sugar specifically, and Dr. Robert Lustig (Fat Chance) who vilifies sugar.

The view that authors attribute to mainstream authorities is, often, a straw man. Here is Gary Taubes in his Reddit “Ask Me Anything” describing the absurdly mistaken view that he calls “calories in, calories out”:

Imagine we have a pair of identical twins. Say 18-year-old boys. Every day we measure their energy expenditure and every day we feed them exactly how many calories they expend. So we match calories in to calories out. They get both the same diet with one exception: one gets 300 calories of sugar or HFCS where the other gets 300 calories of a different carbohydrate or of fat. Then we continue this feeding experiment for the next 20 years or so….

If you believe obesity is about calorie-in-calories-out and that’s the only thing that matters, then both twins are going to end up exactly the same weight with exactly same amount of fat on their body and they’re both going to end up expending the same amount of energy.

The view he is describing is that dietary quality doesn’t matter a whit, only quantity of calories matters: the only thing that affects body weight, fat mass, and energy expenditure is how many calories were consumed, and how many calories are consumed isn’t affected by dietary quality.

In other words, a diet of nothing but cotton candy, Twinkies, and Coca-Cola would generate after 20 years exactly the same body composition and health as a diet of fish, rice, and vegetables.

Is there a single person in the world who holds this view?

Here is a review of Dr. Lustig’s Fat Chance:

The book repeats and expands on the main point of contention in the sugar wars: whether our bodies treat all calories the same. The old guard says yes: A calorie is a calorie; steak or soda, doesn’t matter. Eat more calories than you burn, you’ll gain weight. Lustig believes that our bodies react to some types of calories differently than others. [PAJ: emphasis added]

The “old guard” does not always take kindly to the assertion that it never occurred to them that the body might react differently to different foods. The article notes:

[A] leading endocrinologist, who asked to go unnamed, called Lustig an “idiot.”

These are times when I wish our diet approved of popcorn!

Now, let me be clear: these authors are giving good advice. Indeed, we give the same advice. With Drs. Davis and Lustig, we recommend eliminating wheat and added sugar; with Taubes, we believe the average American should cut carb intake roughly in half. Taking these steps will help people lose weight.

But these books have significant flaws:

  • The advice is incomplete. There are many factors which promote obesity. Removal of a single factor will rarely normalize weight.
  • The scientific background is misleading. It often seems that the goal is not so much to provide insight, as to set up a compelling and entertaining narrative. The story reads like the script of a Hollywood action movie: a frightening and mysterious problem appears which befuddles everyone – a solution is proposed – a hero implements the solution.

Perhaps it is not possible to write books more popular than these, but I think it is possible to write books that provide more insight and have a better chance of delivering lasting weight loss to readers who are willing to invest effort.

Obesity is a complex disorder, and many factors contribute to it. I think we did a fairly good job of addressing many of those factors – enough to enable nearly all readers to lose weight effectively, but also to gain a deeper understanding of obesity and its causes.

The Puzzle of Fatty Acid Ratios

The focus on wheat, sugar, and carbs in the popular diet books ignores what may be the primary cause of the obesity epidemic. In my Q&A with Latest in Paleo readers, I gave six reasons why omega-6 fats promote obesity. Some of these are discussed in detail in the book.

Any explanation for the obesity epidemic should account for the accumulation of omega-6 fatty acids in the body that has coincided with the obesity epidemic:

This is a plot found on p 115 of the book; the data was compiled by Stephan Guyenet of Whole Health Source, the circles are the omega-6 fraction in adipose tissue, and the crosses are the obesity rate among 18-29 year olds. It is hard to make sense of this pattern if omega-6 fats are not causing the obesity epidemic. No carb-centric explanation for obesity will tend to make omega-6 fats accumulate this way. Unlike some of the other weight loss books, we make a good faith effort to explain data like this.

Why Do Low-Carb Diets Work?

The omega-6 accumulation is only one of a number of puzzles that a good theory of weight loss and weight gain should explain. Another is the efficacy of low-carb diets.

If carbs don’t cause obesity, why do low-carb diets promote weight loss?

This issue is explored in chapter 17, where we show reasons why reducing carbs to 30% of energy or less will be beneficial for weight loss, but also why there’s generally little long-term benefit from further reductions in carb intake. Low-carb is good, but very low-carb isn’t better for long-term weight loss.

The Problem of Yo-Yo Weight Loss

Another important puzzle: Why is yo-yo weight loss and regain so common?

Here is Jay Wright’s weight loss history, mentioned in the book at page 184:

Although he had successful short-term weight loss on a number of diets, including very low-carb Paleo, they always made him hungry and sooner or later the weight was regained.

On our diet, Jay reached his normal weight in October 2011. He emailed me a happy new year wish, and remains at his normal weight 15 months later – the first time since college he’s been able to maintain that weight.

Why did our diet normalize his weight permanently without hunger, when other weight loss diets led to hunger and weight regain? That is the primary subject of our chapter 17, and is one of our original contributions to the theory of obesity.

Malnutrition and Weight Gain

We argue that malnutrition is a potent cause of increased appetite and weight gain.

A theme of Weston A. Price’s Nutrition and Physical Degeneration is that pregnancy depletes nutrients in the mother, frequently leading (especially in closely spaced pregnancies) to malnutrition in both mother and child.

If we’re right, then this could be why pregnancies, especially closely spaced pregnancies, tend to produce maternal weight gain.

I got a New Year’s update from Jennifer Fulwiler, another source of a reader report in the book (on p 11). She’s now pregnant with her sixth child, and left a comment noting her much improved health this pregnancy:

I have been following the PHD for this pregnancy. The results have been amazing. In fact, with all five of my previous pregnancies I had debilitating, severe morning sickness. On the PHD, I had almost none!

In an email she gave further details:

My husband and I have a reality show that recently started airing [insert joke here about what we may have done to be deemed “reality show material”], and when the episodes air I’ve been engaging with fans on social media. One of the most common responses I get is that people are shocked that I look so healthy, since I’m pregnant with my sixth child in eight years. A lot of people just assume that women who have many and/or closely spaced pregnancies simply have to be overweight.

I used to assume that too. In fact, that had been my personal experience: I seemed to add a few pounds with each pregnancy, and after I had my fifth child I found myself tired, achy, and 35 pounds overweight. Thanks to the PHD I lost all the weight, and when the show was filmed, in my first trimester of pregnancy with my sixth child, I weighed the same as I did the day I got married, and felt better than I ever had in my life. A lot of people who watched the show asked me what my secret was, and of course I directed them to the PHD!

Here’s the first episode of Jennifer’s reality show:

She does indeed look healthy, energetic, and more than a match for a Texas scorpion!

Conclusion

I mentioned the other day that we got a 4* review at Amazon:

This diet has controlled my cravings. After almost 40 years of interest in and great benefits from proper nutrition, I believe this is as close to perfect eating as we can get…. I didn’t give it 5 stars for two reasons: 1. no recipes…but can get those online and 2. very technical, leaving more explanation or clarification.

That about covers the pros and cons of our book as a weight loss guide. Our story isn’t quite as simple as the other diet books. Perfect Health Diet doesn’t resemble a Hollywood action movie.

But if you want to understand the science and find a successful program for long-term weight loss, we’re the best choice on the market. Perfect Health Diet will eliminate cravings and hunger, get you close to perfect eating, and help you normalize weight for the rest of your life.